Identification of prognostic biomarkers for cervical cancer based on programmed cell death-related genes and assessment of their immune profile and response to drug therapy.

BACKGROUND: Programmed cell death (PCD) has been widely investigated in various human diseases. The present study aimed to identify a novel PCD-related genetic signature in cervical squamous cell carcinoma (CESC) to provide clues for survival, immunotherapy and drug sensitization prediction. METHODS: Single-sample gene set enrichment analysis (ssGSEA) was used to quantify the PCD score and assess the distribution of PCD in clinicopathological characteristics in The Cancer Genome Atlas (TCGA)-CESC samples. Then, the ConsensusClusterPlus method was used to identify molecular subtypes in the TCGA-CESC database. Genomic mutation analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment, as well as tumor microenvironment (TME) infiltration analysis, were performed for each molecular subtype group. Finally, a prognostic model by Uni-Cox and least absolute shrinkage and selection operator-Cox analysis was established based on differentially expressed genes from molecular subtypes. ESTIMATE (i.e. Estimation of STromal and Immune cells in MAlignantTumours using Expression data) and ssGSEA were performed to assess the correlation between the model and TME. Drug sensitization prediction was carried out with the oncoPredict package. RESULTS: Preliminary analysis indicated that PCD had a potential association clinical characteristics of the TCGA-CESC cohort, and PCD-related genes mutated in 289 (70.59%) CESC patients. Next, four groups of CESC molecular typing were clustered based on 63 significantly prognostic PCD-related genes. Among four subtypes, C1 group displayed the worst prognosis combined with over expressed PCD genes and enriched cell cycle-related pathways. C4 group exhibited the best prognosis accompanied with high degree of immune infiltration. Finally, a five-gene (SERPINE1, TNF, CA9, CX3CL1 and JAK3) prognostic model was constructed. Patients in the high-risk group displayed unfavorable survival. Immune infiltration analysis found that the low-risk group had significantly higher levels of immune cell infiltration such as T cells, Macrophages_M1, relative to the high-risk group, and were significantly enriched in apoptosis-associated pathways, which predicted a higher level of immunity. Drug sensitivity correlation analysis revealed that the high-risk group was resistant to conventional chemotherapeutic drugs and sensitive to the Food and Drug Administration-approved drugs BI.2536_1086 and SCH772984_1564. CONCLUSIONS: In the present study, we first found that PCD-related gene expression patterns were correlated with clinical features of CESC patients, which predicts the feasibility of subsequent mining of prognostic features based on these genes. The five-PCD-associated-gene prognostic model showed good assessment ability in predicting patient prognosis, immune response and drug-sensitive response, and provided guidance for the elucidation of the mechanism by which PCD affects CESC, as well as for the clinical targeting of drugs.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

Vaccinating women previously treated for human papillomavirus-related cervical precancerous lesions is highly cost-effective in China.

Background: The 2021 Chinese Expert Consensus on the Clinical Application of the Human Papillomavirus (HPV) Vaccine recommended vaccination for women who previously received ablative or excisional treatment for high-grade squamous intraepithelial lesion (HSIL). This study evaluates the cost-effectiveness of HPV vaccination in women previously treated for cervical precancerous lesions. Methods: We used a Markov model to simulate the disease progression of both low- and high-risk HPV subtypes. We followed a cohort of 100,000 women aged 18-45 years who received treatment for cervical precancerous lesions for a lifetime (80 years). We used the Incremental Cost-Effectiveness Ratios (ICER) with a 5% discount rate to measure the cost-effectiveness of nine vaccination strategies, including a combination of HPV bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent vaccine (HPV-9), each with three vaccination doses (one-, two- and three-dose). We conducted one-way sensitivity analysis and probabilistic sensitivity analysis. We followed the CHEERS 2022 guidelines. Results: Compared to the status quo, the nine vaccination strategies would result in $3.057-33.124 million incremental cost and 94-1,211 incremental quality-adjusted life-years (QALYs) in 100,000 women previously treated for cervical precancerous lesions. Three vaccination strategies were identified on the cost-effectiveness frontier. In particular, ICER for one-dose HPV-4 vaccination was US$10,025/QALY compared to the status quo (no vaccination); ICER for two-dose HPV-4 vaccination was US$17,641//QALY gained compared to one-dose HPV-4 vaccination; ICER for three-dose HPV-4 vaccination was US$27,785/QALY gained compared with two-dose HPV-4 vaccination. With a willingness-to-pay of three times gross domestic product per capita (US$37655), three-dose HPV-4 vaccination was the most cost-effective vaccination strategy compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. A probabilistic sensitivity analysis confirmed a 99.1% probability of being cost-effective. If the cost of the HPV-9 is reduced to 50% of the current price, three-dose HPV-9 vaccination would become the most cost-effective strategy. Discussion: Three-dose HPV-4 vaccination is the most cost-effective vaccination strategy for women treated for precancerous cervical lesions in the Chinese setting.

