Quantitative analysis of heterogeneous tumor enhancement pattern and correlation with outcome in cervical cancer

To investigate the value of blood oxygenation level-dependent (BOLD) MRI as a predictor of clinical outcomes in cervical cancer patients treated with concurrent chemoradiotherapy (CCRT). Enrolled 92 patients with stage IB2-IVB cervical cancer who received CCRT underwent 3-T BOLD MRI before treatment. The R2* value (rate of spin dephasing, s-1) was measured in the tumor. Cox regression analysis was used to evaluate the associations of imaging and clinical parameters with progression-free survival (PFS) and cancer-specific survival (CSS). Inter-reader reliability for the R2* measurements was evaluated using an intraclass correlation coefficient (ICC). Tumor R2* values were significantly different between patients with and without disease progression (p < 0.001). Multivariate analysis demonstrated that tumor R2* value was significantly independent factor for PFS (hazard ratio [HR] = 5.746, p < 0.001) and CSS (HR = 12.878, p = 0.001). Additionally, squamous cell carcinoma antigen (HR = 1.027, p = 0.001) was significantly independent factor for PFS. Inter-reader reliability for the R2* measurements was good (ICC = 0.702). Pretreatment 3-T BOLD MRI may be useful for predicting clinical outcomes in uterine cervical cancer patients treated with CCRT, with good inter-reader reliability. • Tumor R2* values are different between patients with and without disease progression. • The R2* value is an independent factor for treatment outcomes in cervical cancer. • Inter-reader reliability for R2* measurements using BOLD MRI is good.

Background: Cervical cancer remains one of the most prevalent cancers globally and a leading cause of cancer-related deaths among women. Early detection and precise prognostic assessment are vital for enhancing outcomes in cervical cancer patients. The purpose of this study is to evaluate the predictive value of preoperative PLR and serum albumin levels for clinicopathological outcomes in cervical cancer. Aim of the Study: The aim of the study was to evaluate the predictive value of preoperative Platelet-to-Lymphocyte Ratio and Serum Albumin levels on clinicopathological outcomes in patients with cervical cancer. Methods: This cross-sectional study, conducted at the Department of Gynecological Oncology, BSMMU, Dhaka (July 2022–June 2023), analyzed 120 women with early-stage (IA-IIA) cervical cancer to assess the association of PLR, S.Albumin for clinicopathological outcome using SPSS 27.0. Data included socio-demographics, clinical details, and serum markers. Results: The majority of participants were aged 30-44 years (46.7%) and married before 18 years of age (83.3%). Most had a PLR &lt;128.3 (62.2%) and SA ≥3.5 (57.8%). Larger tumors (2-4 cm), higher prevalence of lymphovascular space invasion (LVSI), and deeper stromal invasion (≥½ thickness) were significantly associated with higher PLR (≥128.3) and lower SA (&lt;3.5) (p &lt; 0.001, p = 0.006). Conclusion: Preoperative Platelet-to-Lymphocyte Ratio and Serum Albumin levels can serve as valuable predictors of clinicopathological outcomes in cervical cancer, aiding in personalized treatment strategies.

5025 Background: The ability to predict efficacy prior to or early during the course of a therapeutic modality can lead to improved outcome by avoiding ineffectual therapies. The purpose of this study was to test if in-vivo functional MR imaging can, by reflecting microcirculatory response of tumor to cytotoxic therapy, predict failure early during the course of treatment in cervical cancer. Methods: One-hundred and one patients with cervical cancer stages IB2-IV treated with radiation/chemotherapy (RT/CT) underwent Dynamic Contrast Enhanced (DCE) MRI before (1st MRI) and during RT at 2 weeks (2nd MRI) and 4 weeks of RT (3rdMRI). Mean follow up was 4.9 years (1.5–8.0 years). Pelvic tumor control and disease-free survival were correlated with imaging parameters derived from the time/signal-intensity curve of the DCE-MRI of each tumor pixel. These included the signal intensity (SI) of the plateau phase (SIp), the lowest 2.5th and 5.0th percentiles of the entire tumor pixels (SI 2.5 and SI 5.0), the slope of...

Cervical Cancer Outcomes in Elderly Women Treated with EBRT and Brachytherapy +/- Concurrent Chemotherapy

Cervical cancer is one of the most common malignant tumors among women worldwide, with particularly high incidence and mortality rates in developing countries. Early diagnosis and precise treatment of cervical cancer are critical for improving patient survival and quality of life. Current studies have identified tumor heterogeneity as a key factor influencing therapeutic outcomes in cervical cancer. Although conventional imaging modalities such as two-dimensional ultrasonography, CT, and MRI play important roles in tumor diagnosis and staging, they are limited in their ability to comprehensively reveal tumor heterogeneity. In recent years, the emergence of three-dimensional (3D) ultrasonography has provided a novel approach for precise tumor diagnosis and personalized treatment. Compared with traditional 2D ultrasonography, 3D ultrasonography can more accurately assess tumor morphology, volume, and boundaries, and can effectively distinguish between benign and malignant tumors through dynamic blood flow analysis. Thus, 3D ultrasonography offers clinicians more detailed spatial information about tumors and enables a more comprehensive evaluation of cervical cancer heterogeneity. Moreover, the integration of 3D ultrasonography with other imaging techniques, such as diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced MRI (DCE-MRI), can further enhance the accuracy of early diagnosis, staging, and treatment response monitoring in cervical cancer.

