B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

Metastatic pattern discriminates survival benefit of primary surgery for de novo stage IV breast cancer: A real-world observational study

IntroductionRole of surgery in the management of de novo stage IV breast cancer (BC) remains controversial. We aimed to determine the survival benefit of primary surgery on the basis of metastatic pattern.Materials and methodsA retrospective cohort study based on the SEER database was conducted to identify patients with de novo stage IV BC diagnosed between 2010 and 2015. Patients were divided into surgery and non-surgery group, and propensity score weighting was used to balance clinicopathologic factors between groups.ResultsOf 8142 de novo stage IV BC patients, 1891 (23%) cases were managed with surgery and 6251 (77%) cases were managed without surgery. There were 3821 all-cause deaths and 3291 BC specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 54.5%, compared to 47.7% (P < 0.001) for the non-surgery group. The magnitude of the survival difference with surgery was significantly correlated with metastatic patterns (P_interaction<0.05). Significant survival improvements in surgery group compared with non-surgery group were observed in patients with bone-only metastasis (adjusted HR = 0.83, P < 0.05) or multiple metastases with bone involved (adjusted HR = 0.76, P < 0.05), whereas survival inferiority of surgery was found for patients with multiple visceral organs-only metastases (adjusted HR = 2.08, P < 0.05).ConclusionThe survival benefit offered by surgery for de novo stage IV BC varies by metastatic patterns. Decisions for primary surgery of de novo stage IV BC patients should be tailored according to metastatic pattern.     

Ultrasound staging in breast cancer: A decision-making oriented approach to axillary metastatic burden prediction

PurposeThe possibility of avoiding axillary lymphadenectomy (AL) in patients with breast cancer (BC) after positive sentinel lymph node biopsy (SLNB) and low metastatic burden (< ó = 2 positive lymph nodes) has put into question the role of axillary ultrasound due to the risk of overtreatment after positive axillary lymph node biopsy with low metastatic burden. Our aim was to identify clinical and ultrasound features to detect low and high metastatic burden.MethodsA retrospective study of 405 BC patients with primary surgical treatment with axillary ultrasound examination and subsequent AL after positive fine needle aspiration (FNA) or SLNB. The low and high tumor burdens after AL were correlated with clinical and ultrasound variables: lymph node morphology (UN1 to UN5), number of suspicious lymph nodes, and Berg level.ResultsPositive FNA, lymph node morphology UN4 (focal thickening with displacement of the fatty hilum) or UN5 (complete replacement of the fatty hilum) and >2 suspicious lymph nodes were significantly associated with "high metastatic burden". Lymph node morphology UN2 and UN3, even after FNA+, lymph node morphology UN4 after FNA-, and suspicious lymph nodes at Berg level I were low metastatic burden criteria. Lymph node morphology UN5, lymph node morphology UN4 after FNA+, two nodes or more with UN4/UN5 morphology, and suspicious lymph nodes at Berg levels II and III with FNA+ were associated with high metastatic burden.ConclusionsAxillary lymph node ultrasound data for patients with early BC allows predicting the axillary metastatic burden, guiding the optimal clinical management of the axilla.     

Association of Apatinib and Breast Cancer: A systematic review and meta-analysis

BackgroundBreast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC.MethodsStudies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I²) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests.ResultsA total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35–1.52, I² = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51–2.13, I² = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups.ConclusionsOur study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.     

Clinical Updates for Colon Cancer Care in 2022

Colon cancer needs better screening and treatment options. Its incidence in the young population is rising. Recent changes in guidelines recommend beginning screening for colon cancer at the age of 45. Circulating tumor DNA presents an opportunity to select patients for administration of adjuvant chemotherapy. Immunotherapy is an option for patients with a deficiency in mismatch repair proteins. However, its efficacy outside of this group of patients remains a challenge. Targeted therapies such as BRAF inhibitors are an option for patients with poor prognosis, for whom cytotoxic chemotherapy is not as effective. This review presents the recently published evidence regarding screening and treating patients with colon cancer.     

Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of Economic Evaluations

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.     

Prognostic factors in patients with oligometastatic breast cancer – A systematic review

AimOligometastatic breast cancer (OMBC) is a disease-entity with potential for long-term remission in selected patients. Those with truly limited metastatic load (rather than occult widespread metastatic disease) may benefit from multimodality treatment including local ablative therapy of distant metastases. In this systematic review, we studied factors associated with long-term survival in patients with OMBC.MethodsEligible studies included patients with OMBC who received a combination of local and systemic therapy as multimodal approach and reported overall survival (OS) or progression-free survival (PFS), or both. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of each included study. Independent prognostic factors for OS and/or PFS are summarized.ResultsOf 1271 screened abstracts, 317 papers were full-text screened and twenty studies were included. Eleven of twenty studies were classified as acceptable quality. Definition of OMBC varied between studies and mostly incorporated the number and/or location of metastases. The 5-year OS ranged between 30 and 79% and 5-year PFS ranged between 25 and 57%. Twelve studies evaluated prognostic factors for OS and/or PFS in multivariable models. A solitary metastasis, >24 months interval between primary tumor and OMBC, no or limited involved axillary lymph nodes at primary diagnosis, and hormone-receptor positivity were associated with better outcome. HER2-positivity was associated with worse outcome, but only few patients received anti-HER2 therapy.ConclusionsOMBC patients with a solitary distant metastasis and >24 months disease-free interval have the best OS and may be optimal candidates to consider a multidisciplinary approach.     

Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic

BackgroundBrain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC.MethodsWe reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models.ResultsAlthough limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8⁺ infiltration were found in brain metastases compared with matched NSCLC primary tumors, suggesting an immunosuppressive microenvironment in the brain. Reactive astrocytes and tumor associated macrophages are paramount in NSCLC brain metastases and play a role in promoting tumor progression and immune evasion.ConclusionsDiscordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.     

BCG Administration after Prior Radiation Treatment for Prostate Cancer

IntroductionProstate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. The underlying mechanism is incompletely understood but is thought to be related to an altered microenvironment promoting tumorigenesis. However, there is a gap in the literature regarding how the effect of BCG varies according to prior radiotherapy in patients with non–muscle invasive bladder cancer (NMIBC). In this context, we sought to evaluate oncologic outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy.MethodsThis is a retrospective cohort study that includes all patients who received intravesical for NMIBC at our institution from 2001 to 2019. Patients were stratified into 3 cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). The outcomes of interest were recurrence at 1-year, progression to muscle-invasive bladder cancer (MIBC), and progression to metastatic disease. Comparisons were also made between cohorts with respect to elapsed time from radiation therapy. Wilcoxon rank-sum test was used for comparing continuous variables, while χ² and Fischer's exact tests were used to examine categorical variables.ResultsIn 199 total patients who underwent BCG for NMIBC, 23 had a prior history of prostate radiotherapy treatment, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at 1 year. There was no difference in the number of induction or maintenance BCG administrations received between the cohorts within the first year. There was no significant difference in recurrence at 1 year between the 3 cohorts (P = .56). There was also no difference in progression to MIBC or progression to metastatic disease with P = .50 and 0.89, respectively.ConclusionThe risk of recurrence after induction BCG treatment for high-grade NMIBC does not vary according to prior radiation treatment for prostate cancer.     

