Factor For Disease-free Survival Research Articles

Abstract PO5-04-10: Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status

Abstract Introduction: Metastatic Lymph Node Gene 51 Protein (MLN51) also known as Cancer Susceptibility Candidate Gene 3 Protein (CASC3) or Barentsz (BTZ) is a molecule that was first identified in malignant breast tumours. The CASC3 gene encodes the protein that binds to mRNA and is a key component of the exon junction complex (EJC), playing an important role in the metabolism of mRNA and in cellular recovery after stress responses. It is not clear, however, if MLN51 has a clinical value in assessing the disease progression of breast cancer. Methods: We analysed the transcription expression levels of MLN51 in a cohort of human breast cancer tissues and correlated the expression pattern with clinical outcome, pathological type and hormonal receptor status. Results: High levels of MLN51 was found to be a favourable prognostic indicator for overall survival (p=0.008, Hazard Ratio [HR=0.262]), the prognostic value being independent of other clinical and pathological factors. Likewise, high levels of MLN51 were also a significant and independent predictive factor for disease free survival (DFS) (p=0.003, HR=0.262). It was found that the favourable prediction in both OS and DFS was associated with node positive tumours, with significance with OS (p=0.004), compared in node negative tumours (p=0.143) and to DFS (p=0.001 in node positive compared with p=0.079 in node negative tumours). Levels of MLN51 had a significant correlation with EGFR in both normal and tumour mammary tissues but correlated with Her-2 and Her-3 in tumour tissues only. The prognostic power of MLN51 for DFS was significant in both Her-2 positive and Her-2 negative (p=0.003 and p=0.012) tumours and in ER negative tumours (p=0.003). The prediction for OS by MLN51 was particularly strong for Her-2 positive and ER positive (p=0.007 for both) tumours. Conclusions: MLN51 (CASC3) is a favourable prognostic factor in patients with breast cancer. This is clearly linked to the nodal status and hormone receptor status, particularly ER and HER-2. Citation Format: Binbin Cong, Tracey Martin, Xiaoshan Cao, Robert E Mansel, Eleri Davies, Wen Jiang. Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-10.

Abstract PO4-01-08: Co-expression of estrogen receptor (ER), progesterone receptor (PR), and Ki67 in a single breast cancer cell indicates a favorable prognosis in ER-positive breast cancer

Abstract Background: ER-positive breast cancer is biologically and clinically divided into two subtypes: luminal-A and luminal-B. This classification is mainly based on the status of cellular proliferation. At least two different pathways drive cellular proliferation in ER-positive breast cancer. One is a classical pathway where ER binds to estrogen responsive element (ERE), which leads to the expression of downstream molecules, including PR. The other is a non-classical pathway where a complex of ER and relevant factors bind to different sites than ERE. Growth factor signaling has been suggested to potentiate a non-classical pathway. We hypothesized that examining PR status in ER-positive proliferating cells could tell which pathway is more dominant in ER-positive breast cancer. Methods: To test the hypothesis, we used a newly developed triplex immunohistochemistry (IHC) that detects three molecules simultaneously under bright-field microscopy. Postmenopausal patients who were treated with neoadjuvant endocrine therapy with aromatase inhibitors from January 2007 to September 2016 at Saitama Cancer Center were included in this study. ER, PR, and Ki67 expressions were assessed in a single slide using the triplex IHC assay with anti-ER antibody (clone SP1), anti-PR antibody (clone 1E2), and anti-Ki67 antibody (clone 30-9). ER, PR and Ki67 expression was assessed in a single cell nucleus of cancer cells (567 to 4871 cells) from multiple areas in each case. An ER-positive proliferating cell was defined as an ER-positive and Ki67-positive cell. PR status in ER-positive proliferating cells was assessed. When PR was expressed in more than 50% of ER-positive proliferating cells in a clinical case, the tumor was categorized as the PR-positive group. Luminal A and luminal B breast cancers were defined based on the pre-treatment Ki67 labeling index with a cut-off of 14 %. Statistical analyses included the Mann-Whitney test, the log-rank test, and the Cox proportional hazard model. Results: Pre-treatment tissues from 55 patients were evaluated. The median age was 62 (range: 54 to 80) years. The patients were grouped into PR-positive and PR-negative groups. The two groups had no differences in age and pre-treatment T and N stages. The median pre-treatment Ki67 labeling index was 5.9 % in the PR-positive group and 9.9 % in the PR-negative group, which showed a statistically significant difference (P = 0.01). Clinical response to neoadjuvant endocrine therapy was compared, and no difference was observed. The median post-treatment Ki67 labeling index was 3.6 % in the PR-positive group and 13.1 % in the PR-negative group with a significant difference (P = 0.035). The survival was compared between the two groups. The PR-positive group showed a significantly more favorable disease-free survival (DFS) than the PR-negative group (P = 0.0079). To adjust for the background differences including Ki67 and PR status, a multivariate analysis was performed and showed that the PR-positive group had a significantly better DFS than the PR-negative group independent of clinical stage, Ki67 labeling index, and PR status (P = 0.042). Breast cancer-specific survival (BCSS) was also better in the PR-positive group than in the PR-negative group after adjusting for clinical stage, Ki67 labeling index, and PR status (P = 0.043). Interestingly, among patients with luminal A tumors, those in the PR-positive group showed a better DFS than those in the PR-negative group (P = 0.022). Conclusion: PR status in ER-positive proliferating cells was an independent prognostic factor in DFS and BCSS and divided patients with luminal A tumors further into two prognostic groups. Citation Format: Takayuki Ueno, Rie Horii, Hiroshi Matsumoto, Makiko Ono, Yurina Maeshima, Hiroaki Nitta. Co-expression of estrogen receptor (ER), progesterone receptor (PR), and Ki67 in a single breast cancer cell indicates a favorable prognosis in ER-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-08.

