Prognostic Factor For Disease-free Survival Research Articles

Tumor-Infiltrating Lymphocytes as Biomarkers of Treatment Response and Long-Term Survival in Patients with Rectal Cancer: A Systematic Review and Meta-Analysis.

Simple SummaryThis study investigated tumor-infiltrating lymphocytes (TILs) in pretherapeutic biopsies as biomarkers of treatment response and long-term prognosis in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. The results indicate that it is possible to identify a sub-group of patients with improved treatment response and long-term prognosis by assessing the density of CD8+ TILs at the time of diagnosis.Neoadjuvant chemoradiotherapy (NCRT) is indicated in locally advanced rectal cancer (LARC) to downstage tumors before surgery. Watchful waiting may be a treatment option to avoid surgery in patients, obtaining a complete clinical response. However, biomarkers predictive of treatment response and long-term prognosis are lacking. Here we investigated tumor-infiltrating lymphocytes (TILs) in pretherapeutic biopsies as predictive and prognostic biomarkers. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. In total, 429 articles were identified, of which 19 studies were included in the systematic review and 14 studies in the meta-analysis. Patients with high pretherapeutic CD8+ TILs density had an increased likelihood of achieving a pathological complete response (RR = 2.71; 95% CI: 1.58–4.66) or a complete or near-complete pathological treatment response (RR = 1.86; 95% CI: 1.50–2.29). Furthermore, high CD8+ TILs density was a favorable prognostic factor for disease-free survival (HR = 0.57; 95% CI: 0.38–0.86) and overall survival (HR = 0.43; 95% CI: 0.27–0.69). CD3+, CD4+, and FOXP3+ TILs were not identified as predictive or prognostic biomarkers. Thus, assessing pretherapeutic CD8+ TILs density may assist in identifying patients with increased sensitivity to NCRT and favorable long-term prognosis.

The Prognostic Role of m6A-Related Genes in Paediatric Neuroblastoma Patients.

Methods The gene expression data were extracted from the “Therapeutically Applicable Research to Generate Effective Treatments” (TARGET) database. The differentially expressed genes (DEGs) were identified, and the relationships between DEGs and m6A genes were explored. Then, the correlations among the m6A genes in neuroblastoma were investigated. Finally, the prognostic role of the m6A genes was studied, and the risk model was constructed. Results 81 NB patients were extracted from the TARGET database. After comparing the gene expression between unfavorable and favorable outcome groups, 73 DEGs were identified, including 54 downregulated genes and 19 upregulated genes. In NB patients, we found that IGF2BP3, METTL14, and METTL16 are prognostic factors for disease-free survival (DFS) while IGF2BP3, METTL14, and METTL16 are prognostic factors for overall survival (OS). Besides, after the risk model construction, the OS between the two risk groups was drawn (log-rank p = 1.64e − 08, HR = 3.438, 95% CI 2.24-5.278). The 1-, 3-, and 5-year time-dependent receiving operating characteristic (ROC) curves were also illustrated, and the areas under the receiver operating characteristic curves (AUCs) attained 0.75, 0.798, and 0.768, respectively. Conclusions IGF2BP3, METTL14, and METTL16 were identified as the significant factors for DFS and OS in NB patients.

Clinical Significance of Surgical Resection Timing from Endoscopic Stenting for Left-Sided Large-Bowel Obstruction in Colorectal Cancer.

The optimal interval between self-expanding metallic stent (SEMS) insertion and surgery remains controversial in malignant left-sided large-bowel obstruction (MLLO), especially with respect to oncologic aspects. The aim of this study is to examine whether the time interval to surgery is related to oncologic outcomes. Prospectively collected database of MLLO between January 2005 and December 2017 were reviewed. They were divided according to established cut-off value of 14days for the time interval to surgery. The two groups (early and late groups) were compared with respect to disease-free survival (DFS) and overall survival (OS). Additional subgroup analysis was performed using the established cut-off values for patients with stage II and III tumors. A total of 149 patients underwent surgery after SEMS insertion. There were no significant differences between the early and late groups in the 5-year DFS (78.0% vs 72.4%; P = 0.513) and the OS (74.2% vs 75.7%; P = 0.864) rates in all MLLO. Subgroup analysis showed that there were significant differences between the two groups for DFS and OS in stage II MLLO. The multivariate Cox regression analysis in stage II MLLO demonstrated that the time to surgery was a prognostic factor for DFS (HR, 2.051; 95% CI, 1.528-42.136; P = 0.014) and for OS (HR, 4.947; 95% CI, 1.520-16.107; P = 0.008). The time to surgery was demonstrated not to be a significant prognostic factor in all MLLO. However, it was a prognostic factor for patients with stage II MLLO.

