Exploration of Extracellular Vesicle Long Non-Coding RNAs in Serum of Patients with Cervical Cancer.

INTRODUCTION: Cervical cancer (CC) is the fourth most common cancer type and a leading cause of cancer-related deaths in women worldwide. Its underlying molecular mechanisms are unclear. Cancer cell-derived extracellular vesicles (EVs) are involved in cancer development and progression by delivering regulatory factors, including microRNAs and long non-coding RNAs (lncRNAs). METHODS: Here, we identified the EV lncRNA expression profiles associated with different developmental stages of CC using next-generation sequencing. EVs from the serum of patients with stages I-III CC and healthy donors were characterized using EV marker immunoblotting and transmission electron microscopy. RESULTS: The EV concentration increases with progression of the disease. Most particles had a 100-250-nm diameter, and their sizes were similar in all groups. We identified many lncRNAs that were uniquely and differentially expressed (DE) in patients with different stages of CC. The pathway analysis results indicated that the upregulated DE EV lncRNAs abundant in stages I and II were associated with cell proliferation and inflammation and cancer progression pathways, respectively. LINC00941, LINC01910, LINC02454, and DSG2-AS1 were highly expressed, suggesting poor overall survival of CC patients. Interestingly, DSG2-AS1 was associated with the human papillomavirus infection pathway through AKT3, DLG1, and COL6A2 genes. CONCLUSION: This is the first study that reports the levels of EVs and their lncRNA contents change during cancer development, demonstrating the existence of a unique vesicle-mediated cell-to-cell communication network underlying cancer progression.

Proteomic analysis of small extracellular vesicles unique to cervical cancer.

Background: Cervical cancer (CC) is the fourth most common cancer in females worldwide. Existing biomarkers for CC, such as squamous cell carcinoma antigens, show low specificity. Hence, a novel biomarker for the diagnosis of CC is required. Through proteomic analysis, this study aimed to distinguish between the small extracellular vesicle (sEV) protein profiles of healthy controls (HC) and CC sera and to identify potential sEV proteins that can serve as biomarkers for CC diagnosis. Methods: The number and size distribution of sEVs in HC and CC sera were measured using nanoparticle tracking analysis. Differential ultracentrifugation combined with size-exclusion chromatography was used to isolate and purify sEVs. Liquid chromatography-tandem mass spectrometry was used to identify and compare the protein profiles between patients with CC and HC. Differentially expressed extracellular vesicle (EV) proteins were validated using The Cancer Genome Atlas database. Results: The EV particle concentration in patients with CC was marginally higher than that in HC. Proteomic and functional protein analyses revealed a difference in the EV protein profiles between HC and CC and identified proteins that can serve as biomarkers for CC. Conclusions: This study provides insights into the potential of sEVs as less invasive biomarkers for CC diagnosis. Validation with a well-designed cohort should be performed to determine the clinical diagnostic value of specific protein markers for CC.

Association between Resting Heart Rate and Oncological Outcomes in Patients with Early-Stage Cervical Cancer Who Have Undergone Radical Hysterectomy with Pelvic Lymphadenectomy.

INTRODUCTION: A few studies have explored the association of resting heart rate (RHR) with mortality and/or other oncological outcomes in patients with specific cancers such as breast, colorectal, and lung cancer. This study aimed to evaluate the association between the RHR and oncological outcomes in patients with early-stage cervical cancer (CC) who underwent radical surgical resection. METHODS: We included 622 patients with early-stage CC (stages IA2-IB1). The patients were divided into four groups based on the RHR as follows: quartile 1, ≤64; quartile 2, 65-70; quartile 3, 71-76; and quartile 4, >76 beats per min (bpm), with the lowest quartile being the reference group. We evaluated the associations of the RHR and clinicopathological features with oncological outcomes using Cox proportional-hazards regression. RESULTS: There were clear among-group differences. Further, there was a significant positive correlation of RHR with tumor size and deep stromal invasion. Multivariate analysis revealed that RHR was an independent prognostic factor for disease-free survival (DFS) and overall survival (OS). Compared with patients with an RHR ≤70 bpm, those with an RHR of 71-76 bpm had a 1.84- and 3.05-times higher likelihood of DFS (p = 0.016) and OS (p = 0.030), respectively, while those with RHR >76 bpm had a 2.20-times higher likelihood of DFS (p = 0.016). CONCLUSION: This is the first study to demonstrate that RHR may be an independent prognostic factor for oncological outcomes in patients with CC.