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation.

Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation invivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation invivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.

Impact of TP53-induced glycolysis and apoptosis regulator on malignant activity and resistance to ferroptosis in intrahepatic cholangiocarcinoma.

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

Transferrin Receptor is Associated with Sensitivity to Ferroptosis Inducers in Hepatocellular Carcinoma.

Transferrin receptor (TFR), a membrane protein that has a critical role in the transport of iron into cells, is known to be a ferroptosis-related marker. Although TFR is reported to be abundantly expressed in tumor cells, its relationship with ferroptosis inducers in hepatocellular carcinoma (HCC) remains unclear. The authors performed immunohistochemical staining of TFR and divided 350 HCC patients into two groups according to its expression. They analyzed the association between TFR expression and prognosis or clinicopathologic factors. In addition, the regulation of malignant activity and its effect on the efficacy of ferroptosis inducers were investigated in vitro. For this study, 350 patients were divided into TFR-positive (n =180, 51.4%) and TFR-negative (n = 170, 48.6%) groups. The TFR-positive group had more hepatitis B surface antigen (HBs-Ag) (p = 0.0230), higher α-fetoprotein (AFP) levels (p = 0.0023), higher des-gamma-carboxyprothrombin (DCP) levels (p = 0.0327), a larger tumor size (p = 0.0090), greater proportions of Barcelona Clinic Liver Cancer (BCLC) stage B or C (p = 0.0005), poor differentiation (p < 0.0001), and microscopic intrahepatic metastasis (p = 0.0066). In the multivariate analyses, TFR expression was an independent prognostic factor in disease-free survival (p = 0.0315). In vitro, TFRC knockdown decreased cell motility. In addition, TFRC knockdown abolished artesunate (AS)-, lenvatinib-, and sorafenib-induced ferroptosis in HCC cell lines. The study demonstrated that simultaneous treatment of AS with multi-kinase inhibitor augmented the ferroptosis-inducing effects of AS in HCC cell lines. TFR expression is a poor prognostic factor in HCC, but its expression increases sensitivity to ferroptosis-inducing agents.

Prediction of Surgical Outcome by Tumor Volume Doubling Time via Stereo Imaging Software in Early Non-Small Cell Lung Cancer.

Volume doubling time (VDT) has been proven to be a powerful predictor of lung cancer progression. In non-small cell lung cancer patients receiving sublobar resection, the discussion of correlation between VDT and surgery was absent. We proposed to investigate the surgical outcomes according to VDT. We retrospectively studied 96 cases post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating the VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days and VDT ≥ 133 days. Univariable and multivariable analyses were performed for comparative purposes. Univariable and multivariable analyses revealed that the consolidation and tumor diameter ratio was the factor of overall survival (OS), and VDT was the only factor of disease-free survival (DFS). The five year OS rates of patients with VDTs ≥ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9%, and the five year DFS rates were 95.9% and 61.5%. As VDT serves as a powerful prognostic predictor and provides an essential role in planning surgical procedures, the evaluation of VDT preoperatively is highly suggested.

