Advanced Stage Cervical Cancer Patients Research Articles

Prevalence and Survival Rate of Advanced Stage Cervical Cancer Patients with Obstructive Uropathy in a Tertiary Hospital

Introduction: This study aims to determine the prevalence and survival rate of advanced cervical cancer patients with obstructive uropathy based on grade of hydronephrosis, type of hydronephrosis, deobstruction action, type of deobstruction, clinical stage, and cancer cell type.Method: This research is a descriptive analytical study with a cross-sectional retrospective approach. Samples were obtained from medical records of patients with stage IIIB, IVA and IVB cervical cancer who were treated at RSUD Dr. Saiful Anwar Malang in 2016–2023. Sampling was carried out using the total sampling method.Result: Of the 171 patients, the majority of patients had stage IIIB cervical cancer (71.9%), moderate (72.5%) and bilateral (90.1%) hydronephrosis were found in the majority of patients. SCC dominated the sample (82.5%) and was followed by ADC (14.6%). Most patients underwent deobstruction (64.3%) with DJ stent insertion being the most common type of deobstruction (84.5%). Patients with stage IVB have a lower survival rate than IIIB and IVA (p>0.05). Patients with SCC had lower survival (3%) than ADC (5%). The average survival rate for the three grades of hydronephrosis was not significantly different (p>0.05). Patients undergoing deobstruction showed a higher survival rate (5%) (p<0.05). DJ stent, PCN, and UCS insertion showed similar survival rates in patients (p>0.05).Conclusion: Stage IIIB cervical cancer, moderate hydronephrosis, bilateral hydronephrosis, and SCC dominated the patients in the study. Patients with stage IVB cervical cancer, SCC, unilateral or severe hydronephrosis have a worse prognosis. The presence of deobstruction indicates a better prognosis and can be performed with PCN, DJ stent insertion, or UCS.

Survival Status and Predictors Among Women with Advanced Stage of Cervical Cancer.

Cervical cancer is one of the leading causes of cancer death in women, even though it is a preventable disease. Most deaths occur in low- and middle-income countries. In addition to early detection and receipt of standard treatments, survivorship is an important component of high quality of care across the cancer continuum. To assess the survival status of advanced-stage cervical cancer patients after cancer treatment has started. A one-year prospective cohort study was employed to assess the survival status of women with advanced stages of cervical cancer. A total of 180 cervical cancer patients were recruited, and the study was conducted from January 10, 2022, to September 20, 2023. Data entry and analysis were done in the SPSS 29 version. Descriptive statistics were used to examine participant characteristics. The Kaplan-Meier procedure and log rank test were used to estimate the duration of survival. Bivariate and multivariate Cox regression analyses were computed for predictor variables with survival status. Patients receiving cancer treatment at FIGO stages IVA and IVB had survived by 56% and 24%, respectively, whereas patients receiving treatment at stages IIB and IIIA had survived by 100%. The estimated mean survival time at one-year follow-up was 5.706 months (95% CI: 3.785-7.627) for patients with FIGO stage IVB, but 11.537 months (95% CI: 11.199-11.887) for those with stages II and III (P < 0.001). Women over 60 years old had a 1.5-fold higher risk of death than those under 60 (HR: 1.482, P = 0.040). The one-year cumulative survival rate among advanced-stage cervical cancer patients was 77%. Major factors associated with survival were age, cancer stage, the presence of anemia, and waiting time for treatment.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

Objectives:To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. Methods:Patients aged 18–70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0–2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). Results:From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. Conclusions:ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

Pengaruh Psikokuratif terhadap Kadar VEGF-c, Kortisol dan Skor HADS Pasien Kanker Serviks Stadium Lanjut