Cemiplimab as Second-Line Therapy for Patients with Recurrent Cervical Cancer: A United States-based Cost-effectiveness Analysis.

INTRODUCTION: The efficacy of cemiplimab in recurrent cervical cancer has been demonstrated in the clinical trial EMPOWER-Cervical 1. However, its high price makes patients and clinicians hesitate to use it. Therefore, we designed a study to evaluate its cost-effectiveness. METHODS: We developed a Markov model based on phase III clinical trials to calculate the cost, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over 20 years with a willingness-to-pay (WTP) threshold of $150,000/QALY. The economic data included were obtained from official US government websites and published literature. Sensitivity analysis was used to determine the uncertainties associated with the model, and a subgroup analysis was performed. RESULTS: Compared with chemotherapy, cemiplimab produced an additional 0.597 QALYs (0.751 LYs), resulting in an ICER of $111,211.471/QALY in the United States. The cost of cemiplimab is the most influential factor in the model. The results of these models were robust in all sensitivity analyses. From the American public payers' perspective, subgroup analysis showed cemiplimab was a cost-effective regimen in patients with squamous cell carcinoma, adenocarcinoma, or programmed cell death ligand 1 (PD-L1) ≥ 1%. CONCLUSION: From the American public payers' perspective, cemiplimab is a cost-effective treatment option for second-line treatment of recurrent cervical cancer. Meanwhile, cemiplimab was a cost-effective treatment for patients with PD-L1 ≥ 1 and all histological types.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy for patients with recurrent or metastatic cervical cancer in China.

OBJECTIVE: To evaluate the cost-effectiveness of adding pembrolizumab to various therapy combinations in patients with recurrent or metastatic cervical cancer from the Chinese perspective. MATERIALS AND METHODS: The clinical data for our model was taken from the KEYNOTE-826 trial. The direct costs and utilities were collected from local price databases or previously published literature. A three-state partitioned survival model was designed to simulate the disease process of patients with recurrent or metastatic cervical cancer. All costs were estimated in US dollars, with an annual RMB exchange rate of $1 to 6.45 Yuan in 2021. The willingness to pay threshold (WTP) was set at US$37,663.26/QALY. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to evaluate the influence of variables on the model parameters. RESULTS: For patients with a programmed death-ligand 1 combined positive score greater than 1,compared to the chemotherapy group, pembrolizumab plus chemotherapy contributed an incremental 1.12 Quality-adjusted Life Years (QALYs) with an incremental cost of US$71,884.42, resulting in an incremental cost-effectiveness ratio (ICER) of US$64,338.19, which is beyond the willingness-to-pay (WTP) threshold of China. According to sensitivity analyses, the ICERs were most sensitive to the utility of progressive disease and the cost of pembrolizumab. However, those parameters had no significant impact on the model's outcomes. CONCLUSIONS: The addition of pembrolizumab to various therapy combinations chemotherapy is exorbitant and may not be cost-effective for patients with recurrent or metastatic cervical cancer in China.

Comparative cost-effectiveness of first-line pembrolizumab plus chemotherapy vs. chemotherapy alone in persistent, recurrent, or metastatic cervical cancer.