Clinical Implication of KRAS Mutation Variants in Patients With Resected Colon Cancer.

This study evaluated the clinical implication of KRAS proto-oncogene, GTPase (KRAS) mutation variants in patients with resected colon cancer (CC). We retrospectively reviewed 482 patients diagnosed with CC who underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The inclusion criteria were: Pathologically diagnosed with primary CC; stage I-III CC according to the 7th edition of American Joint Committee on Cancer staging system; and with available test results for KRAS mutation status. In total, 345 patients met these criteria and were included in this study. Among the 345 patients, 140 (40.6%) exhibited KRAS mutations, with their incidences as follows: 90/140 (64.3%) in exon 2 codon 12, 37/140 (26.4%) in exon 2 codon 13, 1/140 (0.1%) in exon 3 codon 59, 7/140 (5.0%) in exon 3 codon 61, and 5/140 (3.6%) in exon 4 codon 146. KRAS mutation status was not a significant prognostic factor for disease-free survival or overall survival. Although there were no significant differences in survival between patients with exon 2 codon 12 and exon 2 codon 13 mutations, poorer disease-free survival (p=0.085) and overall survival (p=0.005) were seen in those with exon 3 codon 61 mutation than in others. KRAS mutation status was not correlated with survival, but exon 3 codon 61 mutation might be a factor for poor prognosis in patients after resection of CC.

Tumor Volume Reduction Rate to Induction Chemotherapy is a Prognostic Factor for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Retrospective Cohort Study.

Introduction: Aim of this retrospective cohort study is to evaluate the prognostic value of tumor volume reduction rate status post-induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Methods: Patients newly diagnosed from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received induction Taxotere, Platinum, Fluorouracil followed by daily definitive intensity-modulated radiotherapy for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate was measured and calculated by contrast-enhanced computed tomography images at diagnosis, and after at least 1 cycle of induction chemotherapy, and analyzed though a univariate and multivariate Cox regression model. Results: Ninety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%), and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In multivariate Cox regression analysis, the tumor volume reduction rate of the primary tumor (TVRR-T) was also an independently significant prognostic factor for disease-free survival (DFS) (hazard ratio 0.77, 95% confidence interval 0.62-0.97; P-value = .02). Other factors including patient's age at diagnosis, the primary cancer site, and RECIST (Response Evaluation Criteria in Solid Tumors), were not significantly related. At a cutoff value using 50% in Kaplan–Meier survival analysis, the DFS was higher with TVRR-T ≥ 50% group (log-rank test, P = .024), and a trend of improved overall survival. (log-rank test, P = .069). Conclusion: TVRR-T is a probable prognostic factor for DFS. With a cut-off point of 50%, TVRR-T may indicate better DFS.

Icotinib Enhanced Radiosensitization of Nasopharyngeal Carcinoma by Inhibiting the Expression of Epidermal Growth Factor Receptor