Background: Cancer diagnosis and therapy that causes chronic stress, its progression to depression increase cortisol and VEGF-c levels in advanced cervical cancer patientsObjective: To know the VEGF-c, cortisol and HADS level in advanced stage cervical cancer patients who get Psychocurative intervention Method : An experimental study of pretest – posttest controle group design in outpatient oncology clinic and ward of Doctor Moewardi General Hospital. Thirty subjects with advanced cervical cancer were randomly divided into 15 patients in the intervention group, and 15 in control. Psycho-curative intervention 4 times a month, 1 time a week, 60 minutes duration. Before and after intervention, each subject of the two groups was examined levels of VEGF-c, cortisol and HADS scores. Data obtained were analyzed by independent t test, Mann Whitney, Pair t and Wilcoxon with the 19th version of SPSS for Windows.Result and Discussion: Average VEGF-c levels before intervention 9006.53 ± 2181.49, after intervention 5631.20 ± 2071.55, p &lt;0.001. The mean cortisol level before intervention was 12.29 ± 4.36, after intervention 6.71 ± 3.88, p &lt;0.001. The mean HADS Anxiety score before intervention was 14.13 ± 3.02, after intervention 8.47 ± 3.07, p &lt;0.001. Mean Depression HADS scores before intervention 13.80 ± 3.21, after intervention 7.20 ± 2.70, p &lt;0.001.Conclusion : VEGF-c levels, cortisol, HADS anxiety scores and depression in patients with advanced cervical cancer decline after psychocurative intervention. Keywords : Psychocurative; VEGF-c; Cortisol; HADS; Cervical cancer

The cortisol level, depression anxiety stress score, and quality of life in patient with advance stage cervical cancer after two years of psychorative intervention

Background: Cervical cancer is the second most cancer in women after breast cancer. Emotional stress is the most common comorbid attacking women with advanced-stage cervical cancer, where 13- 40% are depressed which can increase mortality by 39%. Management of cervical cancer has so far focused on standard chemoradiation treatment, but has paid less attention to other aspects such as cognitive, psychological, spiritual and physical. The study aims to determine cortisol levels, Depression Anxiety Stress (DAS) score and quality of life for patients with advanced-stage cervical cancer after two years of psychocurative interventionMethods: The pretest-posttest group design experimental study, continued previous studies, 30 subjects with advanced-stage cervical cancer patients, divided into 15 subjects received standard and psychocurative treatments, the other 15 as controls only received standard therapy. Psychocurative is done independently three times a week for two years based on psychocurative smart books. Home visits are conducted once per week to monitor, motivate the subject to do the psychocurative independently properly and discipline. Cortisol levels, DAS scores and quality of life were measured before and after treatment, the data were analysed by paired t-tests in the SPSS 25 program.Results: One control group subject died before the study was completed. Before and after psychocurative, cortisol levels in the treatment group were 12.29 ± 4.36 and 6.71 ± 3.88 with p&lt;0.05. The Depressive scores were 14.13 ± 3.02 and 8.46 ± 3.07 with p&lt;0.05. The Anxiety scores 12.13 ± 1.64 and 6.73 ± 2.40 with p&lt;0.05. The Stress scores were 14.40 ± 2.64 and 7.27 ± 2.81 with p&lt;0.05. The quality of life score of the physical domain were 55.00 ± 6.54 and 62.67 ± 8.63 with p &lt;0.05. The Psychical domain was 57.00 ± 9.41 and 65.66 ± 8.42 with p &lt;0.05. The Social domain was 33.67 ± 9.15 and 41.67 ± 10.29 with p &lt;0.05. The Environmental domain was 63.00 ± 1.93 and 69.33 ± 7.76 with p &lt;0.05Conclusions: Psychocurative decreases serum cortisol levels, decreases depression, anxiety, and stress scores and improves the quality of life of the physical, psychological, social and environmental domains.

