Radiation Duration in Women with Cervical Cancer Treated with Primary Chemoradiation: A Population-Based Analysis.
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ABSTRACT:
SUBMITTER: Tergas AI
PROVIDER: S-EPMC4834975 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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Radiation Duration in Women with Cervical Cancer Treated with Primary Chemoradiation: A Population-Based Analysis.
Tergas Ana I AI Neugut Alfred I AI Chen Ling L Burke William M WM Hershman Dawn L DL Wright Jason D JD
Cancer investigation 20160317 3
This study examines factors associated with prolonged radiation duration and its impact on survival in women with cervical cancer treated with primary chemoradiation. Women in the National Cancer Database with stage IB2-IVA cervical cancer from 2003 to 2011 who received radiation and chemotherapy were included. Of 7209 women, who met inclusion criteria, 3401 (47.1%) and 3808 (52.8%) completed radiation in ≤ 8 and > 8 weeks, respectively. There was no overall survival difference for radiation dur ...[more]
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Project description:ObjectivesWe compared clinical performance of three strategies of primary human papillomavirus (HPV) testing, primary cytology and co-testing for cervical cancer screening.DesignA population-based prospective cohort study of clinical performance of screening strategy.SettingPatients recruited from community in Changzhi County, Shanxi Province, China.Patient3209 women aged 30-64 years without gynaecological issues.Primary and secondary outcome measuresThe performance of different screening strategies for detecting cervical intraepithelial neoplasia grade 2 or more severe (CIN2+).ResultsA total of 53 CIN2+ and 31 CIN3+ cases are detected. For CIN2+, sensitivity of primary HPV (95.9%) and co-testing (98.0%) are not statistically different, but significantly higher than primary cytology (48.0%). Specificity (86.8%), colposcopy referral rate (7.8%) and number of colposcopies required to detect one case (9.8) for primary HPV are better than co-testing (79.8%, 11.9%, 14.3%, respectively). For CIN3+, primary HPV, co-testing have 100% of sensitivity and specificity, which is significantly higher than primary cytology (56.7% and 90.2%). Number of colposcopies required to detect one case for primary HPV (15.9) is better than co-testing (23.8).ConclusionsCompared with co-testing, HPV primary screening had comparable sensitivity and higher specificity for CIN2+ detection, and both of them showed better performance than cytology primary screening in cervical cancer screening.
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Project description:Background and purpose:To evaluate longitudinal patient-reported distress in cervical cancer patients treated with definitive chemoradiation (CRT). Materials and methods:Between 2011 and 2016, consenting cervical cancer patients treated with definitive CRT who completed ? 2 revised Edmonton Symptom Assessment System (ESAS-r) questionnaires at clinical visits, including baseline, were included. A linear mixed model was used to assess the longitudinal trend in ESAS-r. A minimal clinically important difference (MCID) for total ESAS-r score was defined as a change of 3-points for improvement and 4-points for deterioration. The proportion of patients with an MCID over time was described using moving averages. To test for changes, mixed effects logistic models were fitted, each of which included patient-specific random intercepts and random slopes. Results:67 patients were eligible for analysis (736 ESAS-r assessments). Median (range) follow-up was 24 months (range: 15-45) and compliance at 12 months was 60% (40/67). There was a significant decrease in ESAS-r scores over time. Baseline ESAS-r was strongly predictive of ESAS-r at follow-up (p < 0.001). The proportion of patients with an MCID for improvement from baseline significantly increased over time (p < 0.001) and the proportion with an MCID for deterioration significantly decreased over time (p < 0.001). No predictors for distress were found. Conclusions:Long-term cervical cancer survivors experience distress that significantly improves over time to an extent expected to be clinically meaningful for patients. Implementing cervical cancer specific patient-reported outcome tools into practice could better inform patient needs.
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Project description:ObjectiveCervical cancer remains the most common cancer among women in sub-Saharan Africa and is also a leading cause of cancer related deaths among these women. The benefit of chemoradiation in comparison with radiation alone for patients with stage IIIB disease has not been evaluated prospectively in women living with human immunodeficiency virus (HIV). We assessed the survival of chemoradiation versus radiation alone among stage IIIB cervical cancer patients based on HIV status.MethodsBetween February 2013 and June 2018, patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIB cervical cancer with or without HIV and treated with chemoradiation or radiation alone, were prospectively enrolled in an observational cohort study. Overall survival was evaluated using the Kaplan-Meier method. Cox proportional hazards modeling was used to analyze associations with survival.ResultsAmong 187 patients, 63% (n=118) of women had co-infection with HIV, and 48% (n=69) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2 year overall survival compared with those receiving radiation alone (59% vs 41%, p<0.01), even among women living with HIV (60% vs 38%, p=0.02). On multivariable Cox regression analysis, including all patients regardless of HIV status, 2 year overall survival was associated with receipt of chemoradiation (hazard ratio (HR) 0.63, p=0.04) and total radiation dose ≥80 Gy (HR 0.57, p=0.02). Among patients who received an adequate radiation dose of ≥80 Gy, adjusted overall survival rates were similar between chemoradiation versus radiation alone groups (HR 1.07; p=0.90). However, patients who received an inadequate radiation dose of <80 Gy, adjusted survival was significantly higher in chemoradiation versus radiation alone group (HR 0.45, p=0.01).ConclusionsAddition of chemotherapy to standard radiation improved overall survival, regardless of HIV status, and is even more essential in women who cannot receive full doses of radiation.