Based on the nearly absolute etiologic link between carcinogenic human papillomavirus (HPV) and cervical cancer, two new approaches for the prevention of cervical cancer have emerged: (1) HPV vaccination for primary HPV prevention in younger women and (2) carcinogenic HPV detection for secondary prevention via identifying and treating cervical precancer and early cancers. Both have demonstrated high degrees of efficacy with maximum effectiveness guided by an understanding of the causal model and application of these technologies in an age appropriate manner.1 Despite the advent of these promising prevention tools, there is a real need to develop nonsurgical methods for treating cervical precancerous lesions and even early cancer for three reasons. First, current HPV vaccines are prophylactic and do not treat pre-existing HPV infections.1 Second, surgical excision of screen-detected precancerous lesions, while a highly efficacious (90–95%) treatment1 increases the risk of preterm delivery and infant morbidity and mortality.2 Third, most women who screen positive by a Pap and/or HPV do not have clinically actionable disease, yet these women are at risk of cervical precancer and cancer in the future and must be followed up intensively. In addition, in the low-resource settings, surgical methods are not commonly available and cryotherapy, while moderately efficacious when its use is limited to smaller lesions, causes significant watery discharge and requires sexual abstinence for several weeks to permit healing of treated epithelium. Despite the knowledge that HPV infection is the obligate cause of cervical cancer, targeted immunological approaches for therapy such as therapeutic vaccines have been unsuccessful.3 Chung and Lambert4 present a novel approach of using estrogen receptor antagonists (selective estrogen receptor modulators or SERMs) to treat cervical precancer and cancer. As noted by the authors, there are strongly supportive laboratory5 and epidemiological data6, 7 that estrogen plays contributing role in cervical carcinogenesis. In this study, Chung and Lambert4 successfully treated 7 E6/E7 transgenic mice that spontaneously manifested cervical cancer with Raloxifene, an estrogen receptor antagonist that reduces the risk of breast cancer. To investigate whether Raloxifene might reduce the incidence of cervical cancer and its immediate precursor, carcinoma in situ (CIS), previously unpublished data on these outcomes from two randomized clinical trials to evaluate two SERMs, tamoxifen and raloxifene, for breast cancer risk reduction were analyzed. The NSABP (National Surgical Adjuvant Breast and Bowel Project), an NCI funded Cooperative Group, has designed and conducted the two large breast cancer prevention trials, Breast Cancer Prevention Trial P-1 (BCPT-P1)8 and Study of Tamoxifen vs. Raloxifene (STAR).9 While both tamoxifen and raloxifene are estrogen receptor antagonists in breast tissue, raloxifene is an estrogen receptor antagonist whereas tamoxifen is an agonist in the human reproductive tract (e.g., Tamoxifen increases the risk of endometrial cancer while raloxifene does not.).4, 10, 11 However, as shown in the Table 1, despite small numbers, there was no evidence that long-term raloxifene use reduces, or long-term tamoxifen use increases, the risk of cervical CIS and cancer (n.b., results were combined because SERMS were reported to treat both in the mouse models, and CIS has a high risk of invading if left untreated12) (BCPT P-1: Placebo vs. Tamoxifen, p = 1.0, two-sided Fisher's exact; STAR: Tamoxifen vs. Raloxifene, p = 1.0, two-sided Fisher's exact). This post-hoc analysis was limited by small numbers. Data from other clinical trials of SERMs13, 14 should be pooled to examine the impact of SERMs on outcomes of cervical precancer and cancer. Until evidence is forthcoming on the positive effects of SERMs on cervical precancer and cancer in humans, extreme caution in interpreting data from mouse models is warranted. Despite the probable role of estrogens in cervical carcinogenesis, the protective effects of SERMs against cervical cancer cannot be inferred based on mouse models. Importantly, the therapeutic effectiveness of SERMs would need to be exceeding high to be acceptable, given the efficacy of current methods of treatment for cervical intraepithelial neoplasia15 and early cervical cancer.16 Dr. Castle acknowledges Dr. Joseph Costantino (University of Pittsburgh, Pittsburgh, PA, USA) for providing data from Breast Cancer Prevention Trial P-1 (BCPT-P1) and the Study of Tamoxifen vs. Raloxifene (STAR). Dr. Castle was supported by the Intramural Research Program of the NIH, National Cancer Institute and he reports no conflicts of interest. Yours sincerely, Philip E. Castle