CD4-T Lymphocyte in Cervical Cancer Patients on Pre-and Post-Chemotherapy

Introduction : Cervical cancer is a gynecology cancer with the highest incidence in the Dr.Soetomo Hospital, Surabaya. Neoadjuvant chemotherapy with cisplatin has been used to increase radiosensitivy of cancer cells before radiotherapy done in advanced stage cervical cancer patients. This research aimed to know the differences of CD4-T lymphocyte profile in stage IIIB patient before and after chemotheraphy administration.Methods : This research was done in February-September 2018. Seventeen patients out of 31 stage IIIB cervical cancer patients planned to receive neoadjuvan chemotherapy with cisplatin every 3 weeks for 3 series were checked for the CD4+ T lymphocyte count and percentage. The examinations were done before the first and after the third chemotherapy administration.Results : Mean±SD of the CD4-T lymphocyte count before chemotherapy was 817±314 cells/μL and mean±SD of the CD4-T lymphocyte percentage was 38.96±8.47%. While mean±SD of the CD4-T lymphocyte count after chemotherapy was 881±335 cells/μL and mean±SD of the CD4-T lymphocyte percentage was 39.01±8.50%. There was no significant difference of CD4-T lymphocyte count between before and after chemotherapy (p=0.471). There was also no significant difference of CD4-T lymphocyte percentage between before and after chemotherapy (p=0.866). Both the CD4-T lymphocyte count and percentage tended to increase in postchemotherapy condition.Conclusion : The CD4-T lymphocyte count and percentage were not significantly different between before and after chemotherapy administration in stage IIIB cervical cancer patients. Both the CD4-T lymphocyte count and percentage tended to increase in postchemotherapy condition.

Comparative study to evaluate dosimetric differences in patients of locally advanced carcinoma cervix undergoing intracavitary brachytherapy under two different anaesthesia techniques: an audit from a tertiary cancer centre in India

BackgroundCarcinoma cervix is amongst the leading causes of mortality and morbidity in women population worldwide. High-dose-rate intracavitary brachytherapy (HDR-ICBT) post external beam radiation therapy (EBRT) is the standard of care in managing locally advanced stage cervical cancer patients. HDR-ICBT is generally performed under general anaesthesia (GA) in operation theatre (OT), but due to logistic reasons, sometimes, it becomes difficult to accommodate all patients under GA. Since prolonged overall treatment time (OTT) makes the results inferior, taking patients in day care setup under procedural sedation (PS) can be an effective alternative. In this audit, we tried to retrospectively analyse the dosimetric difference, if any, in patients who underwent ICBT at our centre, under either GA in OT or PS in day care.ResultsThirty five patients were analysed 16/35 (45.71%) patients underwent HDR-ICBT under GA while 19/35 (54.28%) patients under PS. In both groups, a statistically significant difference was observed between the dose received by 0.1 cc as well as 2 cc of rectum (p < 0.05), while the bladder and sigmoid colon had comparable dosages.ConclusionThough our dosimetric analysis highlighted better rectal sparing in patients undergoing HDR-ICBT under GA when compared to patients under PS, PS can still be considered an effective alternative, especially in centres dealing with significant patient load. Further studies are required for firm conclusion.