Clinical Outcomes and Their Prognostic Factors among Cervical Cancer Patients with Bone Recurrence.

Background: Bone recurrence occurs in 0.75%-8% of cervical cancer patients after primary treatment. Only a few previous studies have reported on survival times associated with prognostic factors for bone recurrent cervical cancer. This study aimed to evaluate the oncological outcomes and their predictors among cervical cancer patients with bone recurrence. Methods: The medical records of cervical cancer patients with bone recurrence who received primary treatment at Songklanagarind Hospital from January 2002 to December 2017 were retrospectively reviewed. Prognostic factors were identified using a Cox regression model. Results: The study included 6,354 cervical cancer patients, of whom 98 (1.54%) had bone recurrence at a median time of 25 months after the primary treatment (range 4.9-136 months). The most frequent site of bone recurrence was the spine (81.00%); the two most common visceral coexisting recurrence sites were the lungs and the liver. The median recurrence-free interval (RFI) was 21 months. Of the patients with recurrence, 75 (76.50%) were treated with combined radiation therapy and chemotherapy. The one-year overall survival (OS) after recurrence was 22.70%. On multivariate analysis, age under 60 years at the time of recurrence diagnosis (hazard ratio [HR] = 2.48, 95% CI = 1.47-4.18, p=0.001) and an RFI less than 21 months (HR = 1.63, 95% CI = 1.04-2.55, p=0.03) were independent prognostic factors for OS after recurrence. Conclusion: Bone recurrence in cervical cancer patients is rare and is associated with poor survival. Our study found that age and RFI were significant prognostic factors for OS in cervical cancer patients with bone recurrence.

Microsatellite instability and oncological outcomes in Thai patients with endometrial cancer.

Here, we determined the frequency of microsatellite instability (MSI) and the impact of MSI-high (MSI-H) on clinical outcomes of Thai patients with endometrial cancer (EC). Tissue samples of 110 Thai patients with EC, who had undergone surgical staging, were tested for mismatch repair (MMR) gene deficiency, and the patients were grouped into MSI-H and MSI-stable (MSI-S) groups; 24.5% had MSI-H. Unlike MSI-S group patients, MSI-H group patients had synchronous and metachronous cancer. They showed better 3-year disease-free survival (DFS) than those in the MSI-S group (p=.182; 92.3% vs. 82.6%). The 3-year overall survival was 96.2% in MSI-H and 86.4% in MSI-S groups (p=.163). Multivariate analyses showed lower uterine involvement (p=.004), myometrial invasion ≥50% (p=.032), lymphovascular space invasion (p<.001) and MSI-S (p=.006) as prognostic factors for DFS. Our study showed that the prevalence of MMR gene deficiency in Thai patients with EC is common and associated with better outcomes.Impact StatementWhat is already known on this subject? Microsatellite instability (MSI) occurs in approximately 20-40% of endometrial cancer (EC) cases. MSI analysis in EC can identify patients at higher risk of hereditary nonpolyposis colorectal cancer and those having prognostic factors. Additionally, it is predictive of immune checkpoint inhibitor treatment. However, current evidence shows a correlation between clinicopathological characteristics and EC prognosis. Studies on EC and MSI status effect on survival outcome have yielded inconsistent results regarding the pathological significance of MSI in such malignancies.What do the results of this study add? The prevalence of mismatch repair (MMR) gene deficiency in Thai patients with EC is common (24.5%) and associated with better outcomes.What are the implications of these findings for clinical practice and/or further research? This study highlights the prevalence and impact of MSI on oncological outcomes in patients with EC in a low-incidence country. Future studies should focus on the detection of germline mutation to understand the accurate prevalence of Lynch syndrome in Thai patients with EC.