Geriatric nutritional risk index as a prognostic marker for patients with upper tract urothelial carcinoma receiving radical nephroureterectomy

To investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with upper tract urothelial cell carcinoma (UTUC) receiving radical nephroureterectomy (RNU). Between January 2001 and December 2015, we enrolled 488 patients with UTUC underwent RNU in Taichung Veterans General Hospital. GNRI before radical surgery was calculated based on serum albumin level and body mass index. The malnutritional status was defined as GNRI < 92.0. Using Kaplan–Meier analyses and Cox proportional hazards models to analyze the risk factors on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). 386 patients were categorized as normal nutritional status (GNRI ≥ 92) and 102 patients as malnutritional status (GNRI < 92). We used the receiver operating characteristic (ROC) curve for determined the association between GNRI and OS, with area under the curve (AUC) being 0.69. The 5-year survival rate of DFS, CSS and OS were 48.6%, 80.5% and 80.5% in the normal nutritional group and 28.0%, 53.2% and 40% in the malnutritional group. Using the multivariate analysis, malnutritional status was found as an independent risk factor for OS (hazard ratio [HR] = 3.94, 95% confidence interval [CI] 2.70–5.74), together with age (HR = 1.04, 95% CI 1.02–1.06), surgical margin positive (HR = 1.78, 95% CI 1.13–2.82), pathological T3 (HR = 2.54, 95% CI 1.53–4.21), pathological T4 (HR = 6.75, 95% CI 3.17–14.37) and lymphovascular invasion (HR = 1.81, 95% CI 1.16–2.81). We also found GNRI index as independent risk factor in DFS (HR = 1.90, 95% CI 1.42–2.54) and CSS (HR = 5.42, 95% CI 3.24–9.06). Preoperative malnutritional status with low GNRI is an independent marker in predicting DFS, CSS and OS in UTUC patients underwent RNU.

Comparing clinical characteristics and surgical outcomes of gastric and small bowel GIST: A single center experiences

ObjectiveGastrointestinal stromal tumor (GIST) is a rare kind of neoplasm at the gastrointestinal tract. There are few studies regarding the comparison of gastric and small bowel GIST in Korea. We aimed to analyze clinical characteristics and outcomes between gastric and small bowel GIST after curative resection. MethodsBetween May 2005 and Dec 2017, 165 patients who underwent curative resection for gastric GIST (n = 115) and small bowel GIST (n = 50) were retrieved from a retrospective database. They were compared with respect to clinical, pathologic and oncological outcomes. ResultsThe mean age at surgery in both two group was similar (58.8 vs. 58.6, p = 0.772). The rate of emergency admission and surgery was higher in small bowel GIST group (p < 0.005). The mitotic rate and risk category were not significantly different between the two groups. However, the T stage was higher in small bowel GIST compared to the T stage of gastric GIST (22.6% vs. 44.0%, p = 0.025). During the follow-up, 5-year disease free survival rate was worse in small bowel GIST (82.0%) compared gastric GIST (93.7%) (p = 0.032). 5-year survival rate was not significantly different between the two groups (100.0% vs. 97.7%, p = 0.578). The T stage, mitotic count, and risk category were independent prognostic factors for disease free survival of Gastric and small bowel GIST in Cox multivariate analysis. ConclusionSmall bowel GIST has more advanced T stage and higher rate of emergency surgery. Disease free survival rate was worse in small bowel GIST. Larger scaled prospective study of small bowel GIST is needed.

Combined Inflammation and Nutrition Factors Reinforce the Prognostic Prediction for Stage III Colorectal Cancer Patients.

Previous studies have shown that postoperative adjuvant chemotherapy improves overall survival in patients with stage III colorectal cancer (CRC). However, adjuvant chemotherapy may not be necessary for some patients. This study aimed to develop a new nutritional-inflammation score, which would be useful in identifying a favorable prognosis group among stage III CRC patients. This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and a new prognostic model was developed. Multivariate analyses in TS revealed that lymph node metastasis (N2) (p=0.002), low albumin (p=0.017), high monocyte counts (p=0.008), and low platelet counts (p=0.018) were independent risk factors for disease free survival (DFS). The Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dl albumin level, >450 monocyte counts, and <1.65×105 platelet counts. Using KPS, DFS and overall survival (OS) were validated in VS. The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. KPS serves as a new model for the prognosis of patients with stage III CRC.