Background: Treating persistent, recurrent, or metastatic cervical cancer remains challenging. Although pembrolizumab, combined with chemotherapy and bevacizumab, offers a promising first-line option, its cost-effectiveness within the Chinese healthcare system has not been established. Methods: A partitioned survival model was constructed using patient data from the KEYNOTE-826 trial. Efficacy, safety, and economic data from both trial and real-world practices were utilized to determine the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of the treatment strategies. Comprehensive insights were gained through the sensitivity and subgroup analyses. Results: Over five years, the combination of pembrolizumab, chemotherapy, and bevacizumab offered an additional 1.18 QALYs compared to that provided by standard treatments. This regimen increased the costs by US$ 134,502.57, resulting in an ICER of US$ 114,275.67 per QALY, relative to traditional treatment costs. The ICER for the pembrolizumab regimen was further calibrated to be US$ 52,765.69 per QALY. Both ICER values surpassed China's established willingness-to-pay threshold. Importantly, subgroup analysis revealed enhanced cost-effectiveness in patients presenting with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥10. Conclusion: Introducing pembrolizumab alongside chemotherapy and bevacizumab may not be a cost-effective primary strategy for advanced cervical cancer against current standards. However, for patients with a PD-L1 CPS ≥10, the therapeutic and economic outcomes could be improved by adjusting the pembrolizumab price.

Functional MRI radiomics-based assessment of pelvic bone marrow changes after concurrent chemoradiotherapy for cervical cancer.

OBJECTIVES: To quantify the dose-response relationship of changes in pelvic bone marrow (PBM) functional MR radiomic features (RF) during concurrent chemoradiotherapy (CCRT) for patients with cervical cancer and establish the correlation with hematologic toxicity to provide a basis for PBM sparing. METHODS: A total of 54 cervical cancer patients who received CCRT were studied retrospectively. Patients underwent MRI IDEAL IQ and T2 fat suppression (T2fs) scanning pre- and post-CCRT. The PBM RFs were extracted from each region of interest at dose gradients of 5-10 Gy, 10-15 Gy, 15-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy, and > 50 Gy, and changes in peripheral blood cell (PBC) counts during radiotherapy were assessed. The dose-response relationship of RF changes and their correlation with PBC changes were investigated. RESULTS: White blood cell, neutrophils (ANC) and lymphocyte counts during treatment were decreased by 49.4%, 41.4%, and 76.3%, respectively. Most firstorder features exhibited a significant dose-response relationship, particularly FatFrac IDEAL IQ, which had a maximum dose-response curve slope of 10.09, and WATER IDEAL IQ had a slope of - 7.93. The firstorder-Range in FAT IDEAL IQ and firstorder-10Percentile in T2fs, showed a significant correlation between the changes in ANC counts under the low dose gradient of 5-10 Gy (r = 0.744, -0.654, respectively, p < 0.05). CONCLUSION: Functional MR radiomics can detect microscopic changes in PBM at various dose gradients and provide an objective reference for bone marrow sparing and dose limitation in cervical cancer CCRT.

Assessment of cisplatin-induced nephrotoxicity and its associated factors among cervical cancer patients in the leading tertiary hospital in Kenya.

INTRODUCTION: Cisplatin is the widely used antineoplastic agent in managing cervical cancer despite nephrotoxicity being a major concern. In addition, there was a paucity of data about the degree of nephrotoxicity due to cisplatin in the study setting. Therefore, this study aimed to investigate the prevalence of cisplatin nephrotoxicity among cervical patients. METHODS: A retrospective cross-sectional study was conducted at the Cancer Treatment Centre of Kenyatta National Hospital among 100 cervical cancer patients treated with a cisplatin regimen. Simple random sampling was employed to the recruit medical record of patients. This study used a data abstraction tool to extract the patients' relevant socio-demographic and clinical characteristics. The data were analysed using Statistical Package for Social Sciences version 25.0 software. Frequency tables and figures were used to present the findings of the study. Binary logistic regression analysis was used to determine factors associated with cisplatin nephrotoxicity. RESULTS: The study showed a mean age of 52.09 ± 10.44 years. The prevalence rate of cisplatin-induced nephrotoxicity in cervical cancer patients was 45%. Of these patients, 36% and 9% patients had grade 1 and 2 nephrotoxicities, respectively. Comorbidities (crude odd's ratio (COR) = 3.05, 95% confidence interval [CI] = 1.3-7.02, p = 0.011), hypertension (COR = 3.0, 95% CI = 1.1-7.8, p = 0.03), and more than three cycles of cisplatin treatment (adjusted odd's ratio = 4.5, 95% CI = 1.19-17.0, p = 0.027) were significant factors of nephrotoxicity. CONCLUSION: The prevalence of cisplatin-induced nephrotoxicity among cervical cancer patients was high in the study setting. Comorbidities, number of cycles and types of comorbidities were significant factors associated with cisplatin nephrotoxicity.