Predictive Value of the Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) Index on the Oncological Outcomes of Locally Advanced Cervical Cancer Patients.

Purpose: The oncological outcomes of locally advanced cervical cancer (LACC) patients after treatment are poor and heterogeneous. This study aimed to determine the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) inflammatory index in predicting oncological outcomes in LACC patients. Patients and Methods: A total of 1588 LACC patients who received radiation therapy or concurrent chemoradiation were divided into training and test sets. Characteristics, survival, and a HALP cutoff determined by X-tile software were used to build predictive survival models on the training data. Validation of the model was performed on both sets. Results: Patients with a HALP score ≤22.2 tended to have lower age (p < 0.001), lower comorbidity rate (p = 0.016), lower body mass index (p < 0.001), higher stage (p < 0.001), larger tumor size (p < 0.001), and higher likelihood to receive radiation alone than concurrent chemoradiation (p < 0.001). Survival analysis demonstrated that HALP >22.2 was independently associated with better progression-free survival (PFS; hazard ratio; HR 0.55) and overall survival (OS; HR 0.43). Validation of survival prediction by receiver-operating characteristics demonstrated a significantly improved area under the curve of survival prediction in both sets (p < 0.001) after the addition of the HALP index to the model. Conclusion: A lower HALP score was an independent predictive factor for poorer oncological outcomes. The addition of the HALP index can improve the accuracy of predicting the oncological outcomes of LACC patients.

Impact of chemotherapy cycles on oncological outcomes in elders with locally advanced cervical cancer treated with concurrent chemoradiotherapy.

INTRODUCTION: To investigate the association between chemotherapy (CMT) cycles and oncological outcomes in elders with locally advanced cervical cancer (LACC) who treated with concurrent chemoradiotherapy (CCRT). METHODS: We retrospective studied 498 elders with LACC who treated with radiotherapy (RT) or CCRT between 2002 and 2018. Patients were divided into three groups: RT, CCRT with 1-4 and CCRT with 5-6 cycles of CMT. We compared progression-free survival (PFS) and overall survival (OS) among the three groups and explored survival prognostic factors via multivariate analysis and time-varying analysis effect. RESULTS: There were 453 eligible patients; 222, 119 and 112 patients who received RT, CCRT with 1-4 and CCRT with 5-6 cycles of CMT, respectively. Patients in the RT group had older age, poorer performance status, more treatment with conventional RT technique and earlier treatment year comparing with both CCRT groups. Patients who received 5-6 cycles of CMT were less to have underweight, comorbidities and anaemia compared with the RT group. There were patients with lower FIGO stage in 5-6 cycles than in 1-4 cycles of CMT and RT groups. The 5-year PFS and OS between RT, CCRT with 1-4 and CCRT with 5-6 cycles of the CMT group were significantly different. Performance status, comorbidity, histology, FIGO stage and total received 5-6 CMT cycles were significant prognostic factors of PFS and OS. However, the benefits of receiving 5-6 CMT cycles were evidenced only within the first 2.5 years. CONCLUSION: Elders with LACC who received 5-6 cycles of CMT concurrently with RT can improve PFS and OS, but the benefit persisted only within the first 2.5 years.

Molecular insights and clinical impacts of extracellular vesicles in cancer.

Cell-to-cell communication is a pivotal aspect of cancer biology. Recently, extracellular vesicles (EVs)have been shown to play essential roles in intercellular communications between cancer cells and the surrounding microenvironment owing to cancer development. EVs are small membrane-bound vesicles secreted by various cells containing proteins, lipids, mRNAs, and non-coding RNAs (microRNAs and long non-coding RNAs), which contribute to cancer cell development and progression. Here, we provide an overview of current research direction on EVs, especially biomolecules in EVs, and also point out the novel diagnostics, monitoring, predicting, and therapeutic aspects using EVs against cancer.

Safety and Prognostic Impacts of Ovarian Preservation during Radical Hysterectomy for Early-Stage Adenocarcinoma and Adenosquamous Cervical Cancer.