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study

BackgroundTrifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.MethodsFrom October 2020 to February 2022, patients with metastatic colorectal cancer who failed from 2 or more lines of prior therapy and treated with TAS-102 monotherapy, in combination with bevacizumab or immune checkpoint inhibitors (ICIs) were analyzed. The evaluation indicators were progression free survival (PFS), objective response rate , disease control rate (DCR), overall survival (OS) and drug toxicities.ResultsA total of 70 patients were enrolled. The objective response rate and DCR were 1.4% and 68.6%. The median PFS and OS were 6.0 (95% CI: 4.1-7.9) and 10.0 (95% CI: 8.3-11.7) months. Compared with TAS-102 monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab obtained superior DCR (75.9% vs. 50% vs. 40%, P = .047), PFS (6.3m vs. 3.0 m vs. 3.0 m, P = .041) and OS (12.0 m vs. 6.5 m vs. 6.0m, P = .013). Patients without prior regorafenib or fruquintinib therapy obtained better median PFS (6.3 vs. 4.3 m, P = .031) and OS (NR vs. 9.0 m, P = .036). Other indicators, including age, tumor site, KRAS status and use of fluoropyrimidine as last regimen before TAS-102, did not affect the clinical efficacy of TAS-102. The most frequent adverse events were leukopenia, neutropenia, anemia, fatigue, nausea, and vomiting.ConclusionIn real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.     

Clinical Utility of Genomic Recurrence Risk Stratification in Early,Hormone-Receptor-Positive,Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Real-World Experience

BackgroundRNA-based genomic risk assessment estimates chemotherapy benefit in patients with hormone-receptor positive (HR+)/Human Epidermal Growth Factor 2-negative (ERBB2-) breast cancer (BC). It is virtually used in all patients with early HR+/ERBB2- BC regardless of clinical recurrence risk.Patients and methodsWe conducted a retrospective chart review of adult patients with early-stage (T1-3; N0; M0) HR+/ERBB2- BC who underwent genomic testing using the Oncotype DX (Exact Sciences) 21-genes assay. Clinicopathologic features were collected to assess the clinical recurrence risk, in terms of clinical risk score (CRS) and using a composite risk score of distant recurrence Regan Risk Score (RRS). CRS and RRS were compared to the genomic risk of recurrence (GRS).ResultsBetween January 2015 and December 2020, 517 patients with early-stage disease underwent genomic testing, and clinical data was available for 501 of them. There was statistically significant concordance between the 3 prognostication methods (P < 0.01). Within patients with low CRS (n = 349), 9.17% had a high GRS, compared to 8.93% in patients with low RRS (n = 280). In patients with grade 1 histology (n = 130), 3.85% had a high GRS and 68.46% had tumors > 1 cm, of whom only 4.49% had a high GRS. Tumor size > 1cm did not associate with a high GRS.ConclusionGenomic testing for patients with grade 1 tumors may be safely omitted, irrespective of size. Our finds call for a better understanding of the need for routine genomic testing in patients with low grade/low clinical risk of recurrence.     

Establishing and validating predictive nomograms for lateral pelvic lymph node metastasis in patients with rectal cancer based on radiologic factors and clinicopathologic characteristics

IntroductionIt is critical to accurately predict the occurrence of lateral pelvic lymph node (LPN) metastasis. Currently, verified predictive tools are unavailable. This study aims to establish nomograms for predicting LPN metastasis in patients with rectal cancer who received or did not receive neoadjuvant chemoradiotherapy (nCRT).Materials and methodsWe carried out a retrospective study of patients with rectal cancer and clinical LPN metastasis who underwent total mesorectal excision (TME) and LPN dissection (LPND) from January 2012 to December 2019 at 3 institutions. We collected and evaluated their clinicopathologic and radiologic features, and constructed nomograms based on the multivariable logistic regression models.ResultsA total of 472 eligible patients were enrolled into the non-nCRT cohort (n = 312) and the nCRT cohort (n = 160). We established nomograms using variables from the multivariable logistic regression models in both cohorts. In the non-nCRT cohort, the variables included LPN short diameter, cT stage, cN stage, histologic grade, and malignant features, and the C-index was 0.930 in the training cohort and 0.913 in the validation cohort. In the nCRT cohort, the variables included post-nCRT LPN short diameter, ycT stage, ycN stage, histologic grade, and post-nCRT malignant features, and the C-index was 0.836 in the training dataset and 0.827 in the validation dataset. The nomograms in both cohorts were moderately calibrated and well-validated.ConclusionsWe established nomograms for patients with rectal cancer that accurately predict LPN metastasis. The performance of the nomograms in both cohorts was high and well-validated.     

Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

BackgroundGallbladder cancer (GBC) is a rare and fatal biliary tract malignancy. Genetic derangements are one of many factors that determine the prognosis of GBC. In this study, the expression of the stratifin (SFN) gene encoding 14-3-3 sigma protein, which is reported to be associated with the metastatic property of cholangiocarcinoma cells, was investigated in GBC.Material and methodsFormalin-fixed paraffin-embedded cancer (n = 37) and non-cancer control tissues (n = 14) of gallbladders from patients who underwent surgical resection from January 2006 to May 2015 were retrieved. The expression of SFN normalized with that of ACTB was determined using RT-qPCR. Multivariate analysis of factors affecting disease-free survival (DFS) and overall survival (OS) including the type of SFN expression was performed.ResultThe average expression level of SFN in cancer was higher than that in control tissues (p = 0.002). The relative SFN expression in cancer tissue was classified as overexpression (n = 14) and control level expression (n = 23) according to the receiver operating characteristic (ROC) curves for discriminating early GBC recurrence or metastasis after surgery. The SFN overexpression group was associated with lower rates of distant metastasis and early tumor recurrence following resection. The univariate analysis demonstrated factors affecting DFS, including resection margin (p < 0.001), lymphovascular invasion (p = 0.040), perineural invasion (p = 0.046), and SFN expression (p < 0.001). The multivariate analysis revealed that the resection margin (p = 0.019) and SFN expression (P = 0.040) were independent prognostic factors of DFS.ConclusionTo achieve the longest survival, margin-free resection is recommended. The overexpression of SFN in GBC is associated with better prognosis, lower rates of early cancer recurrence, and distant metastasis following resection. SFN expression might be a novel prognostic biomarker in GBC treatment. Further studies to elucidate the role of SFN might unveil its clinical benefit in cancer treatment regimens.     

Snapshots of lymphatic pathways in colorectal cancer surgery using near-infrared fluorescence,in vivo and ex vivo

IntroductionIndocyanine green (ICG) fluorescence imaging has been used for blood flow assessment in anastomoses in the field of colorectal cancer surgery. However, whether ICG fluorescence is related to the presence of cancer cells in the lymph nodes is unclear. We explored the utilization of ICG fluorescence in colorectal cancer surgery.Materials and methodsICG was injected into the submucosa around the tumor before radical resection in colorectal cancer patients. Intraoperatively, near-infrared (NIR) fluorescence was used for lymphatic flow visualization. After specimen removal, harvested lymph nodes were classified as positive or negative based on the detection of fluorescence, followed by pathological examination. ICG distribution on a section of each lymph node was examined by fluorescence microscopy.ResultsOverall, 155 patients underwent real-time NIR fluorescence imaging-guided surgery. Altogether, 1,017 lymph nodes were retrieved from these patients. Metastatic lymph nodes were present in 36 (5.8%) of 622 fluorescence-negative lymph nodes, which was significantly higher than 11 (2.8%) of 395 fluorescence-positive lymph nodes (odds ratio: 2.15, P = 0.03). Fluorescence microscopy of metastatic lymph nodes showed that ICG fluorescence was present in the normal structural region but not in the cancerous region of the lymph nodes. Furthermore, ICG fluorescence was observed in all metastatic lymph nodes, except those with cancer cells occupying >90% of the total area.ConclusionsICG fluorescence detected only the normal parts of the lymph node draining from the peritumoral area and not the cancer tissues. This finding is important for developing appropriate strategies for navigation surgery using NIR fluorescence.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Relationship Between Breast Density,Breast Cancer Subtypes,and Prognosis