Epidermal growth factor receptor (EGFR) is frequently overexpressed in multiple malignancies. Icotinib (IH), a new EGFR tyrosine kinase inhibitor, enhances radiosensitivity in various types of cancer, but its effect on nasopharyngeal carcinoma (NPC) remains unclear. Total 115 NPC tissue sections and 30 nasopharyngitis tissue sections were enrolled. The correlation of EGFR expression and clinicopathologic features of NPC was analyzed. Survival analysis was calculated by using univariate and multivariate regression analysis. A radioresistant NPC cell line, CNE-2R, was established with a gradient irradiation schedule. Cell viability, colony formation and EGFR expression of CNE-2/2R cells were examined. Significant higher expression of EGFR was observed in NPC tissues than chronic nasopharyngitis lesions. EGFR expression was significantly correlated with both tumor stage (P < 0.001) and tumor-node-metastasis stage of NPC (P = 0.006). EGFR expression was an independent prognostic factor of disease-free survival (P = 0.047) and the overall survival of NPC (P = 0.016). Cell viability was higher in CNE-2R than CNE-2 on days 1, 2, 4, and 6 after radiation of 4 Gy. The colony number of CNE-2R was significantly higher than that of CNE-2 (P < 0.05), while IH enhanced the radiosensitizing effect of CNE-2R with lower survival fraction (P < 0.05). EGFR mRNA and protein expression levels were significantly higher in CNE-2R cells compared to CNE-2 cells, but significantly decreased after IH treatment (all P < 0.05). In conclusion, high EGFR expression is a poor prognostic factor for NPC patients. IH enhances the radiosensitivity of CNE-2R cells and reduce EGFR expression.

Determining Prognostic Factors of Disease-Free Survival in Breast Cancer Using Censored Quantile Regression.

Background:The analysis of disease-free survival and related factors leads to a better understanding of the patient’s condition and recurrence-related characteristics and provides a basis for more appropriate treatment guidance. In this study, we aimed to investigate the role of prognostic factors on disease-free survival in breast cancer with a quantile regression model.Methods:This retrospective study was conducted by reviewing data obtained from 2056 breast cancer patients. Age at diagnosis and education status, tumor size, lymph node ratio, tumor grade, estrogen receptor and progesterone receptor, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were the prognosis factors considered in this study. A quantile regression model was used to investigate prognostic factors of disease-free survival in breast cancer.Results:Disease recurrence was verified in 251 (13.9%) women, and 39 (0.02%) women died before experience recurrence. The 10th percentile of disease-free survival for patients with the hormone therapy was 23.85 months greater than patients who did not receive this treatment (P value < .001). In the examination of the tumor size, the 10th and 20th percentiles of disease-free survival for patients with tumor size > 5 cm were 31.06 and 27 months less than patients with the tumor size < 2 cm, respectively (P value = .006 and .021, respectively). Compared with grade 1 tumors, the 10th and 20th percentiles of disease-free survival for patients with grade 3 tumors decreased 30.11 and 38.32 months, respectively (P value < .001 and .038, respectively). The 10th and 20th percentiles of disease-free survival decreased 28.16 and 45.32 months with a 1 unit increase in lymph node ratio, respectively (P value = .032 and .032, respectively).Conclusions:Among the prognostic factors, tumor size, grade, and lymph node ratio showed a close relationship with disease-free survival in breast cancer. The findings indicated that developing public screening and educational programs through the health care system with more emphasis on low-educated women is needed among Iranian women.

Prognostic value of pretreatment systemic inflammatory markers in patients with stage I endometrial cancer

Objective: Evaluate the prognostic value of monocyte-lymphocyte ratio (MLR) in patients with stage I endometrial cancer. Method: Data from 225 patients with stage I endometrioid endometrial cancer who underwent surgical resection between January 2010 and December 2020 were reviewed. The receiver operating characteristic (ROC) curves were generated for the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and MLR. Optimal cut-off values were determined as the points at which the Youden index (sensitivity + specificity - 1) was maximal. Based on the results of the ROC curve analysis, the patients were grouped into high MLR and low MLR groups. Recurrence rate, and disease-free survival were compared between the two groups. The prognostic factors were investigated using univariate and multivariate Cox proportional hazards model. Results: The optimal cut-off value of MLR was 0.220 (AUC, 0.835; p < 0.001). Significantly more patients in the high MLR group experienced recurrence (20.3% vs. 1.9%, p < 0.0001). In multivariate analysis, grade, depth of myometrial invasion, adjuvant RT, and high MLR were independent prognostic factors for disease-free survival. Conclusion: Elevated MLR was significantly associated poor clinical outcomes in patients with stage I endometrioid endometrial cancer. Our findings suggest that MLR may be clinically reliable and useful as an independent prognostic marker for patients with stage I endometrioid endometrial cancer.

