Disease-free Survival Time Research Articles

Ultra-radical surgery for advanced ovarian cancer: a retrospective cohort study in a tertiary referral cancer center in the UK.

Ovarian cancer is the leading cause of death from gynecological cancer in the UK. The standard of care is a combination of surgery and chemotherapy. The aim of the treatment is the resection of all macroscopic disease. In selected cases of advanced ovarian cancer this is achieved with ultra-radical surgery. However, NICE encourages further research due to low quality evidence on the safety and efficacy of this extensive surgery. The aim of this study was to examine the morbidity and survival rates of ultra-radical surgery for advanced ovarian cancer performed in our unit and compare our findings with the current literature. This is a retrospective study of 39 patients diagnosed with stage IIIA-IV ovarian and primary peritoneal cancer who underwent surgery in our unit between 2012 and 2020. The main outcome measures were the perioperative complications, the disease-free survival, the overall survival rate and the recurrence rate. The study enrolled 39 patients with stages IIIA-IV who were treated in our unit between 2012 and 2020. 21 patients were at stage III (53.8%) whereas 18 (46.1%) at stage IV. 14 patients underwent primary and 25 secondary debulking surgery. Major and minor complications occurred 17.9% and 56.4% of the patients, respectively. Complete cytoreduction following surgery was achieved in 24 cases (61.5%). The mean and the median survival time were 4.8 years and 5 years, respectively. The mean disease-free survival time was 2.9 years while median disease-free survival time was 2 years. Age (P=0.028) and complete cytoreduction (p=0.048) were found to be significantly associated with survival. Primary debulking surgery was significantly associated with lower probability of recurrence (P=0.049). Although the number of patients is relatively small, our study indicates that ultra-radical surgery in centers with high expertise may result in excellent survival rates with an acceptable rate of major complications. All patients in our cohort were operated by an accredited gynecological oncologist and a hepatobiliary general surgeon with a special interest in ovarian cancer. A few cases required input from a colorectal and a thoracic surgeon. We believe that the careful selection of the patients that can benefit from ultra-radical surgery and our model of joint surgery can explain our excellent results. Further research is essential to establish that ultra- radical surgery has an acceptable rate of morbidity for patients with advanced ovarian cancer.

Clinical Analysis of Matched Sibling Donor Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Young Patients with Multiple Myeloma

To investigate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of young patients with multiple myeloma (MM). The clinical data of 8 young patients (median age：46 years) with MM who underwent allo-HSCT from HLA-indentical sibling donors in the First Affiliated Hospital of Chongqing Medical University from June 2013 to September 2021 were collected, and their survival and prognosis were retrospectively analyzed. All the patients were successfully transplanted, and 7 patients could be evaluated the efficacy after transplantation. The median follow-up time was 35.2 (2.5-84.70) months. The complete response (CR) rate was 2/8 before transplantation and 6/7 after transplantation. Acute GVHD developed in 2 cases and extensive chronic GVHD developed in 1 case. Within 100 days, 1 case died of non-recurrent events, and 1-year and 2-year disease-free survival were 6 and 5 cases, respectively. At the end of follow-up, all the 5 patients who survived for more than 2 years survived, and the longest disease-free survival time has reached 84 months. With the development of new drugs, HLA-matched sibling donor allo-HSCT may be a curable treatment for young patients with MM.