Pembrolizumab with or without bevacizumab for recurrent or metastatic cervical cancer: A cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of the addition of pembrolizumab in various combinations in patients with recurrent/metastatic cervical cancer. METHODS: A decision-analysis model evaluated the cost-effectiveness of chemotherapy plus pembrolizumab and bevacizumab (CPB) relative to chemotherapy plus pembrolizumab (CP) and chemotherapy plus bevacizumab (CB) in cervical cancer patients. Data from KEYNOTE-826 was used to estimate quality-adjusted life-years (QALYs). Drug cost estimates were obtained using average wholesale prices. Incremental cost-effectiveness ratios (ICERs) were calculated to determine cost/QALY. The willingness-to-pay threshold (WTP) was set a $100,000/QALY. Sensitivity analyses were performed on cost and effectiveness for pembrolizumab-containing regimens. RESULTS: Cost of treatment with CB, CP, and CPB were $416 million (M), $713 M, and $1.51 billion, respectively. Relative to CB, the ICER for CP was $92,678. CPB was dominated. Sensitivity analyses were performed varying the cost and efficacy of CP and CPB. If overall survival (OS) with CP decreased from 24.4 months to 23.4 months, the ICER would exceed the WTP. If the OS from CP is assumed to be 20.4 months, the ICER increases to $187,746. The ICER for CP improves to $63,670 when the model is restricted to PD-L1 positive cancers. With CP eliminated, CPB becomes cost-effective relative to CB if the cost of pembrolizumab per cycle decreases from $12,080 to $2913 for the baseline model and to $4644 for the PD-L1 model. CONCLUSIONS: CP is cost-effective relative to CB for recurrent or metastatic cervical cancer. The efficacy of CPB would need to far exceed both CB and CP to be cost-effective. Restricting the model to patients with PD-L1 positive tumors dramatically improves the ICER for CP relative to CB by $30,000/QALY.

Cost Effectiveness of Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India-A Model-Based Economic Analysis.

PURPOSE: Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS: Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS: Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION: Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

Treatment patterns and economic burden among cervical and endometrial cancer patients newly initiating systemic therapy.

Aim: To evaluate treatment patterns, healthcare resource use (HCRU) and all-cause healthcare costs among patients with cervical or endometrial cancer newly initiating systemic therapy. Methods: We identified patients with cervical or endometrial cancer newly initiating systemic therapy - a claims-based proxy for advanced disease - between 2014 and 2019, described them by line of therapy (LOT), and summarized the per patient per month (PPPM) HCRU and healthcare costs per LOT. Results: Among 1229 patients with cervical cancer and 2659 patients with endometrial cancer, LOT1 therapies included systemic only (cervical, 50.1%; endometrial, 83.2%) and systemic with radiation therapy (cervical, 49.9%; endometrial, 16.8%). Mean PPPM total costs were: LOT1 (cervical, US$15,892; endometrial, US$11,363), LOT2 (US$20,193; US$14,019) and LOT3+ (US$16,576; US$14,645). Conclusions: Overall, patients received guideline-concordant care and experienced significant economic burden, which increased with LOT.

Trends in treatment patterns and costs of care among patients with advanced stage cervical cancer.

BACKGROUND: Current treatments for recurrent or metastatic cervical cancer (r/mCC) do not offer satisfactory clinical benefits, with most patients progressing beyond first-line (1L) treatment. With new treatments under investigation, understanding current treatment patterns, the impact of newly approved therapies, and total costs of care for r/mCC are important. METHODS: A retrospective analysis of a US commercial insurance claims database to identify adult patients with r/mCC between 2015 and Q1-2020; defining 1L treatment as the first administration of systemic treatment without concomitant chemoradiation or surgery. Patient characteristics, treatment regimens, duration of therapy, and total costs of care were evaluated for each line of therapy. RESULTS: 1323 women initiated 1L treatment for r/mCC (mean age, 56.1 years; mean follow-up, 16.5 months). One-third (n = 438) had evidence of second-line (2L) treatment; of these, 129 (29%) had evidence of third-line (3L) treatment. No regimen represented a majority among 2L+ treatments. The 2018 approval of pembrolizumab led to increased 2L immunotherapy use (0% in 2015, 37% in 2019/Q1-2020). However, only a small proportion of patients stayed on immunotherapy for a prolonged period. Mean per-patient-per-month total costs of care during treatment were $47,387 (1L), $77,661 (2L), and $53,609 (3L), driven primarily by outpatient costs. CONCLUSIONS: No clear standard of care was observed in 2L+. Although immunotherapy is increasingly used in 2L+, only a small subset of patients stayed on immunotherapy for a prolonged period, suggesting a need for more therapeutic options. Better understanding of disease biology and the introduction of new therapies may address these unmet needs.