246P - The main of reasons of advanced stage cervical cancer in Uzbekistan

BackgroundTo study the main causes of neglect of advanced cervical cancer (CC) in Uzbekistan based on the results of a survey of advanced stage cervical cancer patients. The questionnaire was analyzed in 3 directions: “patient delay”, “doctor delay”, “delay of treatment”. Methods200 patients with advanced cervical cancer were included in the analysis, including: IIA-B stage-17%; IIIA-B stage 80%; IVA stage - 3%. Descriptive analyses were provided with the WHO questionnaire, adopted for local use, which should explore the possible barriers of early detection of cervical cancer. ResultsIn the questionnaire analysis, the following results were obtained in the direction of “doctor delay”: 1. Which doctor did you talk about the symptoms of the disease? General practioner - 8%, gynecologist - 90%, private doctor - 2%; 2. Prior to the establishment of diagnosis contacted doctor: once - 22%, twice - 29%, 3 times and more - 49%. 3. How many times did you have a doctor before starting chemotherapy: Never - 86%, 3 or more times 14%. 4. Some aspects of the treatment surprised patients, no one warned: yes-56%, no-54%; I can easily ask doctor about the disease: Yes-45%, no-55%. 5. Appeal to the doctors before the establishment of diagnosis: twice - 29%, 3 and more time - 49%; To which specialist did you first tell about the symptoms of the disease: Physician - 97%, nurse - 2%, healer - 1%. 6. How many times have been in doctor with relatives: Never -37%; once - 19%; twice - 24%; 3 and more times - 20%. 7. Where you underwent the necessary examinations: State clinic - 70%; private clinic - 30%. ConclusionsThe main reasons for the neglect of cervical cancer in the direction of “doctor delay” are: Weak awareness of general practitioners; Unsatisfactory in forming patients about the severity of the disease, inability to enter the patient's trust; Absence or low level of psychological support of patients; Problems of timely referral of patients to an oncologist; Problems of deontology in the chain: doctor-diagnosis-patient. Elimination of the above-mentioned main causes will lower the incidence and mortality from cervical cancer and improve treatment outcomes, preventing disability of women. Legal entity responsible for the studyNargiza Zakhirova. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The Influence of Psychocurative on Cortisol Level, Anxiety, and Quality of Life in Advanced Stage Cervical Cancer Patients

Every year, there are 500.000 new cases and more than 250.000 deaths caused by cervical cancerworldwide. Cervical cancer patients faced physical and psychological problems several times that it activate stress mechanism such as hypothalamus-pituitary-adrenal (HPA) axis. These recurrent activations caused HPA axis disruption and adverse clinical effects. Several symptoms of endocrine stress response are the change of circadian cortisol rhythm. Cortisol is known as a stress hormone that involves an organism's response to stress and anxiety that influence the quality of life. This research aims to analyze the differences among serum cortisol level, anxiety, and quality of life in cervical cancer patients before and after psychocurative intervention in obstetrics and gynecology wards and polyclinic in RSUD Dr. Moewardi Surakarta. This research is an experimental double-blind randomized controlled clinical trial pre-test post-test group design study. The subjects were advance stage (IIB-IV)cervical cancer patients. The subjects were randomly chosen into fifteen subjects that given standard therapy and psychocurative, while the other fifteen subjects as a control only got standard therapy. Data were obtained from measurement of serum cortisol level, anxiety questionnaire DASS 42 and WHO quality of life questionnaire. Data were analyzed using SPSS 21 using difference test. The difference mean test result of cortisol serum level, anxiety, quality of life from the controlled group and uncontrolled group showed a significant difference (p &lt; 0.05). In conclusion, psychocurative is significant to reduce cortisol level, anxiety, and improve the quality of life in advanced stage cervical cancer patients.

MicroRNA-944 overexpression is a biomarker for poor prognosis of advanced cervical cancer

BackgroundOne-third of cervical cancer patients are still diagnosed at advanced stages. The five-year survival rate is decreased in about 50% of advanced stage cervical cancer patients worldwide, and the clinical outcomes are remarkably varied and difficult to predict. One of the miRNAs known to be associated with cancer tumorigenesis is miR-944. However, the prognostic value of miR-944 in cervical cancer has not been fully investigated. The aim of this study was to analyze clinical significance and prognostic value of miR-944 in cervical cancer.MethodsThe expression levels of miR-944 were detected using quantitative reverse transcription polymerase chain reaction in five types of cervical cancer cell lines and 116 formalin-fixed paraffin-embedded (FFPE) cervical tissues. The association between the expression levels of miR-944 and prognostic value was analyzed using the Kaplan-Meier analysis and Cox proportional hazards model.ResultsThe expression levels of miR-944 in cervical cancer tissues were significantly higher compared with those in normal tissues (P < 0.0001). Moreover, the expression levels of miR-944 in cervical cancer cell lines and FFPE tissues with human papillomavirus (HPV) infection were significantly higher compared to those without HPV infection (P < 0.01 and P = 0.02). High miR-944 expression was also markedly associated with bulky tumor size (P = 0.026), advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.042), and lymph node metastasis (P = 0.030). In particular, high miR-944 expression group showed shorter overall survival than the low miR-944 expression group in the advanced FIGO stage (84.4% vs. 44.4%, HR = 4.0, and P = 0.01).ConclusionsThese results suggest that miR-944 may be used as a novel biomarker for improving prognosis and as a potential therapeutic target.