Abstract HER2-04: HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0

Abstract Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 Background: Amplification and/or overexpression of the HER2 gene is detected in approximately 15% to 20% of breast cancer (BC) patients. HER2-targeted therapies improve survival in HER2+ BC. Current HER2 diagnostic tests and thresholds were designed and optimized to predict benefit from HER2-directed therapies. The DESTINY-Breast04 trial demonstrated notable efficacy of HER2 antibody-drug conjugate trastuzumab deruxtecan, in patients whose tumors are not conventionally HER2+, but defined as HER2-low (IHC 1 or 2+ without HER2 amplification). A better understanding of the HER2-low phenotype is therefore of critical importance. Methods: Eligible pts were adults with metastatic HER2 IHC (0,1+,2+/FISH negative) BC seen at MD Anderson between 2006 and 2019. Primary biopsy of the breast was used to test biomarkers. HER2 low was defined as IHC 1+ or 2+ and FISH-negative. HER2-negative was defined as HER2 IHC 0. Multi-covariate logistic regression models were used to evaluate effect of clinical factors on HER2 low status and pCR. Overall survival (OS) was defined as time from diagnosis date until death. Disease free survival (DFS) was defined as time from definitive surgery date until the first local/distant recurrence or death from any cause. Patients alive without events (death for OS, recurrence/death for DFS) were censored at last follow-up date. OS and DFS times were estimated by Kaplan-Meier method. Multivariate Cox proportional hazards regression models were applied to assess effect of covariates of interest on OS and DFS. Results: A total of 3053 early stage and 1203 de novo female BC patients were included in the analysis. The prevalence of HER2 low for early stage patients was 59.3% (1811/3053) and for de novo metastatic disease 59.3% (713/1203). In early stage patients, white race, higher nuclear grade and positive ER status were significantly associated with HER2 low status in multicovariate logistic regression. Univariately, pCR rate was significantly associated with negative ER (10.2% in negative vs 2.7% in positive), negative PR (8.6% vs 2%) and negative lymphatic vascular invasion (9.2% vs 2%). Multicovariate logistic regression showed ER (p=0.0124), PR (p=0.0439) status and lymphatic vascular invasion (p< 0.0001) were significantly associated with pCR status. With median follow-up of 8.5 years, median OS time was 5.3 years (95% CI: [4.9, 5.4]), 5.4 years and 4.8 years in HER2 low and HER2 0 groups, respectively. In multicovariate Cox regression, HER2 low was significantly associated with longer OS (HR=0.87, p=0.008), adjusted for age, race, stage, nuclear grade, lymphatic-vascular invasion and ER/PR status. In patients who received neoadjuvant chemotherapy, adjusted for stage, nuclear grade, ER and PR status and pCR, HER2 low was significantly associated with a longer OS time (HR=0.87, p=0.04). Median DFS time was 1.9 years (95% CI: (1.8, 2.0)). Age, stage, histology, nuclear grade, and ER and PR status were significantly associated with DFS by multicovariate Cox regression. Among de novo cases, higher nuclear grade (HR [II vs I]=1.838, p =0.008; HR [III vs I]=1.856, p=0.007) and positive ER status (OR=1.933, p <.0001) were associated with high percentage of HER2 low by multicovariate logistic regression. Median OS time was 3.2 years (95% CI: (3.0, 3.5)). By multicovariate Cox regression, race, histology, nuclear grade, ER and PR status, and HER2 low status (HR=0.834, p=0.0260) were significantly associated with OS time. Conclusions: In metastatic BC pts, HER2 low status was significantly associated with a longer OS and DFS when compared to HER2 0. Nuclear grade and ER positivity was significantly associated with HER2 low status. Biomarkers on recurrence tumor will be presented. This real world data helps to establish the prevalence of HER2 low and their outcomes for this selective cohort. Citation Format: Akshara Singareeka Raghavendra, Diane Liu, Jason Mouabbi, Debu Tripathy. HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-04.

Clinical features and prognosis of patients who undergo renal transplant with urothelial carcinoma.