Cost-effectiveness analysis of pembrolizumab for treatment of US patients with persistent, recurrent, or metastatic cervical cancer.

OBJECTIVE: The effectiveness of pembrolizumab for persistent, recurrent, or metastatic cervical cancer has been demonstrated. We aimed to evaluate its cost-effectiveness from the United States (US) healthcare payers perspective. METHODS: A partitioned survival model over a 30-year lifetime horizon was developed to compare the cost and effectiveness of pembrolizumab versus placebo based on clinical data from the KEYNOTE-826 phase 3 randomized trial. Costs and health state utilities were obtained from literature and publicly available databases. The incremental cost-effectiveness ratio (ICER) was measured. One-way and probabilistic sensitivity analyses were conducted. RESULTS: For the Intention-to-Treat patients, pembrolizumab was associated with an additional 0.74 quality-adjusted life-year (QALY) at an additional cost of $182,271 when compared with placebo. The ICER was $247,663/QALY. For patients with a programmed death-ligand 1 combined positive score ≥ 1 and 10, the ICER was $253,322/QALY and $214,212/QALY, respectively. One-way sensitivity analyses showed that pembrolizumab had the greatest impact on the ICER. Probabilistic sensitivity analyses showed that the probability of pembrolizumab being cost-effective was zero at the current willingness-to-pay threshold of $150,000/QALY. The price of pembrolizumab had to reduce at least to $28.336 (55.8% of the current price) for it to be cost-effective in a 50% of chance. CONCLUSION: The addition of pembrolizumab to chemotherapy is costly and might not be cost-effective for persistent, recurrent, or metastatic cervical cancer at the current price in the US.

Association of gynecologic oncology versus medical oncology specialty with survival, utilization, and spending for treatment of gynecologic cancers.

BACKGROUND: We examined the association of gynecologic oncology (GYO) versus medical oncology (MEDONC) based care with survival, health care utilization and spending outcomes in women undergoing chemotherapy for advanced gynecologic cancers. METHODS: Women with newly diagnosed stage III-IV uterine, ovarian, and cervical cancers from 2000 to 2015 were identified in SEER-Medicare. We assessed the association of provider specialty with overall survival, emergency department utilization, admissions, and spending. Outcomes were assessed using unadjusted and Inverse Treatment Probability Weighted propensity-score applied, multi-variable cox modeling, Poisson regression, and generalized models of log-transformed data. RESULTS: We identified 7930 gynecologic cancer patients (4360 ovarian, 2934 uterine, 643 cervix). 37% were treated by GYO and 63% by MEDONC. For ovarian patients, GYO care was associated with improved OS (median OS 3.3 v. 2.9 years; HR 0.85, 95%CI 0.80, 0.91, p < .0001) and similar mean spending per month ($4015 v. $4316, mean ratio 0.97 (95% CI 0.93, 1.02), p = .19), compared to MEDONC in adjusted analyses. For uterine patients, GYO care was associated with similar OS, but decreased spending ($3573 v. $4081, mean ratio 0.87 (95% CI.81, 0.93), p < .0001), and decreased ED utilization (RR 0.76, 95% CI 0.69, 0.85, p < .0001). For cervical patients, GYO care was associated with similar OS, and similar spending. Admissions were more likely in ovarian (RR 1.23, 95%CI 1.11, 1.37, p = .0001) and cervical patients (RR 1.26, 95% CI 1.05, 1.51, p = .015) treated by GYO, in adjusted analyses. CONCLUSIONS: GYO based care was associated with improved OS and equal spending for patients with advanced stage ovarian cancer. Uterine and cervix patients had similar OS, and less or equal spending respectively, when treated by GYO compared to MEDONC.