Background.Despite HPV vaccines’ availability for over a decade, coverage across the US varies. While some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model.Methods.We developed a new mathematical model of HPV transmission and cervical cancer, creating US and state-level models, incorporating country- and state-specific vaccination coverage and cervical cancer incidence and mortality. We quantified the national and state-level impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 on cervical cancer outcomes and the time to elimination defined as <4 per 100k women.Results.Increasing vaccination coverage to 80% in Texas over ten years could reduce cervical cancer incidence by 50.9% (95% credible interval [CrI]:46.6–56.1%) by 2100, from 1.58 (CrI:1.19–2.09) to 0.78 (CrI:0.57–1.02) per 100,000 women. Similarly, New York could see a 27.3% (CrI:23.9–31.5%) reduction, from 1.43 (CrI:0.93–2.07) to 1.04 (Crl:0.66–1.53) per 100,000 women, and California a 24.4% (CrI:20.0–30.0%) reduction, from 1.01 (Crl:0.66–1.44) to 0.76 (Crl:0.50–1.09) per 100,000 women. Achieving 80% coverage in five years will provide slightly larger and sooner reductions. If the vaccination coverage levels in 2019 continue, cervical cancer elimination could occur nationally by 2051 (Crl:2034–2064), but state timelines may vary by decades.Conclusion.Targeting an HPV vaccination coverage of 80% by 2030 will disproportionately benefit states with low coverage and higher cervical cancer incidence. Geographically focused analyses can better inform priorities.

Despite human papillomavirus (HPV) vaccines' availability for over a decade, coverage across the United States varies. Although some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model. We developed a new mathematical model of HPV transmission and cervical cancer, creating national- and state-level models, incorporating country- and state-specific vaccination coverage and cervical cancer incidence and mortality. We quantified the national- and state-level impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 on cervical cancer outcomes and the time to elimination defined as less than 4 per 100 000 women. Increasing vaccination coverage to 80% in Texas over 10 years could reduce cervical cancer incidence by 50.9% (95% credible interval [CrI] = 46.6%-56.1%) by 2100, from 1.58 (CrI = 1.19-2.09) to 0.78 (CrI = 0.57-1.02) per 100 000 women. Similarly, New York could see a 27.3% (CrI = 23.9%-31.5%) reduction from 1.43 (CrI = 0.93-2.07) to 1.04 (CrI = 0.66-1.53) per 100 000 women, and California a 24.4% (CrI = 20.0%-30.0%) reduction from 1.01 (CrI = 0.66-1.44) to 0.76 (CrI = 0.50-1.09) per 100 000 women. Achieving 80% coverage in 5 years will provide slightly larger and sooner reductions. If the vaccination coverage levels in 2019 continue, cervical cancer elimination could occur nationally by 2051 (CrI = 2034-2064), but state timelines may vary by decades. Targeting an HPV vaccination coverage of 80% by 2030 will disproportionately benefit states with low coverage and higher cervical cancer incidence. Geographically focused analyses can better inform priorities.

Human papillomavirus (HPV) DNA sequences are associated with the large majority of invasive cervical carcinoma but the role of specific genotype(s) in the outcome of the disease is still debated. To determine the viral epidemiology in the French population of patients and the prognostic value of HPV genotypes in cervical cancer, we performed a retrospective study in 515 patients treated in our Institution from 1985 to 2005. Ninety-six percent of the cases were found associated with HPV DNA whereas 4% remained HPV negative. High-risk HPV 16/18 genotypes were found in 70% of the cases. HPV 18 was more frequently associated with adenocarcinoma (40.6%) than HPV 16 (10.4%) and found in tumours developed in younger women (mean age, 45.8 years) than HPV 16 (48.3 years) or other HPV types (53.6 years). In multivariate analysis, node involvement (p < 0.0001), parametria invasion (p = 0.009), tumour size (p = 0.01) and HPV status (p = 0.02) were associated with disease-free survival (median follow-up 95 months). Disease outcome was better in tumours associated with intermediate risk HPV types (HPV 31, 33, 35, 39, 52, 53, 58, 59, 73) than in tumours with high oncogenic types (HPV 16, 18, 45) (p = 0.03). Node status and tumour size remained prognostic factor for overall survival. Our data show that HPV genotype is one of the biological factors associated with the outcome of cervical cancer. One third of invasive carcinoma were not associated with HPV 16/18, indicating that the screening for cervical neoplasia should be maintained after prophylactic vaccination against these HPV genotypes.