527 Background: Malignant tumor has been identified as one of the three major causes of death for kidney transplant recipients. This study collected the clinical data of UC patients after kidney transplantation in our center retrospectively, and explored the natural course of disease and response to systemic treatment of this special subgroup of patients. Methods: 1332 consecutive uc patients diagnosed pathologically in our department from 2012 to 2022 were collected, including 26 renal transplant pts. Data were collected, including gender, age, pathological grade, primary site, initial diagnosis stage, metastasis time, site, systemic treatment plan and response to treatment. Kaplan-Meier survival analysis was used to explore the survival and prognostic factors of uc patients after renal transplantation. Results: 1332 consecutive uc patients from Sep 2012 to Sep 2022 in our department were collected, including 26 pts (1.95%) after renal transplantation. 7 males (26.9%).，overall median age of diagnosis 59.0y (40-79y), 24 pathological high-grade (92.3%), 6 cases are with other differentiation (23%), 7 cases (63.65%) her2 IHC 2~3+ in 11 tested cases. Primary site includes 8 renal pelvis (30.8%), 7 ureter (26.9%), 3 bladder (11.5%) and 8 multiple (30.8%). T1, T2, T3, T4 and Tx accounted for 1 (3.8%), 8 (30.8%), 14 (53.8%), 0 and 3 (11.6%)，with lymph node metastasis in 2 (7.7%). Initial stage I, II, III and IV were 3.8%, 69.2%, 11.6% and 15.4% The median survival time of the four groups was 73.4, 38.0, 18.3 and 13.9 months respectively. The median disease-free survival time of 24 patients after radical surgery was 16.0 months (95% CI: 13.2-27.8m), and 11 patients (42.3%) relapsed within one year after surgery. Among systematic treatment, 24, 9 and 3 patients received the first-, second- and third line treatment. First-line includes nab-ptx+gem (7), ptx+gem+endo/bev (6), ptx+gem+cisplatin+endo/bev (4), gem+cisplatin (3), ADC (2 ), gem+carboplatin (1) and gem+oxa (1). Second-line includes nab-ptx based chemo (5), ADC (2), ptx+gem+cisplatin+endo (1) and ptx+sorafenib (1). Third-line includes nab-ptx +gem+cisplatin+bev (1), gem+cisplatin+sotan (1) and everolimus+cisplatin (1). The mPFS of first-, second-, and third-line were 6.5 months (95% CI: 6.4-17.7 m), 2.6 months (95% CI: 1.6-5.3 m) and 2.0 months (95% CI: 1.8-21 m). The mOS was 15.3 months (95% CI: 8.4-15.1 m), 11.6 months (95% CI: 5.0-16.3 m) and 8.0 months (95% CI: 1.6-13.0 m). The most common distant metastasis in late stage included lymph node in 16 cases (61.5%), lung in 12 cases (46.1%), bone in 7 cases (26.9%) and liver in 5 cases (19.2%). Conclusions: Urothelial carcinoma in renal transplant patients has higher degree of malignancy, nearly half of the patients have rapid recurrence and metastasis after operation. It seems these sub-group patients have higher her2 (IHC 2-3+) status.

An extremely rare case of interdigitating dendritic cell sarcoma of the parotid gland with a 40‑month disease‑free survival time after only surgery: A case report.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from dendritic cells and is mainly located in the lymph nodes. To the best of our knowledge, no treatment strategy has yet been established for IDCS, despite its aggressive clinical features. The present study presents the case of a patient with IDCS who experienced a 40-month disease-free survival time after surgery alone. The patient, a 29-year-old woman, presented with a painful right subaural swelling. Diagnostic MRI and 18F-fludeoxyglucose positron emission tomography/computed tomography revealed a right parotid gland tumour and ipsilateral cervical lymph node. The patient underwent surgical resection, and histological examination of the resected tissue specimens confirmed IDCS diagnosis. To the best of our knowledge, this is only the fifth report of an IDCS located in the parotid gland, with the longest follow-up period among cases of IDCS reported in this region. The positive outcome of this patient suggests that surgical resection may be an effective treatment option for local IDCS. Nonetheless, further studies are required to establish a definitive diagnosis and treatment strategy for IDCS.

JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer.

We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). The experimental treatment consisted of 3 cycles of paclitaxel (180mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1months (95% CI 6.5-11.9), while the median overall survival time was 23.2months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

Blood glucose monitoring during surgery in dogs to assess completeness of surgical resection of insulinoma: 11 cases.

To evaluate whether intraoperative detection of rising levels of blood glucose could improve the completeness of resection of insulin-secreting tumor tissue and whether this improves long-term outcomes. 11 client-owned dogs diagnosed with insulinoma. Retrospective review of medical records of dogs undergoing partial pancreatectomy as treatment for insulinoma. A blood glucose reading was obtained at induction, following removal of the pancreatic mass and/or after each suspected metastatic lesion until blood glucose had normalized. Disease-free interval and survival time were measures of outcome. A positive increase in blood glucose was detected in all cases, with a mean rise of 6.35 ± 4.5 mmol/L. Mean follow-up was 611 days, mean disease-free interval was 382 days, and median survival time was 762 days. Tumor stage was not associated with outcome. Three cases underwent a second surgery (metastasectomy), achieving further prolongation of disease-free survival. A sustained increase in intraoperative blood glucose provided the surgeon with confidence of more complete resection of insulinoma tissue and resulted in improved outcomes in all cases included in this study. Subsequent metastasectomy of recurrent insulinoma lesions also provided good outcomes. Intraoperative monitoring of blood glucose during surgical treatment of insulinoma resulted in the surgeon continuing to explore and resect abnormal tissue until an increase of glycemia was observed. This was shown to provide the surgeon with more confidence of resection of all active insulinoma tissue and improved clinical outcomes.