Assessment of malnutrition by unintentional weight loss and its implications on oncologic outcomes in patient with locally advanced cervical cancer receiving primary chemoradiation.

OBJECTIVES: To determine the prevalence, risk factors for, and clinical implications of unintentional weight loss on oncologic outcomes in locally advanced cervical cancer (LACC) treated with concurrent chemotherapy and contemporary radiation techniques. METHODS: This a single-institution, retrospective cohort study of patients with LACC who received definitive chemoradiation (CRT) from 2010 to 2015. Clinicopathologic factors were abstracted by chart review and characterized using descriptive statistics. Factors associated with severe weight loss (≥10% from baseline) were determined by Chi-square test. Time-to-event analysis was performed using the Kaplan Meier method and regression was performed using the Cox Proportional hazards model. RESULTS: One hundred and eight patients comprised the cohort. The majority of patients were White, obese, and had squamous histology. Almost 80% of patients experienced at least some weight loss, with 14% of patients experiencing severe weight loss. Patients with FIGO 2009 stage 3 or 4 disease had a 3.4-fold increased risk of severe weight loss compared to those with earlier stage disease. Patients who had severe weight loss had a higher risk for death (HR = 2.37, 95% confidence interval [CI] 1.77, 7.37, p = 0.036) and a trend toward high risk for recurrence (HR = 1.43, 95% CI 0.46, 3.32, p = 0.107) compared to patients without severe weight loss. CONCLUSION: Unintentional weight loss is a common symptom of patients with LACC receiving CRT that affects oncologic outcomes, yet it remains under-recognized. Increased awareness of weight loss and malnutrition may encourage interventions to improve this potentially modifiable risk factor for worse prognosis and quality of life.

CdO nanoparticles, c-MWCNT nanoparticles and CdO nanoparticles/c-MWCNT nanocomposite fibres: in vitro assessment of anti-proliferative and apoptotic studies in HeLa cancer cell line.

A simple ultrasonic assisted chemical technique was used to synthesise cadmium oxide (CdO) nanoparticles (NPs) and CdO NPs/c-Multiwalled carbon nanotube (c-MWCNT) nanocomposite fibres.To confirm the physio-chemico properties and to analyse surface morphology of the obtained nanomaterials X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM) were performed. To evaluate the anti-cancer property of CdO NPs, c-MWCNT NPs and CdO NPs/c-MWCNT nanocomposite fibres, an anti-proliferative assay test (Methylthiazolyl diphenyl- tetrazolium bromide - MTT assay) were performed on HeLa cells which further estimated IC50 value (Least concentration of sample in which nearly 50% of cells remain alive) under in-vitro conditions. On comparison, CdONPs/c-MWCNT based system was found to be superior by achieving 52.3% cell viability with its minimal IC50 value of 31.2 µg/ml. Lastly, the CdO NPs based system was taken up for an apoptotic study using DNA fragmentation assay for estimating its ability to cleave the DNA of the HeLa cells into internucleosomal fragments using the agarose gel electrophoresis method. In conclusion, based on our observations, CdO NPs/c-MWCNT hybrid based system can be further used for the development of efficient drug delivery and therapeutic systems.

Chemotherapy treatments, costs of care, and survival for elderly patients diagnosed with cervical cancer: an observational study.

Objective: To describe chemotherapy treatments, associated health care use and costs, and survival for women diagnosed with cervical cancer in the United States.Methods: This was a retrospective cohort study of patients aged ≥65 years, identified in linked Surveillance, Epidemiology, and End Results (SEER) and Medicare databases. Women with a new primary diagnosis of cervical cancer between January 2007 and December 2013 were followed until December 2014. Systemic chemotherapy treatments, health care visits and costs (2016 USD rates), and survival were determined by the line of therapy.Results: Of 1651 women in the analysis, 810 (49.1%) were diagnosed at stages I or II, 411 (24.9%) at stage III, and 430 (26.0%) at stage IV. A total of 225 (13.6%) women received first-line (1L) systemic chemotherapy. Of those who received 1L chemotherapy, 73 (32.4%) received second-line (2L) chemotherapy, and 29 (12.9%) received third-line (3L) chemotherapy. During 1L and 2L chemotherapies, patients averaged 5.9 and 6.5 health care visits per month, respectively, and incurred total mean health care costs per patient per month of $7098 and $8770, respectively. Median survival from the start of 1L and 2L chemotherapy was 14.0 and 10.4 months, respectively.Conclusion: Elderly patients with advanced cervical cancer had a poor prognosis, with a median survival of 14 months or less, and had no standard of care for 2L therapy. Systemic chemotherapies pose a substantial economic burden in the range of $7000 to $9000 per patient per month. These results highlight the high unmet medical need among elderly patients with cervical cancer.