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

ObjectiveTo 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.MethodsPatients 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).ResultsData 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.ConclusionsACT 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 RegistrationClinicalTrials.gov Identifier: NCT02036164Thai Clinical Trials Registry Identifier: TCTR 20140106001

Abstract 4751: Correlating the genomic and transcriptomic profiles of pre-treatment cervical tumor biopsies with patient recurrence after definitive chemoradiation

Abstract Purpose: The purpose of this study was to identify genomic mutations that correlate with patient recurrence after curative intent chemoradiation therapy in advanced stage cervical cancer patients. Methods: Pre-treatment cervical tumor biopsies and normal blood were prospectively collected from patients treated at Washington University in St. Louis. DNA and RNA was isolated from the fresh frozen tumor biopsies and sent for next-generation sequencing and RNAseq respectively. Targeted exome sequencing was done using a panel of 127 known cancer associated genes, and an additional 8 genes previously reported to be mutated in cervical cancer. Gene tiling was done to probe for 30 different HPV subtypes. Results: The mutational signatures of single nucleotide polymorphisms were an APOBEC cytidine deaminase and CpG site cytidine deamination mutagenesis pattern. The non-silent somatic mutations were analyzed by online prediction algorithms to assess the mutation’s putative effect on protein function. Univariate COX regression was used to correlate patient recurrence with non-silent putatively functional mutations. In our patient cohort 88% of samples were HPV positive, with 74% being the high-risk HPV 16 and 18 subtypes. Patient’s with HPV positive tumors had increased progression-free survival when compared to the HPV negative patient tumors; and the HPV positive patients with HPV 16 had increased progression-free survival over the other HPV subtypes. Complete gene tiling of the HPV 16 and 18 subtypes allowed us to determine whether the HPV DNA was integrated in the host genome or retained episomally. In our patient cohort less than 30% of samples had integrated HPV DNA, and there was no significant difference in progression-free survival between patients with integrated or episomal HPV. Conclusions: The genomic analysis of our advanced staged cervical cancer patient cohort found that epigenetic modifiers were frequently mutated and that cytidine deamination mutagenesis was primarily responsible for the generation of the SNP mutations. Our study identified NSD1 mutations as being correlated with tumor recurrence, indicating that histone modifications and chromatin structure may play an important role in tumor response to ionizing radiation therapy. Gene expression analysis is currently ongoing. Citation Format: Fiona J. Ruiz, Julie K. Schwarz. Correlating the genomic and transcriptomic profiles of pre-treatment cervical tumor biopsies with patient recurrence after definitive chemoradiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4751. doi:10.1158/1538-7445.AM2017-4751

A short time interval between radiotherapy and hyperthermia reduces in-field recurrence and mortality in women with advanced cervical cancer