Prognostic factors in mammary analogue secretory carcinomas of the parotid gland: Systematic review and meta-analysis.

Mammary analogue secretory carcinomas (MASCs) of the parotid gland are considered as low-grade malignancies with good clinical outcome but lacking data regarding prognostic factors. We performed meta-analysis assessing prognostic factors for disease-free survival (DFS) and overall survival (OS) in 256 patients with MASCs of the parotid gland. A total of 73 studies have met the inclusion criteria and 76.3% of patients were seen with T1 and T2 tumors and negative neck nodes. Lymph node metastasis (57.4%) and distant recurrences (46.2%) were particularly found in T4 tumors (p < 0.001). DFS at 5 and 10 years was 77.9% and 47.2% compared to 88.1% and 77.2% for OS at the same time points. Male sex, T3-T4 tumors, and recurrent disease represented independent worse prognosticators for survival outcome. Altogether, parotid gland MASCs show good long-term outcome, but T4 tumors behave significantly more aggressive and require extended treatment strategies along with close follow-ups.

Survival after cytoreductive surgery for peritoneal metastases in colorectal cancer patients: Does a history of resected liver metastases worsen the prognosis?

BackgroundNowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown. AimThe aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR). MethodsAnalysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020. ResultsAll patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found. ConclusionsLR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.

TRIM39 is a poor prognostic factor for patients with estrogen receptor-positive breast cancer and promotes cell cycle progression.

Tripartite motif (TRIM) family proteins are involved in various biological processes and the pathophysiology of cancers. However, the roles of TRIM39, a TRIM family member, in breast cancer is not well-understood. Here, we performed immunohistochemical study of TRIM39 protein in clinical estrogen receptor-positive (ER+ ) breast cancer tissues from 108 patients. TRIM39 immunoreactivity (IR) was positively correlated with advanced stage (p < 0.001), large invasive tumor size (p = 0.012), and positive lymph node status (p = 0.002). Positive TRIM39 IR was significantly correlated with short disease-free survival (DFS) (p = 0.001). Multivariate analysis revealed that the TRIM39 status is an independent prognostic factor in DFS (p = 0.049). Microarray analysis of MCF-7 breast cancer cells treated with siRNA revealed that TRIM39 knockdown downregulated the cell cycle- and cell division-related genes, including MLLT11, CDCA3, CDC25C, BIRC5, and ANP32E. Consistently, TRIM39 knockdown significantly suppressed proliferation and cell cycle transition to S phase in MCF-7 and 4-hydroxytamoxifen-resistant (OHTR) breast cancer cells. These results suggest that TRIM39 promotes ER+ breast cancer growth by promoting cell cycle progression.

The Prognostic Role of Blood Inflammatory Biomarkers and EGFR Mutation Status in Stage IIIA/N2 Non-Small Cell Lung Cancer Patients Treated With Trimodality Therapy.

ObjectivesVarious blood inflammatory biomarkers were associated with treatment response and prognosis of non-small cell lung cancer (NSCLC) in previous studies. In this study, we retrospectively evaluated the prognostic role of pretreatment blood inflammatory biomarkers and epidermal growth factor receptor (EGFR) mutation status in stage IIIA/N2 NSCLC patients with trimodality therapy.MethodsCompletely resected stage IIIA/N2 NSCLC patients with adjuvant chemotherapy and postoperative radiotherapy (PORT) were assessed in this study. Cutoff values of blood inflammatory factors were calculated by the R package SurvivalROC of R software. SPSS Statistics software was used for survival analyses. Kaplan-Meier survival curve and log-rank test were used to compare the survival difference between every two groups. Univariate and multivariate analyses of predictive factors were performed by Cox proportional hazards regression model.ResultsThe univariate analysis showed that T stage (p=0.007), EGFR mutation status (p=0.043), lymphocyte-to-monocyte ratio (LMR) (p=0.067), and systemic immune-inflammation index (SII) (p=0.043) were significant prognostic factors of disease-free survival (DFS). In the multivariate analysis, T2 (HR=0. 885, 95% CI: 0.059-0.583, p=0.004), EGFR mutation-positive (HR=0.108, 95% CI: 0.023-0.498, p=0.004) and elevated pretreatment SII (HR=0.181, 95%CI: 0.046-0.709, p=0.014) were independently related to shorter DFS. High pretreatment neutrophil counts (HR=0.113, p=0.019) and high systemic inflammation response index (SIRI) (HR=0.123, p=0.025) were correlated with worse overall survival (OS) by the univariate analysis. In the multivariate analysis, only high pretreatment SIRI was an independent predictor for poorer OS (HR=0.025, 95% CI: 0.001-0.467, p=0.014).ConclusionsIn conclusion, we identified that high pretreatment SII and SIRI were unfavorable prognostic factors in stage IIIA/N2 NSCLC patients treated with surgery, adjuvant chemotherapy and PORT. Patients with high pretreatment SII, high pretreatment SIRI, T2, and EGFR mutation-positive may need more forceful adjuvant treatment. Further prospective studies with large-scale are needed to validate our results and identify the proper cut-off values and optimum adjuvant treatment for distinct patient population.