Levels of systemic inflammation response index are correlated with tumor-associated bacteria in colorectal cancer

The relationship between systemic inflammation and tumor-associated bacteria is largely unknown in colorectal cancer (CRC). The primary aim of this study was to investigate the prognostic effects of the systemic inflammation response index (SIRI) on the survival outcomes of CRC patients who experienced surgical therapy, and the second aim was to reveal the potential association between SIRI levels and tumor-associated bacteria in CRC. We recruited a cohort of 298 CRC patients who experienced surgical resection in Wuhan Union Hospital. These patients were assigned to the low and high groups based on the cut-off value of SIRI. We utilized 1:1 propensity score matching (PSM) to reduce the potential confounding factors between the low SIRI group (N = 83) and the high SIRI group (N = 83). The total DNA of 166 paraffin-embedded tumor tissues and 24 frozen tumor tissues was extracted and amplified, and 16 S rRNA sequencing was employed to uncover the composition of microbiota between low and high SIRI groups. Survival analysis uncovered that the high SIRI cohort exhibited significantly shorter overall and disease-free survival time than low SIRI companions after PSM. The ROC analyses showed that the prediction abilities of SIRI were much higher than other serum inflammatory biomarkers for survival outcomes. The microbial richness and diversity in the low SIRI group were remarkably higher than those in the high SIRI group. At the phylum level, we found that Proteobacteria, Synergistetes, WPS-2, Thermil, Fusobacteria were enriched in the high SIRI group. Cupriavidus, Thermus, Ochrobactrum, Cupriavidus, Acidovorax were enriched in the high SIRI group at the genus level. 16 S rRNA based on frozen samples also obtained similar results. SIRI is a promising and novel prognostic biomarker among CRC sufferers who underwent surgical removal. There existed significant differences in the diversity and compositions of tumor-associated bacteria between the low and high SIRI groups.

Hepatic artery resection in distal cholangiocarcinoma.

This study aimed to elucidate the safety and oncological outcomes of surgery with hepatic artery resection (HAR) for patients with distal cholangiocarcinoma. The clinical data of patients with distal cholangiocarcinoma who underwent curative intent surgery at Hiroshima University between March 2009 and January 2021 were retrospectively analyzed. Eligible patients were classified according to the presence or absence of HAR (HAR and non-HAR group), and clinicopathological features and disease-free survival rates were compared between the two groups. Among the 60 patients analyzed, eight patients had received HAR, and the remaining 52 patients had not. The rate of portal vein resection, T stage, and the number of metastasized lymph nodes in the HAR group were significantly greater than those in the non-HAR group (p < 0.001, p = 0.00695, and p = 0.0480, respectively). Postoperative severe complication was confirmed in one patient, and there were no in-hospital deaths in the HAR group. Seven of 8 patients in the HAR group showed recurrence during follow-up, and of those, six patients showed early recurrence within 1year postoperatively. The disease-free survival time in the HAR group was significantly shorter than that in the non-HAR group (median: 7.4m vs. 34.2m, respectively) (p < 0.001). Multivariate analysis revealed that lymph node metastasis and HAR were significant risk factors for predicting the adverse disease-free survival time (hazard ratio (HR), 3.21; p = 0.0142; HR, 4.47; p = 0.0346, respectively). Patients with distal cholangiocarcinoma who underwent surgery with HAR tended to show early recurrences, although HAR could be performed safely.

Survival impact of unexpected N2 in stage IIIB/N2 non-small cell lung cancer patients.

We investigated the effect of unexpected N2 on survival in stage IIIB/N2 cases. We retrospectively analyzed 1803 non-small cell lung cancer patients between 2010 and 2016. There were 89 patients (4.9%) with unexpected N2 (pathological (p) IIIB/N2 group), whereas 49 patients (2.7%) with cN2 (clinical (c) IIIB/N2 group). Although pIIIB/N2 group underwent surgery followed by adjuvant therapy, the cIIIB/N2 group of patients had multimodality treatment including induction chemotherapy ± radiotherapy followed by surgery. The five-year overall survival (OS) for all patients was 36.0% [median survival time (MST) 27.9 months], and disease-free survival (DFS) was 28.9% (MST, 18.2 months). The OS was 39.6% (MST: 34.4 months) and the median DFS time was 31.1% (Median: 23.1 months) in the pIIIB/N2 group, whereas it was 29.2% (MST: 23.0 months) for OS and 22% (median: 12.4 months) for DFS in the cIIIB/N2 group. There were no significant OS and DFS differences between the pIIIB/N2 group and the cIIIB/N2 group (p = 0.124 and p = 0.168, respectively). In stage IIIB/N2 cases, the fact that N2 could not be detected preoperatively with minimally invasive or invasive methods and was detected in the pathological examination after surgery does not provide a survival advantage.

MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.

Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Transcription factors (TFs) are essential gene expression regulators, and play critical roles in cancer development. However, the biological actions and prognostic value of TFs in GC remain unclear. In this study, we identified a risk model based on a 14-TF signature to predict recurrence-free survival in patients with GC. We further analyzed the ability of 14-TF to predict recurrence-free survival time in GC and found that a higher expression level of metastasis-associated protein 2 (MTA2) was associated with shorter overall survival and disease-free survival time in GC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promotes GC growth and metastasis. Furthermore, we identified MTA2 binding to the promoter of minichromosome maintenance deficient 5 (MCM5), thereby promoting GC progression. Overall, these findings strongly support the prognostic potential of the 14-TFs signature and suggest that targeting MTA2 may be a promising strategy to treat GC.

Long-term retroperitoneal lymph node dissection outcomes for nonseminomatous germ cell tumors with postchemotherapy retroperitoneal residual tumors, in a specialized hospital of Saudi Arabia

Abstract Background: In men under the age of 35 years, testicular cancer is the most prevalent solid tumor. Additional treatment is necessary for many people with nonseminomatus germ cell tumors (NSGCTs). Whether in conjunction with chemotherapy or as a stand-alone procedure, retroperitoneal lymph node dissection (RPLND) continues to play a critical role in the treatment of these patients. There is a lack of information in Saudi Arabian literature about the long-term oncologic outcome of NSGCT following RPLND surgery. Objective: The study’s goals were to identify clinical and pathological characteristics related with long-term survival following NSGCT for RPLND, as well as to assess the surgical and oncological results of this treatment. Methodology: From January 2010 to April 2021, nine adults who had had orchidectomy for testicular cancer and RPLND following treatment for the evidence of persistent NSGCT disease at our hospital were included in this retrospective research. Demographic information, laboratory results, radiological findings, staging, chemotherapy and radiotherapy status, surgical procedure details, perioperative problems, morbidity, and mortality were all acquired from patients’ medical records. Rates of disease return and overall survival. SPSS was utilized for the data analysis. Results: During the study period, nine patients with NSGCT underwent RPLND, with a mean age of 28 years (5.4: standard deviation). The most common diseases were yolk sac and embryonal cell cancer. In addition to receiving neoadjuvant chemotherapy, all patients had a Clavien–Dindo score of 2, and there was no mortality after RPLND. Overall median survival time was 26, and disease-free survival time was 21 months. Overall survival at 1 year was 86%, and at 5 years, it was 66%. The prognosis of embryonal cell cancer was more optimistic than that of a tumor of the yolk sac. Conclusion: We have shown that RPLND has an extremely low rate of morbidity and postoperative problems. In terms of oncology, it results in adequate overall and disease-free survival rates, with low morbidity and postoperative complications.

Comprehensive analysis of the PTPN13 expression and its clinical implication in breast cancer.

Protein tyrosine phosphatases non-receptor 13 (PTPN13) could be a potential biomarker in breast cancer (BRCA), but its genetic variation and biological significance in BRCA remain undefined. Hereon, we comprehensively investigated the clinical implication of PTPN13 expression/gene mutation in BRCA. In our study, a total of 14 cases of triple-negative breast cancers (TNBC) treated with neoadjuvant therapy were enrolled, and post-operation TNBC tissues were collected for next-generation sequencing (NGS) analysis (422 genes including PTPN13). According to the disease-free survival (DFS) time, 14 TNBC patients were divided into Group A (long-DFS) and Group B (short-DFS). The NGS data displayed that the overall mutation rate of PTPN13 was 28.57% as the third highest mutated gene, and PTPN13 mutations appeared only in Group B with short-DFS. In addition, The Cancer Genome Atlas (TCGA) database demonstrated that PTPN13 was lower expressed in BRCA than in normal breast tissues. However, PTPN13 high expression was identified to be related to a favorable prognosis in BRCA using data from the Kaplan-Meier plotter. Moreover, Gene Set Enrichment Analysis (GSEA) revealed that PTPN13 is potentially involved in interferon signaling, JAK/STAT signaling, Wnt/β-catenin signaling, PTEN pathway, and MAPK6/MAPK4 signaling in BRCA. This study provided evidence that PTPN13 might be a tumor suppressor gene and a potential molecular target for BRCA, and genetic mutation and/or low expression of PTPN13 predicted an unfavorable prognosis in BRCA. The anticancer effect and molecular mechanism of PTPN13 in BRCA may be associated with some tumor-related signaling pathways.