OBJECTIVE: To identify the incidence of ovarian metastasis and the impact of ovarian preservation on oncological outcomes for early-stage adenocarcinoma and adenosquamous cervical cancer. METHODS: 281 patients with stages IA2-IB1 adenocarcinoma and adenosquamous cervical cancer who underwent radical hysterectomy with pelvic lymphadenectomy (RHND) were included in the study. The incidence of ovarian metastasis was evaluated from 173 patients who underwent oophorectomy during RHND. Subgroup analysis was performed for patients less than 50 years (196 of 281 patients) who were classified into two groups, ovarian preservation and nonovarian preservation groups. 5-year recurrence-free survival (5-yr RFS) and 5-year overall survival (5-yr OS) were evaluated and compared between these groups. RESULTS: There was no evidence of ovarian metastasis, synchronous ovarian cancer, or ovarian recurrence during follow-up. In patients less than 50 years of age, there were no statistically significant differences in the 5-yr RFS (P = 0.363), or 5-yr OS (P = 0.974) between the ovarian preservation and nonovarian preservation groups. In Kaplan-Meier analysis, the ovarian preservation group seemed to have a slightly better OS in long-term follow-up (after 15 years); however, the difference was not statistically significant. CONCLUSIONS: Ovarian preservation was safe in adenocarcinoma and adenosquamous cervical cancer stages IA2-B1. However, the impact of ovarian preservation on oncological outcomes needs to be further investigated.

Cost-utility analysis of adjuvant chemotherapy after concurrent chemoradiation in patients with locally advanced cervical cancer.

INTRODUCTION: This study aimed to compare the cost utility of concurrent chemoradiation (CCRT) to CCRT followed by adjuvant chemotherapy (CCRT/ACT) in locally advanced cervical cancer (LACC) using provider and societal viewpoints. METHODS: Data from our trial which was a multi-centre study evaluating the efficacy of ACT compared to CCRT/ACT were entered into a decision tree model. The data included clinical probability, direct medical and non-medical costs, and utility obtained from the patients. The total cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were estimated for a time horizon of 3 years. All costs and outcomes were discounted at 3% annually. RESULTS: The cost of CCRT and CCRT/ACT was approximately 3,058 and 6,896 USD and 4,309 and 7,480 USD from provider and from societal viewpoints, respectively. The QALYs for CCRT and CCRT/ACT were 2.31480 and 2.32045, respectively. The ICER was 569,575 USD per QALY. For stage III-IVA LACC, the ICER was 28,050 USD per QALY. In the sensitivity analysis, the cost of ACT was the most significant influential parameter on the ICER. The ICER would be 0.26-fold lower if the cost of ACT was reduced by 25%. At the current ceiling threshold of 5,000 USD/QALY, CCRT had a 100% probability of being the best option. CONCLUSIONS: In the Thai context, CCRT is more cost effective than CCRT/ACT for stage IIB-IVA LACC. CCRT/ACT may be considered only for stage III-IVA LACC because it has a lower ICER than other types of LACC.

Impact of Obesity on Clinical Outcomes in Patients with Early-Stage Cervical Cancer after Radical Hysterectomy with Pelvic Node Dissection.

BACKGROUND: The aim of this study was to determine the prognostic role of obesity on oncological outcomes, surgical complications, and postoperative morbidity of patients with early-stage cervical cancer. METHODS: Between 2000 and 2016, we enrolled 500 patients with early-stage cervical cancer who underwent radical hysterectomy with pelvic node dissection (RHND) at Songklanagarind Hospital. For analysis, patients were divided based on their body mass index (BMI) into under-normal weight (<25 kg/m2), overweight (25-29.99 kg/m2), and obese (≥30 kg/m2) groups. RESULTS: The median age was 47 years, and the median BMI was 24.3 kg/m2 (25% quartile, 22.0 kg/m2; 75% quartile, 27.4 kg/m2). Patients in the obese and overweight groups were more likely to have comorbidities and adenocarcinoma than patients in the under-normal weight group. The median operative time (OT) was significantly longer in the obese and overweight groups than in the under-normal weight group. The 5-year recurrence-free survival (RFS) of the under-normal weight, overweight, and obese groups was 87.5, 86.2, and 97.6%, respectively, and the 5-year overall survival (OS) times were 95.8, 97.8, and 100%, respectively. There were no significant differences in RFS or OS among the 3 weight groups. Multivariate analysis did not identify BMI as a prognostic factor for RFS and OS. CONCLUSIONS: A high BMI was not associated with increased surgical complications or postoperative morbidity; furthermore, it was not associated with the prognosis of patients with early-stage cervical cancer after RHND. However, it was associated with adenocarcinoma and longer OT.