Impact of cumulative cisplatin dose in childhood nasopharyngeal carcinoma based on neoadjuvant chemotherapy response in the intensity-modulated radiotherapy era: a real-world study

BackgroundWe aimed to comprehensively investigate the optimal cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) for locoregionally advanced nasopharyngeal carcinoma (CA-LANPC) with different tumor responses after neoadjuvant chemotherapy (NAC).MethodsPatients with CA-LANPC who underwent NAC followed by cisplatin-based concurrent chemoradiotherapy were retrospectively analyzed. Evaluation of tumor response in patients was conducted by Response Evaluation Criteria for Solid Tumor (RECIST) 1.1 after two to four cycles NAC. Multivariate Cox proportional hazards models were used for prognosis. Recursive partitioning analysis (RPA) was conducted to classify participates and predict disease-free survival (DFS).ResultsOne hundred and thirty-two patients with favorable response after NAC were included. The median CC-CCD was 163 mg/m2 (IQR, 145–194 mg/m2), and 160 mg/m2 was selected as the cutoff point to group patients into low and high CC-CCD groups (< 160 vs. ≥ 160 mg/m2). There was significant improvement in 5-year DFS (91.2% vs. 72.6%; P = 0.003) for patients receiving high CC-CCD compared to those receiving low CC-CCD. Multivariate analysis revealed that CC-CCD, T stage, and Epstein–Barr virus (EBV) DNA were independent prognostic factors for DFS (P < 0.05 for all). Patients were further categorized into two prognostic groups by RPA: the low-risk group (T1-3 disease with regardless of EBV DNA, and T4 disease with EBV DNA < 4000 copy/mL), and the high-risk group (T4 disease with EBV DNA ≥ 4000 copy/mL). Significant 5-year DFS improvement was observed for the high-risk group (P = 0.004) with high CC-CCD. However, DFS improvement was relatively insignificant in the low-risk group (P = 0.073).ConclusionsCC-CCD was a positive prognostic factor for responders after NAC in CA-LANPC. Furthermore, CC-CCD ≥ 160 mg/m2 could significantly improve DFS in the high-risk group with CA-LANPC, but the benefit of high CC-CCD in the low-risk group needs further study.

The Combination of T Stage and the Number of Pathologic Lymph Nodes Provides Better Prognostic Discrimination in Early-Stage Cervical Cancer With Lymph Node Involvement.