Circular RNA expression profile identifies circMGEA5 as a novel metastasis-promoting factor and potential biomarker in osteosarcoma.

Osteosarcoma (OS) is associated with a high incidence of lung metastasis, which leads to a high risk of cancer death. Circular RNA (circRNA), a novel class of noncoding RNA, is emerging as a key player in human cancer. Herein, we explored the role of circMGEA5 in OS metastasis by conducting circRNA expression microarray. CircMGEA5 was significantly upregulated in metastatic OS tissues compared to primary tissues. High circMGEA5 was positively related with shorter overall and disease-free survival time. Knockdown of circMGEA5 suppressed OS cell migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, circMGEA5 acted as a competing endogenous RNA (ceRNA) to directly sponge miR-153-3p and miR-8084, resulting in increasing ZEB1 and Snail expression, respectively, thereby inducing EMT and metastasis. In turn, ZEB1 and Snail were capable to bind to circMGEA5 promoter, activating circMGEA5 transcription, thus forming a positive feedback loop. Furthermore, we established the tail vein injection model and found that circMGEA5 depletion remarkably reduced lung metastasis nodules generated by OS cells. In sum, our findings, for the first time, reveal the metastasis-promoting role of circMGEA5 in OS. Targeting of this newly identified ceRNA axis may be crucial in the development of novel therapies for metastatic OS patients.

Construction and validation of a novel cuproptosis-related long noncoding RNA signature for predicting the outcome of prostate cancer.

Background: Prostate cancer (PCa) is one of the most common tumors of the urinary system. Cuproptosis is a novel mode of controlled cell death that is related to the development of various tumor types. However, the functions of cuproptosis-related long noncoding RNAs (CRLs) in PCa have not yet been well studied. Methods: In this study, data of PCa patients were obtained from The Cancer Genome Atlas (TCGA) and from the Changhai Hospital. Univariate and multivariate Cox regression analyses and LASSO regression analysis were conducted to screen CRLs linked to the prognosis of PCa patients. A risk score model was constructed on the basis of CRLs to predict prognosis. PCa patients were categorized into high- and low-risk cohorts. The predictive value of the risk score was evaluated by Kaplan-Meier survival analysis, receiver operating characteristic curves, and nomograms. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore possible pathways involving CRLs in PCa. Immune function analysis confirmed the correlation between CRLs and immunity in PCa. Finally, we explored the tumor mutational burden and drug response in the high- and low-risk cohorts. Results: First, we identified seven CRLs (C1orf229, C9orf139, LIPE-AS1, MCPH1-AS1, PRR26, SGMS1-AS1, and SNHG1) that were closely related to prognosis in PCa. The risk score model based on the selected CRLs could accurately predict the prognosis of PCa patients. The high-risk cohort was associated with worse disease-free survival (DFS) time in PCa patients (p < 0.001). ROC curve analysis was performed to confirm the validity of the signature (area under the curve (AUC) at 1year: 0.703). Nomograms were constructed based on the risk score and clinicopathological features and also exhibited great predictive efficiency for PCa. GO and KEGG analyses showed that the CRLs were mainly enriched in metabolism-related biological pathways in PCa. In addition, immune function analysis showed that patients in the high-risk cohort had higher TMB and were more sensitive to conventional chemotherapy and targeted drugs including doxorubicin, epothilone B, etoposide, and mitomycin C. Conclusion: We constructed a novel CRL-related risk score model to accurately predict the prognosis of PCa patients. Our results indicate that CRLs are potential targets for drug therapy in PCa and provide a possible new direction for personalized treatment of PCa patients.

Hepatic artery lymph node relevance in periampullary tumors: A retrospective analysis of survival outcomes.