BackgroundCurrent chemoradiation regimens for locally advanced cervical cancer are fairly uniform despite a profound diversity of treatment response and recurrence patterns. The wide range of treatment responses and prognoses to standardized concurrent chemoradiation highlights the need for a reliable tool to predict treatment outcomes. We investigated pretreatment magnetic resonance (MR) imaging features of primary tumor and involved lymph node for predicting clinical outcome in cervical cancer patients.MethodsWe included 93 node-positive cervical cancer patients treated with definitive chemoradiotherapy at our institution between 2006 and 2017. The median follow-up period was 38 months (range, 5–128). Primary tumor and involved lymph node were manually segmented on axial gadolinium-enhanced T1-weighted images as well as T2-weighted images and saved as 3-dimensional regions of interest (ROI). After the segmentation, imaging features related to histogram, shape, and texture were extracted from each ROI. Using these features, random survival forest (RSF) models were built to predict local control (LC), regional control (RC), distant metastasis-free survival (DMFS), and overall survival (OS) in the training dataset (n = 62). The generated models were then tested in the validation dataset (n = 31).ResultsFor predicting LC, models generated from primary tumor imaging features showed better predictive performance (C-index, 0.72) than those from lymph node features (C-index, 0.62). In contrast, models from lymph nodes showed superior performance for predicting RC, DMFS, and OS compared to models of the primary tumor. According to the 3-year time-dependent receiver operating characteristic analysis of LC, RC, DMFS, and OS prediction, the respective area under the curve values for the predicted risk of the models generated from the training dataset were 0.634, 0.796, 0.733, and 0.749 in the validation dataset.ConclusionsOur results suggest that tumor and lymph node imaging features may play complementary roles for predicting clinical outcomes in node-positive cervical cancer.

Disparities in the management and outcome of cervical cancer in the United States according to health insurance status

IntroductionThree-dimensional image-guided brachytherapy (3D-IGBT) has become widespread, improving the outcomes of cervical cancers dramatically. In 2018, the International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer was...

PurposeThis study was performed to evaluate the outcomes of advanced radiotherapy techniques, including image-guided adaptive brachytherapy (IGABT), in International Federation of Gynecology and Obstetrics (FIGO) stage IVA cervical cancer patients with adjacent organ infiltration. A further aim was to identify prognostic factors influencing overall survival (OS) and local control (LC) in these patients, with a particular focus on toxicity and patient-reported outcomes (PROs).MethodsThis retrospective, single-center study included 31 patients with FIGO stage IVA cervical cancer treated with definitive chemoradiotherapy between 2010 and 2020. All 31 patients underwent external-beam radiotherapy (EBRT), with concurrent cisplatin-based chemotherapy (CTX) administered in 25 cases and additional high-dose-rate brachytherapy (BT) performed in 24 cases. Treatment-related adverse events were categorized in accordance with the Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) [1]. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30), while sexual function was assessed through three specific questions adapted from the EORTC QLQ-BR23 module.ResultsMedian OS was estimated at 51.7 months, with 2‑ and 5‑year OS rates of 58.1 and 46.2%, respectively. Median progression-free survival (PFS) was 48.1 months (95% CI: 0–96.2 months), with 2‑ and 5‑year PFS rates of 52 and 37%. The 10-year LC probability was 70.4%, showing a significant association with improved OS (p = 0.0039). Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.014) and nodal involvement were identified as prognostic factors. The estimated median OS was 108 months for patients treated with BT and 51.7 months for those without. Patients receiving six fractions or a cumulative BT dose of ≥ 24 Gy demonstrated improved 5‑year OS rates of 62.3%, although the difference was not statistically significant. Acute toxicities were reported in 83.9% of patients, primarily grades 1–2, with severe complications such as fistula formation occurring in 16.1%. Late toxicities, predominantly affecting the gastrointestinal and urogenital systems, were observed in 45.2% of patients. Patient-reported outcomes indicated mild to moderate impairments of quality of life, with fatigue and gastrointestinal symptoms being the most frequently reported issues.ConclusionAdvanced radiotherapy, particularly IGABT, achieves durable LC in patients with FIGO stage IVA cervical cancer, supporting its use as a cornerstone of curative-intent treatment. However, systemic progression remains a major challenge, highlighting the need for novel therapeutic strategies, including immunotherapy and liquid biopsy for treatment monitoring. Future prospective trials are essential to validate these findings and refine therapeutic protocols, particularly for high-risk subgroups. Ensuring equitable access to these advanced treatments is critical for improving global outcomes in cervical cancer care.

Modelled estimates for changes in cancer incidence, staging, and demand on health services are presented for a range of potential COVID-related disruptions to national population screening programmes for breast, cervical, and colorectal cancer, indicating markedly different impacts for each programme.

Modelled estimates for changes in cancer incidence, staging, and demand on health services are presented for a range of potential COVID-related disruptions to national population screening programmes for breast, cervical, and colorectal cancer, indicating markedly different impacts for each programme.