ObjectiveStage I and II cervical cancer with pelvic and/or para-aortic lymph node (LN) metastases are upstaged to stage IIIC under the new FIGO 2018 staging system, and radical chemoradiotherapy was recommended. But heterogeneity in outcome existed in this group of patients. We conducted this retrospective analysis to evaluate the heterogeneity of these patients and tried to provide a more detailed classification to reflect the prognosis and guide the treatment. We also evaluated the efficacy and toxicity of surgery followed by sequential chemoradiotherapy in this cohort.MethodsEarly-stage cervical cancer with LN involvement that had radical hysterectomy followed by sequential chemoradiotherapy were retrospectively analyzed. Survival analyses were conducted to identify the prognostic factors.ResultsA total of 242 patients were included in the study; 64 (26.4%) patients had treatment failure, and 51 (21.1%) died. Pathology, T stage, the number of pathologic LN (pLN), and neoadjuvant chemotherapy or not were independent prognostic factors for disease-free survival and overall survival (OS). Patients with T1N < 3 pLN had significantly better survival than T2N < 3 pLN/T1-2 N≥ 3 pLN, with failure rates of 11.6% and 35.8% in each group; and 5 year OS was 92% and 62%, respectively (P = 0.000). About 1.5% of the patients discontinued radiotherapy, and 14.1% had G3-4 hematological toxic effects during radiotherapy; 1.7% developed G2-3 lower limb edema, and 2.9% developed severe urinary toxicity.ConclusionNodal involvement alone is inadequate as the sole pathologic factor to predict survival in early-stage cervical cancer. The combination of tumor and node subcategory provides better prognostic discrimination.

Outcomes and Prognostic Factors in Patients with Malignant Peripheral Nerve Sheath Tumor

Objective: To investigate and report the clinical profiles, treatment patterns, and oncologic outcomes in MPNST patients, and to identify the prognostic factors that significantly affect survival.Materials and Methods: Patients diagnosed with and treated for histologically confirmed MPNST at our institute during the January 1997 to June 2018 study period were included. Patient medical records and surgical specimens were reviewed, and study-related data was extracted and analyzed.Results: There were 27 males and 32 females with a mean age of 44 years. Most patients presented with mass and most patients were AJCC stage III. Twenty-nine percent of patients had MPNST that was associated with NF-1. At a median follow-up time, 18 patients (30.51%) suffered from local disease recurrence. Two-year and 5-year overall survival was 72% and 46%, respectively. In univariate analysis, chemotherapy treatment and positive tumor margin were adverse prognostic factors for disease-free survival. In multivariate analysis, chemotherapy treatment (hazard ratio (HR): 3.415, 95% CI: 1.367-16.021; p=0.013) and positive tumor margin (HR: 4.680, 95% CI 1.828-10.314; p=0.014) were found to be independent prognostic factors for disease-free.Conclusion: Chemotherapy treatment and positive tumor margin were identified as independent adverse prognostic factors for disease-free and overall survival, respectively. Accordingly, early detection and appropriate treatment are essential for improved patient outcome.

Dynamic survival analysis of gastrointestinal stromal tumors (GISTs): a 10-year follow-up based on conditional survival

BackgroundThe prognosis of patients with gastrointestinal stromal tumors (GISTs) is generally evaluated at the time of diagnosis but does not reflect the survival dynamics of patients in the future. Therefore, the purpose of this article was to evaluate the conditional survival (CS) of Chinese patients with GISTs after radical resection.MethodsThis retrospective study included 451 patients who underwent radical surgery for GISTs. A Cox proportional hazard model was used to evaluate the prognostic factors of disease-free survival (DFS). The 3-year conditional DFS (CDFS3) of patients who survived for x years was expressed as CDFS3=DFS(x + 3)/DFS(x).ResultsThe traditional 3-year DFS rate decreased gradually from 94.0% at 3 years to 77.3% at 7 years, while the CDFS3 rate increased from 94.0 to 95.2% over the survival time of the patients. In addition, classic clinicopathological prognostic factors had different effects on CDFS3, with changes observed in survival time, but these effects were only slight or moderate (|d|<0.5). Although multivariate analysis showed that age, sex, mitotic index and tumor rupture were independent risk factors for DFS at baseline, all adverse prognostic factors, except for the mitotic index, lost their predictive significance at 5 years after operation. When the Modified NIH criteria were included, the risk staging was found to be an independent risk factor for recurrence or death. Time-dependent Cox regression analysis showed that the modified NIH criteria independently affected the recurrence or death of GIST patients within 2 years after operation.ConclusionCS provides detailed dynamic survival information about Chinese patients with primary resected GISTs. The mitotic index is of great clinical significance for the monitoring and follow-up of patient populations with a high risk of tumor recurrence or death until 5 years after surgery.