BackgroundCombined radiotherapy and hyperthermia is a well-established alternative to chemoradiotherapy for advanced stage cervical cancer patients with a contraindication for chemotherapy. Pre-clinical evidence suggests that the radiosensitizing effect of hyperthermia decreases substantially for time intervals between radiotherapy and hyperthermia as short as 1–2 h, but clinical evidence is limited. The purpose of this study is to determine the effect of the time interval between external beam radiotherapy (EBRT) and same-day hyperthermia on in-field recurrence rate, overall survival and late toxicity in women with advanced stage cervical cancer.MethodsPatients with advanced stage cervical cancer who underwent a full-course of curative daily EBRT and (4–5) weekly hyperthermia sessions between 1999 and 2014 were included for retrospective analysis. The mean time interval between EBRT fractions and same-day hyperthermia was calculated for each patient; the median thereof was used to divide the cohort in a ‘short’ and ‘long’ time-interval group. Kaplan-Meier analysis and stepwise Cox regression were used to compare the in-field recurrence and overall survival. Finally, high-grade (≥3) late toxicity was compared across time-interval groups. DNA repair suppression is an important hyperthermia mechanism, DNA damage repair kinetics were therefore studied in patient biopsies to support clinical findings.ResultsIncluded were 58 patients. The 3-year in field recurrence rate was 18% and 53% in the short (≤79.2 min) and long (>79.2 min) time-interval group, respectively (p = 0.021); the 5-year overall survival was 52% and 17% respectively (p = 0.015). Differences between time-interval groups remained significant for both in-field recurrence (HR = 7.7, p = 0.007) and overall survival (HR = 2.3, p = 0.012) in multivariable Cox regression. No difference in toxicity was observed (p = 1.00), with only 6 and 5 events in the short and long group, respectively. The majority of DNA damage was repaired within 2 h, potentially explaining a reduced effectiveness of hyperthermia for long time intervals.ConclusionsA short time interval between EBRT and hyperthermia is associated with a lower risk of in-field recurrence and a better overall survival. There was no evidence for difference in late toxicity.

Effect of Smoking on Advanced Stage Cervical Cancer Patient Survival

Objective: The researchers aim to investigate the relationship between&#x0D; smoking habit and other factors as prognostic factors of cervical&#x0D; cancer.&#x0D; Method: We performed a retrospective and prospective cohort study&#x0D; with subjects that are stage IIB-IVB cervical cancer patients in Dr.&#x0D; Cipto Mangunkusumo Hospital followed up from August 2009 to&#x0D; April 2014. The subjects’medical records were reviewed, and patients&#x0D; were interviewed about their current condition by telephone. Questions&#x0D; asked include smoking habit, spouse’s smoking habit, and mortality&#x0D; status. Patients that could not be contacted by phone were excluded&#x0D; from the study. Statistical analysis was done using Stata 10.&#x0D; Result: Out of 390 cervical cancer patients stage IIB-IVB in 2009,&#x0D; there were 270 patients (69.2%) that were included in the inclusion&#x0D; criteria. Most of the patients are 40-59 years old (82.2%) and are nonsmokers&#x0D; (91.8%). The most frequent clinicopathological characteristic&#x0D; is IIIB (63.3%) and squamous cell carcinoma (71.9%). The 5-&#x0D; year survival rate is 22.6%. There is no statistical significance between&#x0D; advanced stage cervical cancer survival with the patients’ or patients’&#x0D; husbands’ smoking habit.&#x0D; Conclusion: In our study, smoking habits do not aggravate survival&#x0D; rate of advanced stage cervical cancer patients but further research&#x0D; must be done with more sample. Stage, and tumor size both by physical&#x0D; examination and ultrasound can be used as the prognostic factor.&#x0D; [Indones J Obstet Gynecol 2015; 3: 170-176]&#x0D; Keywords: Brigmann Index, cervical cancer, smoking, survival

Effect of p53 codon 72 polymorphism on the survival outcome in advanced stage cervical cancer patients in India.

Background & objectives:The Arg>Pro polymorphism in codon 72 of p53 gene is known to affect the susceptibility of cervical cancer differently in different population worldwide although information regarding its role in determining survival status and disease outcome in patients is lacking. The present study was conducted to determine the genotype frequency and prognostic role of p53 codon 72 Arg>Pro polymorphism in patients with advanced stage cervical cancer in India.Methods:The p53 codon 72 polymorphism was determined in tumour biopsies (n = 107) and matched blood samples (n = 19) in cervical cancer patients using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Effect of p53 genotype on the overall survival (OS) and recurrence-free survival (RFS) was analyzed. Individual Arg or Pro alleles were studied for their significance on survival as Pro carriers (Pro/Pro + Arg/Pro) versus Arg/Arg individuals or Arg carriers (Arg/Arg + Arg/Pro) versus Pro/Pro individuals.Results:The frequencies for Arg/Arg, Arg/Pro and Pro/Pro genotypes were 27.2, 49.5 and 23.3 per cent, respectively. There was no significant difference in the genotypes with respect to patients’ OS or RFS.Interpretation & conclusions:The findings of our study indicated that p53 codon 72 polymorphism might not be an independent marker in predicting clinical outcome in advanced stage cervical cancer patients. Further studies need to be done in larger samples to confirm these findings.