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Project description:BackgroundWe evaluated the relative attribution and interactions of treatment and patient-related risk factors for second primary malignancies (SPMs) in cervical and endometrial cancer survivors.MethodsStage I-III cervical and endometrial cancer survivors' data from the Surveillance, Epidemiology, and End Results (SEER) registry between January 1988 and December 2015 were analyzed. The standardized incidence ratio (SIR), excess absolute risk (EAR), and corresponding 95% confidence interval (95% CI) values were calculated. Analyses were classified based on proxies of human papillomavirus (HPV), smoking, hormone, and radiotherapy (RT) status. Additive and multiplicative interactions were assessed.ResultsCervical cancer survivors had a higher risk for developing potentially HPV and smoking-related SPMs, especially in the RT group (SIRHPV = 3.7, 95% CI: 2.9-4.6; SIRsmoking = 3.2, 95% CI: 2.8-3.6). Second vaginal cancer patients had the highest SIR (23.8, 95% CI: 14.9-36.0). There were strong synergistic interactions between RT and the proxy of smoking (Pinteraction < 0.001), accounting for 36% of potentially smoking-related SPMs in cervical cancer survivors.ConclusionsRT, HPV, and smoking promote SPMs in cervical cancer to different extents. The SPM burden in cervical cancer survivors could be mostly attributed to smoking and RT and their interactions.
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Project description:Background/purposeChemoradiation (CRT) is standard therapy for locally advanced cervical cancer (LACC). However, there is a lack of biomarkers to identify patients at high relapse-risk. We examine metabolic (glucose transporter-1 [Glut-1]), hypoxic (hypoxia inducible factor [HIF-1?]; carbonic anhydrase [CA-9]) and proliferative (Ki-67) markers for prognostic utility in LACC.Materials/methods60 LACC patients treated with CRT had pre-treatment biopsies. Immunohistochemistry was performed for Glut-1, HIF-1a and CA-9, to generate a histoscore from intensity and percentage staining; and Ki-67 scored by percentage of positive cells. For each biomarker, treatment response and survival was compared between low and high-staining groups by logrank testing and multivariate analyses.ResultsHigh Glut-1 expression was associated with inferior progression-free survival (PFS), (hazard ratio [HR] 2.8, p = 0.049) and overall survival (OS), (HR 5.0, p = 0.011) on multifactor analysis adjusting for stage, node positivity, tumour volume and uterine corpus invasion. High Glut-1 correlated with increased risk of distant failure (HR 14.6, p = 0.001) but not local failure. Low Glut-1 was associated with higher complete metabolic response rate on post-therapy positron emission tomography scan (odds ratio 3.4, p = 0.048). Ki-67 was significantly associated with PFS only (HR 1.19 per 10 units increase, p = 0.033). Biomarkers for hypoxia were not associated with outcome.ConclusionsHigh Glut-1 in LACC is associated with poor outcome post CRT. If prospectively validated, Glut-1 may help select patients for more intensive treatment regimens.