BackgroundIn the United States, Europe, and Asia, a consensus has been reached that there is a higher risk of breast cancer in high density breasts. However, there are some contrary reports that suggest the absence of an association between breast composition and breast cancer subtype; thus, there is conflicting evidence. The purpose of this study was to investigate trends in the incidence of breast cancer subtypes according to breast composition and analyze the survival rates in Japanese women.Patients and MethodsBetween 2007 and 2008, 1258 Japanese patients with invasive breast cancer who underwent mammography and obtained a pathological diagnosis in our institution were included in the study. We compared cancer subtypes with breast composition types (dense and non-dense breast), and classified them based on initial mammography findings. Information on 5- and 10-year survival rates was collected by chart review for patients with dense and nondense breasts. Statistical analysis was performed using the Pearson's chi-square test for breast composition and cancer subtype. The effect of breast composition on mortality was examined using a multivariate Cox proportional hazards model, and adjusted hazard ratios were calculated.ResultsNo significant difference was found between breast cancer subtype and breast composition (P = .08). Five-year (log-rank test, P = .09) and 10-year (log-rank test, P = .31) survival rates were not significantly different between breast composition types.ConclusionThere was no significant association between breast composition and cancer subtypes. There was also no significant difference in the prognosis between patients with and without dense breasts.     

Independent risk factors for lymph node metastasis in 2623 patients with Non–Small cell lung cancer

Purposethis study attempts to identify the independent risk factors that can predict lymph node metastasis for the patients with non-small cell lung cancer (NSCLC), and guide doctor adoption of individualized treatment for such patients.Materials and methodsThis study was approved by the Hospital's Ethics Committee and all patients had signed informed consent forms. We retrospectively reviewed NSCLC patients who had undergone surgical resection from December 2008 to December 2013.The statistical significance of evaluation variables and lymph node metastasis was determined with Pearson's Chi-square test. The risk factors of lymph node metastasis were determined through univariate and multivariate logistic regression analysis. And for the age and tumor diameter factors, optimal cutoff points were determined with a receiver operating characteristic analysis.ResultsIn the present study, a total of 2623 patients were included in the study, and 779 patients with lymph node metastasis. Three independent risk factors were identified: age, tumor diameter and Ki-67 index. We found that <65 years of age (Adjusted-OR:1.921), ≥2.85 cm of tumor diameter (Adjusted-OR:3.141), and 5%~25% in Ki-67 group (Adjusted-OR:2.137),≥25% (Adjusted-OR:3.341) were significant. Also we found that 307 patients with lymph node metastasis and the lymph node metastasis rate was 51.0%, when the age<65 years, Ki-67 index≥25%, and the tumor diameter≥2.85 cm. On the contrary, there were only 2 patients with lymph node metastasis, and the rate of lymph node metastasis was 5.1%.ConclusionIdentifying three independent risk factors that predict lymph node metastasis in non-small cell patients, Among NSCLC patients in whom all three predictors were identified, and over a half of the patients showed lymph node metastasis.     

Concurrent High PD-L1 Expression and CD8+ Immune Cell Infiltration Predict PD-1 Blockade Efficacy in Advanced EGFR-Mutant NSCLC Patients

ObjectivesThe effectiveness of PD-1 blockade therapy in advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is limited. We investigated whether patient characteristics, PD-L1 expression, and immune cell (IC) status in the tumor microenvironment (TME) were associated with PD-1 blockade therapy outcomes.Materials and methodsWe retrospectively reviewed patients with advanced EGFR-mutant NSCLC treated with PD-1 blockade (nivolumab or pembrolizumab) between January 2016 and March 2018. The PD-L1 expression tumor proportion score (TPS) and types and distribution of ICs (CD8, PD-1, CD204, tumoral, and stromal) in the TME were analyzed.ResultsAmong 57 EGFR-mutant NSCLC patients treated with PD-1 blockade, 39 patients had sufficient tissues for analyzing the TME. The overall response rate (ORR) of PD-1 blockade was 12.3%. Only tumoral CD8 positive (CD8⁺) IC status was significantly associated with the response (median tumoral CD8⁺ICs: 299/mm² vs. 115/mm², P < .01). Among the 6 patients with concurrent high PD-L1 expression (TPS: ≥ 50%)/high tumoral CD8⁺ ICs (≥ 205/mm²), 5 (83.3%) showed a response and a significantly longer progression-free survival (PFS) (PFS: 9.4M vs. 1.8M, P < .01). In contrast, none of the 7 patients with high PD-L1 expression/low tumoral CD8⁺ICs (<205/mm²) showed a response.ConclusionConcurrent high PD-L1 expression and high tumoral CD8⁺ ICs could predict the response and longer PFS of PD-1 blockade therapy in EGFR-mutant patients.     