Breaking the DNA damage response to improve cervical cancer treatment.

Every year, cervical cancer affects ∼500,000 women worldwide, and ∼275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%. One of the factors thought to contribute to treatment failure is the ability of tumor cells to repair chemoradiotherapy-induced DNA damage. Therefore, sensitization of tumor cells for chemoradiotherapy via inhibition of the DNA damage response (DDR) as a novel strategy to improve therapy effect, is currently studied pre-clinically as well as in the clinic. Almost invariably, cervical carcinogenesis involves infection with the human papillomavirus (HPV), which inactivates part of the DNA damage response. This HPV-mediated partial inactivation of the DDR presents therapeutic targeting of the residual DDR as an interesting approach to achieve chemoradio-sensitization for cervical cancer. How the DDR can be most efficiently targeted, however, remains unclear. The fact that cisplatin and radiotherapy activate multiple signaling axes within the DDR further complicates a rational choice of therapeutic targets within the DDR. In this review, we provide an overview of the current preclinical and clinical knowledge about targeting the DDR in cervical cancer.

253: Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

253: Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients.

BackgroundTelomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as “mitotic clock” of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy.Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test.ResultsBoth five year overall- and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close ( 58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04).ConclusionsOur results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort.

Conflit ostéoméniscal. Intérêt de sa sémiologie IRM dans le diagnostic d’une lésion méniscale instable

The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in ≥50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1α). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

Abstract 4171: The role of ATM and 53BP1 as predictive markers and therapeutic targets in advanced stage cervical cancer

Abstract Chemoradiation is the standard of care for advanced stage cervical cancer patients and induces cytotoxicity by inducing high levels of DNA breaks in the tumor. The ability of tumor cells to repair therapy-induced DNA damage may counteract the effects of chemoradiation. The pathway responsible for DNA double strand break repair is called the ‘DNA damage response’. In vitro we observed robust radiation-induced G1 and G2 cell cycle arrests in cervical cancer cell lines, despite the expression of HPV oncogenes, which impact the DNA damage response through rapid p53 degradation. Moreover, the DNA damage checkpoint protein ATM and its substrate 53BP1 are required for proper induction of cell cycle checkpoint arrests. Yet, when long-term survival effects were measured, inhibition of ATM, but not 53BP1, strongly sensitized cervical cancer cells to irradiation. To validate the putative role of ATM and 53BP1 in advanced stage cervical cancer we investigated presence and activity of ATM as well as 53BP1 in relation to response-to-treatment in a large, well documented, series of advanced stage cervical cancer patients (n=375). We found that high levels of ATM were related to poor response to chemoradiation (P=0.013). Importantly, high phosho-ATM immunostaining, reflecting active ATM, predicted poor responses to chemoradiation even better (P=0.004). In addition, high phospho-ATM levels predicted shorter disease-specific survival (P=0.020). Although presence of phosphorylated 53BP1 did relate to phospho-ATM (P=0.001), it was not significantly related to any clinicopathological features or survival. Combined, our data suggest the prognostic value of ATM signaling for responses to chemoradiation and point at ATM inhibition as a potential therapeutic target to increase treatment efficacy in advanced stage cervical cancers. Acknowledgements This research is supported by the Dutch Cancer Society (RUG 2007-3719) and the Netherlands Organization for Scientific Research (NWO-VENI 916.76.062). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4171. doi:10.1158/1538-7445.AM2011-4171