Platin‑based chemotherapy does not improve survival in patients with non‑metastatic resected typical carcinoid tumors.

Chemotherapy is controversial in non-metastatic typical carcinoid (TC) tumors. Therefore, it was aimed to evaluate the impact of platin-based chemotherapy on the survival of patients with lung TC. The medical records of patients who underwent surgical resection for non-metastatic TC from 2002 to 2020 at our institution were retrospectively reviewed. Multivariate regression analysis was performed for chemotherapy and prognostic factors in disease-free survival (DFS) in 72 patients. The pathological stages of patients were as follows: 73.6% of the patients were in stage I, 15.3% in stage II and 11.1% in stage III. A total of 5 patients (6.9%) received platin-based chemotherapy and 6 patients (8.3%) had recurrences. The DFS rates at 12, 36 and 60 months were 98.5, 95.1 and 92.5%, respectively. Log-rank testing showed that patients who received chemotherapy and had stage III disease had shorter DFS (P=0.021 for chemotherapy and P<0.001 for stage). However, multivariate analysis revealed that the pathological stage was the only statistically significant factor affecting DFS (P=0.016). Platin-based chemotherapy did not improve DFS, and the eighth edition of TNM (tumor, nodes, metastases) staging did have prognostic value for patients with non-metastatic TC. Although resection has satisfying long-term outcomes, studies on new agents are needed to decrease the recurrence rate, particularly in patients with stage III disease.

Identifying prognostic parameters related to surgical technique in patients treated by robotic radical prostatectomy

Introduction and objectiveThe most frequently studied factors in patients treated by robotic radical prostatectomy are PSA and pathological features of the biopsy and prostatectomy specimen. Studies on the factors associated with the surgical technique are scarce and with controversial results. The objective is to identify all possible surgical factors and their relationship with disease-free and metastasis-free survival. Patients and MethodProspective study approved by the Ethics Committee, including patients who underwent robotic radical prostatectomy since January 2009 with a minimum follow-up of 5 years. Surgeon, surgical time, blood loss, fascial access, continence techniques, preservation of the fascia, neurovascular bundles, bladder neck, urethra, learning curve and surgical complications, were analyzed as possible prognostic factors. We performed univariate and matched comparisons of survival using Kaplan–Meier estimation and long-rank tests. The significance level for multiple comparisons was established with False Discovery Rate-adjustment (adjusted p). ResultsCohort of 667 patients with a median follow-up of 69 months. In univariate analysis, surgeon (adjp=0.018), preservation of puboprostatic ligaments (adjp=0.02), preservation of endopelvic fascia (adjp=0.001) and performing periurethral suspension (adjp<0.001) are poor prognostic factors for disease-free survival. Fascia preservation also negatively affects metastasis-free survival (adjp=0.04). Previous abdominal surgeries, prostate, surgical time, blood loss, type of residual urethra, middle lobe, fascial access, fascia or bladder neck preservation, have no statistical significance. ConclusionsThe surgeon and specific aspects of the surgical technique are determining factors in disease-free survival. Preservation of the fascia is the only factor that negatively affects metastasis-free survival.

Prognostic significance of 4R lymph node dissection in patients with right primary non-small cell lung cancer

BackgroundTo investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC).MethodsWe performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection.ResultsOur study included 2070 patients, with 207 patients having no station 4R dissection (S4RD− group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD− group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08–1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04–1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002).ConclusionsStation 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.