A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001.

Predictive Factors of Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer.

BACKGROUND: Pelvic lymphadenectomy, which is the routine surgical treatment for early-stage cervical cancer, causes serious morbidity. The goal of the current retrospective study was to identify predictive factors of lymph node metastasis (LNM) in patients with early-stage cervical cancer. PATIENTS AND METHODS: The study included 496 patients diagnosed with stages IA2-IB1cervical cancer who underwent a radical hysterectomy with pelvic lymphadenectomy. The predictive factors of LNM were evaluated. RESULTS: The incidence of LNM in this study was 4.6%. LNM was more common in patients with deep stromal invasion (DSI), tumor size > 2 cm, lymph vascular invasion and parametrial involvement (PI). Multivariate analysis showed DSI (p = 0.010) and PI (p = 0.005) were independently associated with LNM. The median follow-up time was 56.9 months. The patients with LNM had poorer 5-year overall survival (77.8%; 95% confidence interval (CI) 44.2-92.6) than the patients without LNM (98.2%; 95% CI 95.6-99.2; p = 0.002) and also poorer 5-year recurrence-free survival (65.5%; 95% CI 38.6-82.8) than the patients without LNM (90.2%; 95% CI 86.5-92.9; p < 0.001). CONCLUSION: The predictive factors of pelvic lymph node metastasis in stage IA2-IB1 cervical cancer patients were DSI and PI. LNM was associated with poorer oncological outcomes.

Preoperative Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Are Not Clinically Useful in Predicting Prognosis in Early Stage Cervical Cancer.

BACKGROUND: An objective of this study was to determine the prognostic role of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with cervical cancer (CC) stages IA2-IB1. METHODS: The study included 484 patients who underwent radical hysterectomy with pelvic node dissection. The associations of preoperative NLR and PLR with clinicopathologic characteristics and oncological outcomes were analyzed. The cut-off values of NLR (=1.8) and PLR (=119) were set as medians. RESULTS: The clinicopathologic analysis showed that NLR was associated with age (p=0.010), tumor size (p=0.045), and adjuvant treatment (p=0.005), and PLR was associated with only adjuvant treatment (p=0.033). DFS and OS were not significantly different between patients with high and low NLR (p=0.670 and p=0.934) or high and low PLR (p=0.780 and p=0.306). The independent prognostic factors associated with OS were lymph node status and anemia, and with DFS were histology, deep stromal invasion, and lymph node status. CONCLUSIONS: NLR and PLR have no use as prognostic biomarker for DFS and OS in early-stage CC. However, NLR and PLR might be of use in determining the risk for adjuvant treatment.

Fear of cancer recurrence and its predictors among cervical cancer survivors.