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Project description:BackgroundCervical cancer is a major health threat for women. Radiotherapy plays an important role in the treatment of cervical cancer. However, its overall benefit has been questioned due to the risk of second primary malignancies.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to search for cervical cancer patients diagnosed between January 1975 and November 2011. Factors that could possibly affect the occurrence of second primary malignancies included the year of diagnosis, gender, ethnicity, histologic type, SEER cancer stage, histology, grade, and whether surgery, chemotherapy, or radiotherapy were used. Age-adjusted and propensity scoring matching (PSM)-adjusted competing-risk analysis was applied for analysis.ResultsOf the 23,112 patients identified through SEER, 14,800 (64.0%) received radiotherapy. Second malignancies were diagnosed in 2,545 (11.0%) cases. PSM-adjusted competing analysis revealed that patients receiving radiotherapy had a significantly higher risk of developing a second cancer in the colon, rectum and anus [hazard ratio (HR): 1.43; 95% confidence interval (CI): 1.09-1.87; P=0.01], lung and bronchus (HR: 1.41; 95% CI: 1.13-1.76; P=0.002), corpus uteri (HR: 3.71; 95% CI: 1.71-8.06; P<0.001), ovary (HR: 2.79; 95% CI: 1.38-5.64; P=0.004), and urinary bladder (HR: 2.18; 95% CI: 1.35-3.54; P=0.002). However, radiotherapy significantly lowered the risk of second cancers in the female breast (HR: 0.67; 95% CI: 0.52-0.86; P=0.002). Age-adjusted competing-risk analysis showed generally consistent results.ConclusionsRadiotherapy increased the risk of second cancers among cervical cancer patients. Those who underwent radiotherapy had a significantly higher risk of developing a second cancer in the colon, rectum and anus, lung and bronchus, corpus uteri, ovary, and urinary bladder.
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Project description:PurposeA phase I clinical trial (GOG-9929) examined the safety and efficacy of adjuvant immune-modulation therapy with the checkpoint inhibitor ipilimumab [anti-CTL antigen-4 (anti-CTLA-4)] following chemoradiation therapy (CRT) for newly diagnosed node-positive human papillomavirus (HPV)-related cervical cancer. To better understand the mechanism of action and to identify predictive biomarkers, immunologic and viral correlates were assessed before, during, and after treatment.Patients and methodsTwenty-one patients who received CRT and ≥2 doses of ipilimumab and 5 patients who received CRT only were evaluable for translational endpoints. Circulating T-cell subsets were evaluated by multiparameter flow cytometry. Cytokines were evaluated by multiplex ELISA. HPV-specific T cells were evaluated in a subset of patients by IFNγ ELISpot.ResultsExpression of the activation markers ICOS and PD-1 significantly increased on T-cell subsets following CRT and were sustained or increased following ipilimumab treatment. Combined CRT/ipilimumab treatment resulted in a significant expansion of both central and effector memory T-cell populations. Genotype-specific E6/E7-specific T-cell responses increased post-CRT in 1 of 8 HPV16+ patients and in 2 of 3 HPV18+ patients. Elevation in levels of tumor-promoting circulating cytokines (TNFα, IL6, IL8) post-CRT was significantly associated with worse progression-free survival.ConclusionsOur data indicate that CRT alone and combined with ipilimumab immunotherapy show immune-modulating activity in women with locally advanced cervical cancer and may be a promising therapeutic option for the enhancement of antitumor immune cell function after primary CRT for this population at high risk for recurrence and metastasis. Several key immune biomarkers were identified that were associated with clinical response.
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Project description:BackgroundSome young women experience delays in diagnosis of cervical cancer, but little research about ways of studying these delays has been published. A major challenge is that gynaecological symptoms are common in young women, but cervical cancer is rare. This study describes the development and testing of a measure for studying delays in diagnosis in young women with cervical cancer.MethodsProspective development of an interview measure and testing of its ability to reliably and systematically collect relevant data in two large hospitals in London, UK using 27 women aged 18-40 diagnosed with cervical cancer in the previous two years. We developed a semi-structured interview schedule and data extraction form to systematically collect data on symptoms (including nature and duration) and risk factors for delayed diagnosis from young women with cervical cancer. We piloted the measure among young women with cervical cancer (audiorecording it with their permission), refining it iteratively. To complete the measure, we developed a database for managing the data and a manual for using the schedule. Two researchers extracted data from the recorded interviews to assess inter-rater reliability.ResultsThe final interview schedule yielded quantitative data on the nature and duration of symptoms and risk factors for delayed diagnosis. Inter-rater reliability was high. In the pilot, 12 of the 27 women were diagnosed via symptomatic presentation. Median time from the symptom triggering presentation to presentation was one month (interquartile range 0-4 months). Median time from presentation to diagnosis was three months (interquartile range 1-8.5 months).ConclusionsWe have developed a reliable tool for measuring the nature and duration of symptoms in young women with cervical cancer. Pilot data suggest that a substantial proportion of women experience delay between first presentation and diagnosis.
| S-EPMC3835395 | biostudies-literature
Project description:ImportanceThere is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors.ObjectiveTo evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer.Design, setting, and participantsAfter radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018.InterventionsPatients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively.Main outcomes and measuresThe primary end point was the rate of disease-free survival (DFS) at 3 years.ResultsA total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT.Conclusions and relevanceIn this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer.Trial registrationClinicalTrials.gov Identifier: NCT00806117.
| S-EPMC7809615 | biostudies-literature