Identificación de parámetros pronósticos relativos a la técnica quirúrgica en pacientes tratados mediante prostatectomía radical robótica

Introduction and objectiveThe most frequently studied factors in patients treated by robotic radical prostatectomy are PSA and pathological features of the biopsy and prostatectomy specimen.Studies on the factors associated with the surgical technique are scarce and with controversial results. The objective is to identify all possible surgical factors and their relationship with disease-free and metastasis-free survival. Patients and MethodProspective study approved by the Ethics Committee, including patients who underwent robotic radical prostatectomy since January 2009 with a minimum follow-up of 5 years.Surgeon, surgical time, blood loss, fascial access, continence techniques, preservation of the fascia, neurovascular bundles, bladder neck, urethra, learning curve and surgical complications, were analyzed as possible prognostic factors.We performed univariate and matched comparisons of survival using Kaplan-Meier estimation and long-rank tests. The significance level for multiple comparisons was established with False Discovery Rate-adjustment (adjusted p). ResultsCohort of 667 patients with a median follow-up of 69 months.In univariate analysis, surgeon (adjp = 0.018), preservation of puboprostatic ligaments (adjp = 0.02), preservation of endopelvic fascia (adjp = 0.001) and performing periurethral suspension (adjp < 0.001) are poor prognostic factors for disease-free survival. Fascia preservation also negatively affects metastasis-free survival (adjp = 0.04).Previous abdominal surgeries, prostate, surgical time, blood loss, type of residual urethra, middle lobe, fascial access, fascia or bladder neck preservation, have no statistical significance. ConclusionsThe surgeon and specific aspects of the surgical technique are determining factors in disease-free survival. Preservation of the fascia is the only factor that negatively affects metastasis-free survival.

Correlation between Characteristics of Lymph Node Metastasis and Prognosis of N1-N2 Stage Non-small Cell Lung Cancer

Objective: Patients with non-small cell lung cancer have prognostic heterogeneity, chief prognosis factor of them lymph node metastasis. Our study aimed to evaluate the correlation between lymph node ratio, the number of involved lymph node stations and skip-N2 metastasis and prognosis of N1-N2 stage non-small cell lung cancer. Methods: A total of 374 patients with N1 and N2 stage non-small cell lung cancer were retrospectively analyzed who underwent radical resection at the Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University from January 2012 to December 2019. Cox regression was conducted to identify the independent prognosis factors for N1-N2 stage non-small cell lung cancer. Survival curves were plotted by Kaplan-Meier method. Subgroup analyses were performed regarding proposals for the revision of the N descriptors in the 8th edition of the TNM classification. Results: Multivariate analysis of Cox regression model confirmed that smoking history, multiple-station lymph node metastasis and lymph node rate were independent prognosis factors for disease-free survival. Male, smoking history, multiple-station lymph node metastasis, lymph node ratio, adjuvant chemotherapy and targeted therapy were independent prognosis factors for overall survival. The 5-year overall survival was 57.4% in skip N2 group, while being 65.1% in N1 group (P=0.138) and 36.2% in the non-skip N2 group (P=0.007). Conclusion: Combined with lymph node ratio, the number of involved lymph node stations and skip metastasis, we can effectively predict the inter-subgroup survival difference.

The Impact of Minimally Invasive Surgery on Treating Patients with Early Cervical Adenocarcinoma

Objective To explore the impact of minimally invasive surgery on treating patients with early cervical adenocarcinoma (CA). Methods From April 2016 to December 2019, patients with early CA and underwent surgery were prospectively included in this study. They were randomly divided into 2 groups: the minimally invasive surgery (MIS) group and conventional laparotomy (CL) group. The baseline characteristics, pathological features, surgical related parameters, serum tumor markers, complications and prognosis were analyzed and compared between the 2 groups. The risk factors for disease free survival (DFS) and overall survival (OS) were also analyzed with logistic regression analyses. Result The baseline characteristic and pathological features had no statistical difference between the 2 groups. The mean operation duration in MIS group was significantly longer than CL group (262.39 ± 34.98 vs 241.29 ± 36.98 min, P < 0.001). The intraoperative blood loss volume (189.87 ± 23.87 vs 306.87 ± 24.98 mL, P < 0.001), postoperative anal exhaust time (45.98 ± 4.39 vs 59.87 ± 4.87 days, P < 0.001), catheter removal time (18.29 ± 3.21 vs 21.53 ± 3.19 days, P < 0.001) and length of hospital stay (12.98 ± 2.09 vs 16.98 ± 2.32 days, P < 0.001) were significant lower in MIS group. The serum tumor markers decreased significantly postoperative in both groups with no different levels between the 2 groups. The incidence of complications had no difference between the 2 groups except lymphocysts (P = 0.023). After mean follow up time for 4.23 ± 0.34 years, the DFS rate and OS rate also had no statistical difference between the 2 groups (P = 0.069 and 0.151, respectively). Conclusion Extensive hysterectomy with MIS was equally efficacy and safe to CL.