Predict Early Recurrence of Resectable Hepatocellular Carcinoma Using Multi-Dimensional Artificial Intelligence Analysis of Liver Fibrosis.

Simple SummaryHepatocellular carcinoma (HCC) is the third most commonly diagnosed cancer in the world, and surgical resection is the commonly used curative management of early-stage disease. However, the recurrence rate is high after resection, and liver fibrosis has been thought to increase the risk of recurrence. Conventional histological staging of fibrosis is highly subjective to observer variations. To overcome this limitation, we used a fully quantitative fibrosis assessment tool, qFibrosis (utilizing second harmonic generation and two-photon excitation fluorescence microscopy), with multi-dimensional artificial intelligence analysis to establish a fully-quantitative, accurate fibrotic score called a “combined index”, which can predict early recurrence of HCC after curative intent resection. Therefore, we can pay more attention on the patients with high risk of early recurrence.Background: Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) microscopy to create a fully quantitative fibrosis score which is able to predict early recurrence. Methods: The study included 81 HCC patients receiving curative intent hepatectomy. Detailed fibrotic features of resected hepatic tissues were obtained by SHG/TPEF microscopy, and we used multi-dimensional artificial intelligence analysis to create a recurrence prediction model “combined index” according to the morphological collagen features of each patient’s non-tumor hepatic tissues. Results: Our results showed that the “combined index” can better predict early recurrence (area under the curve = 0.917, sensitivity = 81.8%, specificity = 90.5%), compared to alpha fetoprotein level (area under the curve = 0.595, sensitivity = 68.2%, specificity = 47.6%). Using a Cox proportional hazards analysis, a higher “combined index” is also a poor prognostic factor of disease-free survival and overall survival. Conclusions: By integrating multi-dimensional artificial intelligence and SHG/TPEF microscopy, we may locate patients with a higher risk of recurrence, follow these patients more carefully, and conduct further management if needed.

HNRNPUL1 inhibits cisplatin sensitivity of esophageal squamous cell carcinoma through regulating the formation of circMAN1A2

Cisplatin (CDDP) is widely used for chemotherapy of esophageal squamous cell carcinoma (ESCC) but the drug resistance limits its therapeutic benefit. Heterogeneous nuclear ribonucleoprotein U-like 1 (HNRNPUL1) belongs to the family of RNA-binding proteins (RBPs) and is involved in DNA damage repair. To investigate whether and how HNRNPUL1 affects CDDP resistance of ESCC, we evaluated the expression of HNRNPUL1 and found that it was associated with recurrence in ESCC patients receiving postoperative platinum-based chemotherapy and was an independent prognostic factor for disease-free survival (DFS). Besides, we showed that the reduced expression of HNRNPUL1 enhanced the CDDP sensitivity of ESCC cells. Furthermore, RNA immunoprecipitation coupled with high-throughput sequencing (RIP-seq) were performed and a range of HNRNPUL1-binding RNAs influenced by CDDP treatment were identified followed by bioinformatics analysis. In terms of mechanism, we found that HNRNPUL1 inhibited CDDP sensitivity of ESCC cells by regulating the CDDP sensitivity-inhibited circular RNA (circRNA) MAN1A2 formation. Taken together, our results first demonstrated the role of HNRNPUL1 in CDDP resistance of ESCC and suggested that HNRNPUL1 may be a potential target of ESCC chemotherapy.

Risk stratification and adjuvant chemotherapy after radical resection based on the clinical risk scores of patients with stage IB-IIA non-small cell lung cancer