Declining brachytherapy utilization for cervical cancer patients - Have we reversed the trend?

OBJECTIVE: Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed. METHODS: The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB. RESULTS: Brachytherapy utilization declined during 2008-10 (52.6%) compared to 2004-2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86-1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011-14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16-1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26-1.65) and uninsured patients (OR 1.28, 95% CI 1.03-1.57). Sensitivity analysis using the boost modality variable confirmed these trends. CONCLUSIONS: In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization.

Ultrasonographic assessment of an induration caused by extravasation of a nonvesicant anticancer drug: A case report.

RATIONALE: Induration may occur after an anticancer drug extravasation in patients who recurrently receive chemotherapy because of reduced choice of an appropriate vein for inserting a peripheral intravenous catheter, resulting in catheter placement difficulty. Although induration affects treatment, its size, shape, or hardness remains unclear in the conventional observation method using palpation and inspection. Here, we report our observation results in using ultrasonography to assess the induration that occurred after an anticancer drug extravasation as a new assessment method. PATIENT CONCERNS: A 58-year-old woman with cervical cancer who complained of pain during the administration of a nonvesicant anticancer drug via a peripheral intravenous catheter. The medical staff's examination showed a swollen site; therefore, the catheter was replaced. DIAGNOSIS: Induration occurred on the site after an extravasation. Over 6 months later, pigmentation and induration, which can easily be confirmed through palpation, persisted. INTERVENTIONS: The subcutaneous tissue in the induration site was observed using ultrasonography (B-mode and elastography). OUTCOMES: The subcutaneous tissue might have degenerated the tissues surrounding the vein, making it thinner. Moreover, the hardness of the subcutaneous tissue was approximately 7 times than that of the surrounding tissues. LESSONS: Induration that affects the vein form and its surrounding tissues should be prevented, and ultrasonography is an effective method to objectively observe the site where extravasation occurred.

Significance of the Ki-67 proliferation index in the assessment of the therapeutic response to cisplatin-based chemotherapy in patients with advanced cervical cancer.

OBJECTIVE: The purposes of this study were to examine the therapeutic response of advanced cervical cancer to Ki-67 proliferative index (Ki-67 PI) dependent cisplatin chemotherapy, and to determine Ki-67 PI referential value that is expected to provide a satisfactory therapeutic response of cervical cancer to cisplatin chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 59 patients treated for cervical cancer at Clinic for Oncology, Clinical Center Nis, Serbia. According to the obtained Ki-67 PI values, patients were divided into three groups, and all the patients received the same cytostatic, cisplatin. Therapeutic response to chemotherapy was evaluated in relation to disease progression presence or absence and progression-free survival after a year follow-up since the first chemotherapy. RESULTS: Survival rate increases with an increase of Ki-67 PI by Kaplan-Meier survival analysis, meaning that survival rate is statistically significantly shorter in the group of patients with Ki-67 PI < 40% in comparison to patients from other two groups (p=0.010). Mann-Whitney test confirmed a statistically significant increase in survival rate among the groups of patients formed according to Ki-67 PI (p<0.05). Kaplan-Meier survival analysis confirmed that the mean survival rate in the group of patients with Ki-67 PI values over 60% is statistically significantly longer in comparison to patients with Ki-67 PI values below or equal 60% (p<0.001). CONCLUSIONS: Advanced cervical cancer with a high Ki-67 PI expression responds better to cisplatin-based chemotherapy, thus resulting in a longer survival rate. The values of Ki-67 PI were determined: high Ki-67 PI (≥ 60%), moderate Ki-67 PI (40-60%), and low Ki-67 PI (≤ 40%).