The Periampullary area comprehends a heterogeneous and complex structure with different histological tissues. Surgical standards include the peripancreatic regional lymphadenectomy, and during pancreatoduodenectomy (PD) the hepatic artery lymph node HALN(8a) is dissected. We aimed to describe the prognostic significance of the HALN(8a) lymph node metastasis in terms of disease-free survival (DFS) and overall survival (OS) in a specific cohort of patients in limited economic and social conditions. A retrospective study was conducted based on a prospective database from the HPB department of patients who underwent pancreaticoduodenectomy (PD) due to periampullary tumors during 2014-2021. Overall survival (OS) and disease-free survival (DFS) were estimated to be associated with positive HALN(8a) using Kaplan-Meier analysis. Log Rank test and Cox proportional hazards regression analysis was used. 111 patients were included, 55,4% female. The most frequent pathology was ductal adenocarcinoma (60.3%). The positive rate of the HALN(8a) node was 21.62%. The Median OS time was 25.5 months, and the median DFS time was 13,8 months. Positive HLAN(8a) node, the cutoff of lymph node ratio resection (LNRR), and vascular invasion showed a strong association with OS. (CoxRegression p = 0.03 HR 0.5, p 0.003 HR = 1.8, p = 0.02 HR 0.4 CI 95%). In terms of DFS, lymph node ratio cutoff, tumoral size, and vascular invasion showed a statistically significant association with the outcome (p = 0.008, HR = 1.5; p = 0.04 HR = 2.1; p = 0.02 HR = 0.4 CI 95%). In this series of PD, OS was reduced in patients with HALN(8a) compromise in patients with pancreatic cancer, however without statistical significance in DFS. In multivariate analysis, lymph node status remains an independent predictor of OS and DFS. Further studies are needed.

Long-term results of postoperative unsuspected small cell lung cancer on real-world data

BackgroundIn traditional opinion, solid pulmonary nodule suspected lung cancer should be confirmed by pathology before the operation to exclude small cell lung cancer (SCLC), considering SCLC tends to be aggressive and surgical effect in the management of SCLC remains controversial. The aim of this study was to evaluate the survival result and risk factors of postoperative unsuspected SCLC.MethodsA total of 120 patients with postoperative unsuspected SCLC who were confirmed by pathology and referred to Chinese PLA General Hospital between 2000 and 2021 were retrospectively analyzed (surgery group). Additionally, 120 patients with limited-stage SCLC who underwent chemotherapy and radiotherapy in the same period were enrolled in the chemoradiotherapy group.. Kaplan–Meier method was used to estimate survival; the Log-Rank test was used to compare survival rates between different groups; a COX stepwise regression model was used for multivariate analysis.ResultsAmong 120 patients in the surgery group, 28 were with central type and other 92 with peripheral type. The median survival (OS) was 44.85 months, and the 5-year survival rate was 46%. The 5-year survival rates for stage I, II, and III were 52.1%, 45.4%, and 27.8%, respectively. The mean disease-free survival time (DFS) was 30.63 ± 4.38 months, and the 5-year DFS rate was 31.5%. In the chemoradiotherapy group, the mean OS was 21.4 ± 4.26 months, and the 5-year survival rate was 28.3%. The 5-year survival rates for clinical stage I, II, and III were 42.5%, 39.8%, and 20.5%, respectively. The mean progression-free survival (PFS) was 10.63 ± 3.6 months. In the surgery group, one-way ANOVA revealed that the gender, symptoms, smoking history, tumor location, and postoperative radiotherapy were not associated with OS (P ≥ 0.05), while age, surgical approach, surgical method, N stage, TNM stage, and vascular tumor thrombus were related to OS (P < 0.05). Multivariate analysis indicated that the N stage was associated with OS (HR = 1.86 P = 0.042).ConclusionSurgery and adjuvant therapy were found to have encouraging outcomes in postoperative unsuspected SCLC. Patients with stage I, stage II and part of stage IIIA SCLC could benefit from surgery and the standard lobectomy, and systematic lymph node dissection, is also recommended for these patients.