IntroductionDespite the heterogeneity among patients with stage IB-IIA non-small cell lung cancer (NSCLC), clinically applicable models to identify patients most suitable for receiving adjuvant chemotherapy (ACT) are limited. We aimed to develop a model for risk stratification and the individualized application of ACT. MethodsBetween January 2008 and March 2018, patients with T2N0M0 NSCLC at Sun Yat-sen University Cancer Center were retrospectively enrolled. Survival curves were estimated by Kaplan-Meier method and compared with log-rank test. Cox regression models were used to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was implemented. Subgroup analysis was performed based on clinical risk score (CRS) value and epidermal growth factor receptor (EGFR) mutation status. ResultsOf 1063 patients with T2N0 NSCLC enrolled, 272 patients received ACT. Before PSM, patients with high CRS (>1) had a significantly worse OS and DFS outcomes. In the PSM, the baseline characteristics of the 270 pairs of patients were well matched. ACT was associated with improved OS outcomes for patients with a high CRS, while ACT was associated with improved OS and DFS outcomes in patients with wild-type EGFR. The interaction analysis showed an apparent interaction effect between ACT and EGFR-activating mutations as well as chemotherapy regimens and histology. ConclusionsThe CRS can predict the prognosis of patients with stage IB-IIA NSCLC. ACT could improve the outcome of patients with a high CRS. Patients with non-squamous cell histology receiving pemetrexed plus platinum might benefit more, but not those with EGFR-activating mutations.

MA04.01 Multimodality Treatment and Outcome in Stage III Thymic Epithelial Tumors (TETs): A Retrospective Analysis From the French RYTHMIC Network

TETs are rare and potentially aggressive malignancies with high associated prevalence of autoimmune disorders (AIDs). Complete resection, pathological subtype according to WHO classification and Masaoka-Koga stage (MK) are the main prognostic factors. MK III represents a heterogeneous population without a clear optimal therapeutic approach, so we have collected outcomes of patients with MK III TETs in a large prospective registry. RYTHMIC is a French network for TETs composed of national and regional expert centers, with the objective of systematic discussion of patient’s management at a single nationwide tumor board, based on consensual guidelines. We conducted a retrospective analysis of MK III TET patients discussed at the RYTHMIC tumor board between January 2012 and December 2019. Data were prospectively collected in a central database. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were determined by Cox proportional hazards modeling. 366 patients with a median age of 61 years (range 16-90) were included; 52% were male. 27% (n=99) of AIDs, mainly Myasthenia Gravis (n=82, 82.8%). Thymoma B2 was the most frequent (n=106, 29%) followed by B3 (n=71, 19.4%), thymic carcinoma (n=56, 15.3%), AB (n=29, 7.9%), B1 (n=28, 7.7%) and, A (n=22, 6%). Tumor invasiveness were mainly reported to lung (n=99, 27%), pleura (n=91, 25%) and pericardium (n=72, 29.7%). TNM classification was available in 60% of patients, among them: T2 (n=70, 19.1%), T3 (n=135, 36.9%), T4 (n=14, 4%). Forty-two (11.5%) and 23 (6.3%) patients reported phrenic nerve (PN) and great vessels invasiveness, respectively. Surgery was performed in 254 patients (69.4%), resection was complete (R0) in 54% including 34.6% (n=88) PN resection; mean tumor size was 72 mm (1-200 mm) post-operative radiotherapy was delivered to 97% (n=169). Among 55 patients initially considered non-surgical candidates, 36 (65.5%) underwent resection after induction chemotherapy, and 10 (2.7%) patients received with definitive radiotherapy. Recurrence was observed in 87 (26%) patients, mainly to the pleura (n=39, 45%). 10-year OS and DFS were 79% and 30%, respectively. Multivariate analysis for DFS is reported in the table 1; no statistical significance results were found for OS.Table 1Clinicopathological prognostic factors for DFSp-valueHR95% C.I. lower95% C.I. upperSex (female)4,9512,09411,708<0,0001Age at Dx0,9760,9531,0010,059AID0,7910,2952,1230,642T2NANANA0,046T31,4630,5164,1470,474T410,4241,60767,6110,014Type A7,1470,431118,4250,17Type ABNANANA0,982Type B10,2390,0252,2810,214Type B22,3390,6098,9910,216Type B30,7780,1663,6370,749Thymic carcinoma43,187,604245,212<0,0001Complete resection0,3110,140,6920,004Adjuvant Radiotherapy0,7710,2362,5180,666Induction Chemotherapy0,3710,1430,9620,041 Open table in a new tab Complete resection after induction chemotherapy improves recurrence outcome of patients with MK III TET, especially for T4. Adjuvant radiotherapy may have a positive impact on DFS. MK III TET patients not candidates for primary surgery should be systematically reassessed for resection after induction chemotherapy.