OBJECTIVE: To identify the characteristics of fear of cancer recurrence (FCR) in cervical cancer survivors (CCSs) and investigate the relationship of FCR with demographic and medical characteristics, level of quality of life (QOL), and psychological distress. We also aimed to determine the predictors of FCR. METHODS: The short version of the Fear of Progression Questionnaire (FoP-Q-SF), the Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-Cervical (FACT-Cx) questionnaire were administered to 699 CCSs who had complete treatment at Songklanagarind Hospital between 2006 and 2016. Analysis was performed to determine potential predictors associated with FCR. RESULTS: Among the 12 items of the FoP-Q-SF, the 3 greatest fears were 1) worrying about what would happen to their family; 2) being afraid of pain; and 3) fear of disease progression. The prevalences of anxiety and depression disorder were 20.46% and 9.44%, respectively. CCSs who had FCR at the 5th quintile were more likely to have medical co-morbidities, low FACT-Cx scores in all domains and a high HADS scores (anxiety and depression disorder). Multivariate analysis showed that only anxiety disorder (odds ratio [OR]=4.99; p<0.001) and low FACT-Cx score (total) (OR=6.14; p<0.001) were identified as independent predictors for FCR at the 5th quintile. CONCLUSION: FCR is an important problem in cervical cancer which should be addressed during post-treatment care. Only anxiety disorder and low QOL were independently associated with high FCR.

Impact of time interval between radical hysterectomy with pelvic node dissection and initial adjuvant therapy on oncological outcomes of early stage cervical cancer.

OBJECTIVE: To determine the impact of time interval (TI) from radical hysterectomy with pelvic node dissection (RHND) to adjuvant therapy on oncological outcomes in cervical cancer. METHODS: The study included 110 stage IA2-IB1 cervical cancer patients who underwent RHND and adjuvant therapy. The patients were divided into 2 groups based on the cut-off points of TI of 4 and 6 weeks, respectively. The associations of TI and clinicopathologic factors with oncological outcomes were evaluated using Cox proportional-hazards regression. RESULTS: The median TI was 4.5 weeks. There were no statistical differences in 5-year recurrence-free survival (RFS) (89.2% vs. 81.0%, and 83.2% vs. 100.0%) or 5-year overall survival (OS) rates (90.9% vs. 97.2%, and 93.2% vs. 100.0%) between patients according to TI (≤4 vs. >4, and ≤6 vs. >6 weeks, respectively). Deep stromal invasion (p=0.037), and parametrial involvement (PI) (p=0.002) were identified as independent prognostic factors for RFS, together with the interaction between TI and squamous cell carcinoma histology (p<0.001). In patients with squamous cell carcinoma, a TI longer than 4 weeks was significantly associated with a worse RFS (hazard ratio [HR]=15.8; 95% confidence interval [CI]=1.4-173.9; p=0.024). Univariate analysis showed that only tumor size (p=0.023), and PI (p=0.003) were significantly associated with OS. CONCLUSION: Delay in administering adjuvant therapy more than 4 weeks after RHND in early stage squamous cell cervical cancer results in poorer RFS.

Late Recurrence of Early Stage Cervical Cancer more than 3 Years after Radical Hysterectomy with Pelvic Node Dissection.

BACKGROUND: The aim of this study was to compare the clinicopathological characteristics and outcomes of patients who developed late recurrence (> 3 years) of early stage cervical cancer after radical surgery with those of patients who developed early recurrence (≤ 3 years). We also investigated the risk factors of late recurrence. METHODS: The records of 515 patients with early stage cervical cancer diagnosed between 1999 and 2015 were reviewed. 53 patients developed recurrence, 35 early and 18 late, and their clinicopathological characteristics and outcomes were compared. Of the 515 patients, the records for 307 patients who remained tumor free for at least 3 years after radical surgery were further examined. RESULTS: No significant differences were found in clinicopathological characteristics and clinical outcomes between the early and late recurrence groups with regard to age, stage, histology, tumor size, lymphovascular space invasion, stromal invasion, parametrial involvement, node status, vaginal margin, preoperative blood testing, adjuvant therapy, symptom status at recurrence, site of recurrence and survival after recurrence. Late recurrence was detected in 18 of the 307 patients (5.9%). Only node status and deep stromal invasion (DSI) were independently associated with late recurrence. CONCLUSION: Lymph node metastasis and DSI are risk factors for late recurrence. Careful long-term follow-up is needed, particularly in cases with lymph node metastasis and/or DSI.

The prognostic impact of histological type on clinical outcomes of early-stage cervical cancer patients whom have been treated with radical surgery.