Recurrence dynamics after curative surgery in patients with invasive mucinous adenocarcinoma of the lung

BackgroundWe investigated the patterns and timing of recurrence and death as well as prognostic factors based on clinicopathological and radiological factors in patients who underwent surgical treatment for invasive mucinous adenocarcinoma (IMA).MethodsWe reviewed clinicopathological findings including spread through air spaces (STAS) and CT findings of IMA such as morphology, solidity, margin, well-defined heterogeneous ground-glass opacity, CT angiogram, and air bronchogram signs from 121 consecutive patients who underwent surgical resection. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified. Hazard rate analyses were performed for the survival dynamics.ResultsT stage (hazard ratio [HR] = 4.102, p = 0.03), N stage (N2 vs. N0, HR = 7.653, p < 0.001), and consolidative CT morphology (HR = 3.556, p = 0.008) remained independent predictors for DFS. Age (HR = 1.110, p = 0.002), smoking (HR = 12.893, p < 0.001), T stage (HR = 13.005, p = 0.006), N stage (N2 vs. N0, HR = 7.653, p = 0.004), STAS (HR = 7.463, p = 0.008), and consolidative CT morphology (HR = 6.779, p = 0.007) remained independent predictors for OS. Consolidative morphology, higher T and N stage, and presence of STAS revealed initial sharp peaks after steep decline of the hazard rate curves for recurrence or death in follow-up period.ConclusionsConsolidative morphology, higher T and N stage, smoking, and STAS were indicators of significantly greater risk of early recurrence or death in patients with IMA. Thus, these findings could be incorporated into future surveillance strategies.

Non-phosphorylated Tyr-1248 form of human epidermal growth factor receptor 2 (HER2) predicts resistance to trastuzumab therapy and poor disease-free survival of HER2-positive breast cancer patients

AimTo determine the predictive value of phosphorylated human epidermal growth factor receptor 2 (pHER2Y1248) status in breast cancer (BC) patients undergoing trastuzumab-based adjuvant therapy.MethodsImmunohistochemical status of pHER2Y1248, EGFR/HER1, HER3, and HER4 was determined in 124 consecutive HER2-positive BC patients (median age [range] = 57 years [49.0-64.0]) treated at the University Hospital for Tumors, Zagreb, between 2008 and 2011. The median follow-up was 84 months (60.0-84.0). Prognostic factors of disease free survival (DFS) rate were evaluated with Kaplan-Meier/log-rank test and Cox regression analysis.ResultspHER2Y1248, HER1, HER3, and HER4 were expressed in 66.1%, 9.7%, 70.2%, and 71.0% of patients, respectively. Disease progression (DP) was observed in 17.1% of pHER2Y1248-positive and 47.6% of pHER2Y1248-negative BCs (P = 0.001). Kaplan-Meier analysis showed a worse five-year DFS in pHER2Y1248-negative patients who were older than 60 years (P < 0.001) and had positive lymph node status (P < 0.001); tumor size >2.0 cm (P < 0.001); higher histological grade (P < 0.001); HER2E intrinsic subtype (P < 0.001), negative hormone receptors (P < 0.001); negative HER1 status (P < 0.001), positive HER3 (P = 0.002); and/or positive HER4 (P = 0.002) status. The only negative prognostic factor for five-year DFS in multivariate Cox regression analysis was pHER2Y1248-negative (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.8-7.2, P < 0.001) and lymph node-positive status (HR 3.6, 95% CI 1.3-9.8, P = 0.014).ConclusionpHER2Y1248 predicts sensitivity to trastuzumab and a better five-year DFS regardless of any other prognostic parameter. In HER2-positive BC patients. Non-phosphorylated HER2Y1248 is a strong predictor of trastuzumab resistance and a poor DFS.