Study protocol for the OligoMetastatic Esophagogastric Cancer (OMEC) project: A multidisciplinary European consensus project on the definition and treatment for oligometastatic esophagogastric cancer

BackgroundA uniform definition and treatment for oligometastatic esophagogastric cancer is currently lacking. However, a comprehensive definition of oligometastatic esophagogastric cancer is necessary to initiate studies on local treatment strategies (e.g. metastasectomy or stereotactic radiotherapy) and new systemic therapy agents in this group of patients. For this purpose, the OligoMetastatic Esophagogastric Cancer (OMEC) project was established. The OMEC-project aims to develop a multidisciplinary European consensus statement on the definition, diagnosis, and treatment for oligometastatic esophagogastric cancer and provide a framework for prospective studies to improve outcomes of these patients.MethodsThe OMEC-project consists of five studies, including 1) a systematic review on definitions and outcomes of oligometastatic esophagogastric cancer; 2) real-life clinical scenario discussions in multidisciplinary expert teams to determine the variation in the definition and treatment strategies; 3) Delphi consensus process through a starting meeting, two Delphi questionnaire rounds, and a consensus meeting; 4) publication of a multidisciplinary European consensus statement; and 5) a prospective clinical trial in patients with oligometastatic esophagogastric cancer.DiscussionThe OMEC project aims to establish a multidisciplinary European consensus statement for oligometastatic esophagogastric cancer and aims to initiate a prospective clinical trial to improve outcomes for these patients. Recommendations from OMEC can be used to update the relevant guidelines on treatment for patients with (oligometastatic) esophagogastric cancer.     

Chronic lymphocytic thyroiditis protects against recurrence in patients with cN0 papillary thyroid cancer

BackgroundChronic lymphocytic thyroiditis (CLT) frequently coexists with papillary thyroid carcinoma (PTC) that exhibits normal thyroid function. However, few studies have investigated the relationship between CLT and clinically lymph node (LN)-negative PTC. The aim of this study was to evaluate the relationship between subclinical central LN metastasis and CLT, and to assess the impact of CLT on the recurrence of clinically LN-negative PTC.MethodsWe investigated the medical records of 850 patients with PTC who underwent prophylactic bilateral central neck dissection as well as total thyroidectomy between 2004 and 2010; the median follow-up time was 95.5 months (range, 12–158 months).ResultsCLT was observed in 480 patients (56.5%). Female sex, a preoperative thyroid-stimulating hormone level >2.5 mU/L, a primary tumor ≤1 cm, no gross extrathyroidal extension, high number of harvested LNs, low number of metastatic LNs, and positive anti-thyroglobulin (Tg) antibody at 1 year post-initial treatment were significantly associated with the presence of CLT. Multivariate analysis revealed that patients with N1a stage (vs. N0 stage; hazard ratio [HR], 3.255; 95% confidence interval [CI], 1.290–8.213; p = 0.012) and positive anti-Tg antibody at 1 year post-initial treatment (vs. negative anti-Tg antibody; HR, 5.118; 95% CI, 2.130–12.296; p < 0.001) had poorer recurrence-free survival (RFS), while those with CLT (vs. no CLT; HR, 0.357; 95% CI, 0.157–0.812; p = 0.014) had favorable RFS outcomes.ConclusionsCLT is associated with less aggressive tumor characteristics and LN metastasis. Clinically LN-negative PTC patients with CLT experience longer RFS intervals than those without CLT.