The aim of this study was to determine the prognostic impact of histological type among squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC) on the treatment outcome of early-stage cervical cancer patients after radical hysterectomy. The cohort comprised of 626 patients, diagnosed with stages IA2-IB1 cervical cancer between 1987 and 2013. Four hundred and one patients had SCC, 190 had AC and 35 had ASC. The 5-year disease-free survival (DFS) rates for AC, SCC and ASC were 89.3% (95%CI 83.2-93.2), 88.7% (95%CI 84.8-91.7) and 82.1% (95%CI 61.9-92.2), respectively (p = .594). In multivariate analyses, only older age and deep stromal invasion were statistically significantly associated with DFS, whereas histologic cell type was not (p = .524). Subgroup analysis showed that in the intermediate-high-risk groups, the SCC group had a significantly longer DFS, compared with the AC group or the ASC group (p = .001) while there was no DFS difference in the low-risk group. We believe that histologic cell type had no impact in low-risk early-stage cervical cancer patients. However, in the intermediate-high-risk groups, SCC is a more favourable factor for survival than AC/ASC.

The Effect of Metformin on Oncological Outcomes in Patients With Cervical Cancer With Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to evaluate any association between metformin use and oncological outcomes of cervical cancer in patients with type 2 diabetes mellitus (DM). METHODS: We retrospectively identified 248 patients with cervical cancer with type 2 DM who received primary treatment between 2004 and 2015. The clinicopathological characteristics and oncological outcomes were collected and analyzed. The patients were then separated into metformin use (n = 118) or non-metformin use (n = 130) groups. RESULTS: With a median follow-up of 2.85 years, patients who were given metformin had lower recurrence rate than patients who did not receive metformin (P = 0.011). The 5-year disease-free survival (DFS) and overall survival (OS) were 81.55% and 93.27% in the metformin use group, and 65.06% and 86.82% for the non-metformin use group, respectively. In multivariate analysis, non-metformin use (hazard ratio [HR], 1.89; P = 0.037), baseline hypertension (HR, 2.52; P = 0.005), and stage (HR for stage II vs I, 3.48; HR for stage III vs I, 6.45; P = 0.01) were independent adverse prognostic factors for DFS, whereas the statistically significant independent prognostic factors for OS were age (HR for age >65 vs ≤50, 3.86; P = 0.044) and stage (HR for stage III-IVA vs I-II, 3.45; P = 0.007). CONCLUSIONS: Our findings demonstrate that metformin use is associated with improved DFS, but not in OS in patients with cervical cancer with type 2 DM. Further large-scale and long-term follow-up studies are warranted to confirm the antitumor effects of metformin.

Clinical Aspects and Prognostic Factors for Survival in Patients with Recurrent Cervical Cancer after Radical Hysterectomy.

BACKGROUND: The aim of this study was to investigate the clinical aspects and prognostic factors for survival in patients with recurrent cervical cancer after radical hysterectomy with node dissection (RHND) for stages IA2-IB1. PATIENTS AND METHODS: Clinicopathologic characteristics of the primary tumor, pattern of recurrence, method of detection, salvage treatment, and outcome were reviewed from the medical records of patients who underwent RHND between 1987 and 2015. Prognostic factors were identified using a Cox regression model. RESULTS: Of 702 patients enrolled in the study, 84 (11.9%) had recurrence. 58, 17, and 9 patients had locoregional, distant, and combined recurrence, respectively. No association between clinicopathologic features and recurrence patterns was observed. Most recurrence patients (63.1%) complained of symptoms prior to examination. The majority of asymptomatic recurrence patients (71.4%) were diagnosed by physical and/or pelvic examination. 5-year overall survival after recurrence (SAR) was 34.3%. On multivariate analysis, pattern of recurrence (p = 0.003), symptom status (p = 0.011), age (p = 0.035), and white blood cell (WBC) count (p = 0.017) were independent prognostic factors for overall SAR. CONCLUSION: Only pattern of recurrence, symptom status, age, and WBC count were found to be prognostic factors in recurrent cervical cancer after RHND. Follow-up programs after RHND should be directed toward early detection of recurrence.