Skeletal muscle loss during neoadjuvant chemotherapy predicts poor prognosis in patients with breast cancer

BackgroundThe skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level divided by height squared, has been considered a prognostic factor in patients with breast cancer. However, the prognostic impact of changes in SMI during treatment remains unclear. This study aimed to evaluate the influence of SMI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).MethodsWe reviewed patients with breast cancer who underwent NAC and subsequent surgery for breast cancer between 2010 and 2017. The rate of SMI change during NAC was calculated, and the association between SMI changes and prognosis was retrospectively analyzed.ResultsIn total, 141 patients were evaluated. 48 (34.0%), 53 (37.6%), and 40 (28.4%) patients exhibited increased (≥ 3%), maintained (− 3% <, < 3%), and decreased (− 3% ≥) SMI during NAC, respectively. The decreased SMI group showed significantly poorer disease-free survival than the maintained and increased SMI groups (hazard ratio [HR] 8.29, p < 0.001 for the decreased vs. increased SMI groups; HR 3.49, p < 0.001 for the decreased vs. maintained SMI groups). Moreover, decreased SMI was an independent risk factor for disease-free survival in multivariate analysis (HR 3.68, p < 0.01).ConclusionsSkeletal muscle loss during NAC predicts poor prognosis. Our results underscore the importance of monitoring and maintaining skeletal muscle mass during NAC.

Ground Glass Opacity and Adjuvant Chemotherapy in Pathological Stage IB-IIA Lung Adenocarcinoma.

BackgroundThe prognostic value of ground glass opacity (GGO) in stage IA non-small cell lung cancer (NSCLC) has been widely recognized. However, studies investigating its value in the related stage IB–IIA lung adenocarcinoma (LUAD) remains lacking. The impact of adjuvant chemotherapy (ACT) on pathological stage IB–IIA LUAD is also controversial.Materials and MethodsWe retrospectively reviewed the clinical records of 501 patients with pathological stage IB–IIA LUAD at the Sun Yat-sen University Cancer Center from January 2008 to June 2018. We calculated and compared survival curves using the Kaplan–Meier test and log-rank test. Cox regression models were performed to determine independent prognostic factors of disease-free survival (DFS) and overall survival (OS). We established nomograms to predict the OS and DFS of LUAD patients. Calibration and receiver operator characteristic curves were conducted to assess the predictive performance of two nomograms. Based on the nomogram, we identified candidate patients that may most benefit from ACT after surgery.ResultsThe number of patients with pure solid, part GGO, and pure GGO nodules was 240, 242, and 19, respectively, and 125 patients who received ACT. Patients with consolidation-to-tumor ratio (CTR) <0.75 had longer OS (P = 0.026) and DFS (P = 0.003). Pathological tumor size and at least 10 lymph nodes (LNs) resection were independent prognostic factors of both OS and DFS. CTR <0.75 was positively associated with DFS. The C-index of nomograms predicting individual OS and DFS was 0.660 and 0.634, respectively. Based on the nomogram for OS, ACT was found to be a positive prognostic indicator of OS (P = 0.031, HR = 0.5141, 95% CI 0.281–0.942) in patients with nomogram total points ≥5.ConclusionCTR <0.75 is associated with a better DFS in patients with stage IB–IIA LUAD. Nomograms developed by integrating pathological tumor size, at least 10 LNs resection, and CTR ≥0.75 for predicting individual OS and DFS displayed a good predictive capacity and clinical value, which were also proved to be a useful tool for selecting patients most benefiting from ACT.

Clinical Implications of Age in Differentiated Thyroid Cancer: Comparison of Clinical Outcomes between Children and Young Adults.

Background Pediatric patients with differentiated thyroid cancer (DTC) present with unique characteristics compared to adult patients. This study aimed to evaluate clinical presentation and surgical outcomes according to age and to identify the clinical significance of age in DTC. Methods In total, 98 pediatric patients, 1261 young adult patients, and 4017 adult patients with DTC who underwent thyroid surgery between January 1982 and December 2012 at Yonsei University Hospital (Seoul, Republic of Korea) were retrospectively reviewed. The mean follow-up duration was 120.4 ± 54.2 months. Results Mean tumor size was significantly larger in the pediatric group than in the adult groups (p < 0.001). The recurrence rate was significantly higher in the pediatric group (14.3% versus 6.6% versus 3.0%, p=0.004 and p < 0.001). In multivariate analysis, the risk of disease-free survival (DFS) was lower in the adult group (HR, 0.362; p < 0.001). Reanalysis of patients with tumor size of 2–4 cm revealed that the adult group was not a significant risk factor for DFS in multivariate analysis (HR, 0.305; 95% CI, 0.158 to 0.588; p < 0.001). Conclusions Our findings suggest that pediatric patients present with more aggressive features and higher recurrence rates compared to adult patients and should be carefully treated from initial evaluation to surgery and postoperative care.