Outcomes and Management of Head and Neck Cancer at a South Indian Cancer Centre: A Retrospective Study

Abstract Introduction Head and neck cancers are one of the most common cancers in the Indian subcontinent. The trends of these cancers worldwide have drastically changed over the past 15 years. In spite of all the new technology and timely diagnosis, the treatment of these cancers is still a challenge. These cancers still continue to be a significant cause of morbidity and mortality worldwide. Objectives To identify different patterns of care received by patients with primary head and neck cancer in a single center and analyze the outcomes of the different patterns of care received by these patients in terms of overall survival and disease-free survival. Materials and Methods We included 707 patients with primary head and neck cancer registered and treated in our institution from January 2015 to December 2017. The demographic details of the patient, treatment received, and outcomes of treatment were collected retrospectively from our hospital's medical registry. Descriptive analysis was performed by calculating mean and standard deviation for quantitative variables, whereas frequency and proportion were calculated for categorical variables. The mean/median overall survival and recurrence-free survival were compared across various explanatory parameters using log rank–test. A p-value &lt; 0.05 was considered statistically significant. Results A total of 707 patients were included in the final analysis. The median age of presentation was 60 years. In total, 50% of patients presented with stage IV disease at diagnosis and 78% had a history of smoking or other tobacco use. Oral cavity was the most common primary site. Concurrent chemotherapy with radiation therapy was the most common modality of treatment used in 49% of patients: RT was the common modality of treatment in 21% patients. Fourteen percent patients were treated by only surgery. All patients who underwent treatment were included for survival analysis, which showed that the median overall survival time was 42 months (34–49 months). The median duration of disease free-survival time was 37 months (30–43 months). Conclusion In our study, most patients presented with locally advanced disease. Multimodality treatment yielded better results. Based on our study, in early-stage cancer, where single modality treatment was used, adjuvant therapy should be tailored based on nomogram.

C-Reactive Protein Pretreatment-Level Evaluation for Ewing's Sarcoma Prognosis Assessment-A 15-Year Retrospective Single-Centre Study.

A pathological/inflamed cellular microenvironment state is an additional risk factor for any cancer type. The importance of a chronic inflammation state in most diffuse types of tumour has already been analysed, except for in Ewing's sarcoma. It is a highly malignant blue round cell tumour, with 90% of cases occurring in patients aged between 5 and 25 years. Worldwide, 2.9 out of 1,000,000 children per year are affected by this malignancy. The aim of this retrospective study was to analyse the role of C-reactive protein (CRP) as a prognostic factor for Ewing's sarcomas. This retrospective study at Klinikum rechts der Isar included 82 patients with a confirmed Ewing's sarcoma diagnosis treated between 2004 and 2019. Preoperative CRP determination was assessed in mg/dL with a normal value established as below 0.5 mg/dL. Disease-free survival time was calculated as the time between the initial diagnosis and an event such as local recurrence or metastasis. Follow-up status was described as death of disease (DOD), no evidence of disease (NED) or alive with disease (AWD). The exclusion criteria of this study included insufficient laboratory values and a lack of information regarding the follow-up status or non-oncological resection. Serum CRP levels were significantly different in patients with a poorer prognosis (DOD) and in patients who presented distant metastasis (p = 0.0016 and p = 0.009, respectively), whereas CRP levels were not significantly different in patients with local recurrence (p = 0.02). The optimal breakpoint that predicted prognosis was 0.5 mg/dL, with a sensitivity of 0.76 and a specificity of 0.74 (AUC 0.81). Univariate CRP analysis level &gt;0.5 mg/dL revealed a hazard ratio of 9.5 (95% CI 3.5-25.5). In Ewing's sarcoma cases, we consider a CRP pretreatment value &gt;0.5 mg/dL as a sensitive prognostic risk factor indication for distant metastasis and poor prognosis. Further research with more data is required to determine more sensitive cutoff levels.

Higher thymocyte selection-associated high mobility group box (TOX) expression predicts poor prognosis in patients with ovarian cancer

BackgroundOvarian cancer is one of the most lethal gynecologic malignancies with a dismal prognosis that poses a serious threat to human health, highlighting the need for more knowledge about what is required for identifying some biomarkers for early diagnosis, prediction of prognosis and disease monitoring. TOX, a critical transcription factor related to the development of malignancies that contributing to lymphocytes not just T cells, had been proved prognostic value in some spectrum of cancers. Here, we aimed to study the prognostic role of TOX in ovarian cancer.ResultsWe found that TOX was not only expressed in CD8 T cells but also tumor cells. TOX expression score was higher in ovarian cancer tissues and correlated with survival status. Survival analysis revealed that ovarian cancer patients with high TOX expression score generally shorter overall survival and disease-free survival times. Univariate and Multivariate Cox demonstrated that TOX expression score could be used as an independent prognostic factor for patients with ovarian cancer.ConclusionTOX expression in ovarian cancer could be a promising tool for predict overall survival of ovarian cancer patients.