Locally Advanced Cervical Cancer Research Articles

A Retrospective Study of Chemotherapy and 3D-Image-Guided Afterloading Intracavitary Radiotherapy in Locally Advanced Cervical Cancer.

Aim To investigate the value of neoadjuvant chemotherapy combined with 3D-image-guided afterloading intracavitary radiotherapy in locally advanced cervical cancer (LACC). Methods Patients with cervical cancer admitted to our hospital from January 1, 2020 to January 1, 2021 were retrieved and analyzed. Cases treated with neoadjuvant chemotherapy and 3D-image-guided afterloading intracavitary radiotherapy were assigned into the observation group (OG), while cases with neoadjuvant chemotherapy alone were assigned into the control group (CG). The short-term effects were determined by RECIST 1.1. Total effective rate (TR) = complete remission (CR) + partial remission (PR). The serum levels of squamous epithelial cell carcinoma antigen (SCC-Ag), glycoantigen 125 (CA125), carcinoembryonic antigen (CEA), and vascular endothelial growth factor (VEGF) were assessed. In view of the difference between tumor markers and diameters before and after treatment, the correlation between them was analyzed by Pearson test. The adverse events were compared, and the amount of operative bleeding and operation time were evaluated. Cox regression analysis was conducted to assess the influencing factors of 1-year disease-free survival time. Results Sixty-seven patients were retrieved, including 30 cases in the OG and 37 cases in the CG. There were no significant differences in age, pathological type, tumor size, FIGO stage, past medical history, or smoking history between the two groups (P > 0.05). The TR of patients in the OG was higher than that in the CG (P < 0.05). The SCC-Ag, CA125, CEA, and VEGF levels in the OG decreased markedly after treatment (P < 0.001). The difference in SCC-Ag, CA125, CEA, and VEGF was positively correlated with the difference in tumor diameter before and after treatment (P < 0.05). The incidence of adverse events revealed no obvious difference between the OG and CG (P > 0.05). Cox regression analysis showed that FIGO stage and treatment regimens were independent prognostic factors for 1-year disease-free survival (P < 0.05). Conclusion Neoadjuvant chemotherapy combined with 3D-image-guided afterloading intracavitary radiotherapy can improve the TR rate and 1-year disease-free survival of LACC patients without increasing the incidence of adverse events.

Risk of recurrence after chemoradiotherapy identified by multimodal MRI and 18F-FDG-PET/CT in locally advanced cervical cancer

Background and purposeMRI, applying dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) sequences, and 18F-fluorodeoxyglucose (18F-FDG) PET/CT provide information about tumor aggressiveness that is unexploited in treatment of locally advanced cervical cancer (LACC). We investigated the potential of a multimodal combination of imaging parameters for classifying patients according to their risk of recurrence. Materials and methodsEighty-two LACC patients with diagnostic MRI and FDG-PET/CT, treated with chemoradiotherapy, were collected. Thirty-eight patients with MRI only were included for validation of MRI results. Endpoints were survival (disease-free, cancer-specific, overall) and tumor control (local, locoregional, distant). Ktrans, reflecting vascular function, apparent diffusion coefficient (ADC), reflecting cellularity, and standardized uptake value (SUV), reflecting glucose uptake, were extracted from DCE-MR, DW-MR and FDG-PET images, respectively. By applying an oxygen consumption and supply-based method, ADC and Ktrans parametric maps were voxel-wise combined into hypoxia images that were used to determine hypoxic fraction (HF). ResultsHF showed a stronger association with outcome than the single modality parameters. This association was confirmed in the validation cohort. Low HF identified low-risk patients with 95% precision. Based on the 50th SUV-percentile (SUV50), patients with high HF were divided into an intermediate- and high-risk group with high and low SUV50, respectively. This defined a multimodality biomarker, HF/SUV50. HF/SUV50 increased the precision of detecting high-risk patients from 41% (HF alone) to 57% and showed prognostic significance in multivariable analysis for all endpoints. ConclusionMultimodal combination of MR- and FDG-PET/CT-images improves classification of LACC patients compared to single modality images and clinical factors.

Treatment planning computed tomography radiomics for predicting treatment outcomes and haematological toxicities in locally advanced cervical cancer treated with radiotherapy: A retrospective cohort study.

We evaluated whether radiomic features extracted from planning computed tomography (CT) scans predict clinical end points in patients with locally advanced cervical cancer (LACC) undergoing intensity-modulated radiation therapy and brachytherapy. A retrospective cohort study. Xiangya Hospital of Central South University, Changsha, Hunan, China. Two hundred and fifty-seven LACC patients who were treated with intensity-modulated radiotherapy from 2014 to 2017. Patients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume, pelvis and sacral vertebrae. The sequentially backward elimination support vector machine algorithm was used for feature selection and end point prediction. Clinical end points include tumour complete response (CR), 5-year overall survival (OS), anaemia, and leucopenia. A combination of ten clinicopathological parameters and 34 radiomic features performed best for predicting CR (validation balanced accuracy: 80.8%). The validation balanced accuracy of 54 radiomic features was 85.8% for OS, and their scores can stratify patients into the low-risk and high-risk groups (5-year OS: 95.5% versus 36.4%, p < 0.001). The clinical and radiomic models were also predictive of anaemia and leucopenia (validation balanced accuracies: 71.0% and 69.9%). This study demonstrated that combining clinicopathological parameters with CT-based radiomics may have value for predicting clinical end points in LACC. If validated, this model may guide therapeutic strategy to optimise the effectiveness and minimise toxicity or treatment for LACC.

560P Neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced cervical cancer (NACI): A prospective, single-arm, phase II trial

Neoadjuvant chemotherapy (NACT) is an emerging approach for locally advanced cervical cancer (LACC), while two-thirds of patients (pts) respond to it and pts without response benefit little. PD-1 inhibitors have exhibited promising role in recurrent or metastatic cervical cancer. Additionally, preclinical evidence for the activation and synergistic effects of NACT on PD-1 inhibitors supports the superiority of neoadjuvant immunotherapy. We designed this phase II study to evaluated the efficacy and safety of preoperative PD-1 inhibitor camrelizumab combined chemotherapy in pts with LACC.

Nomograms Combining Clinical and Imaging Parameters to Predict Recurrence and Disease-free Survival After Concurrent Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer

To investigate the value of nomograms based on clinical prognostic factors (CPF), intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and MRI-derived radiomics in predicting recurrence and disease-free survival (DFS) after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Retrospective analysis of data from 115 patients with ⅠB-ⅣA cervical cancer who underwent CCRT and had been followed up consistently. All patients were randomized 2:1 into training and validation groups. Pre-treatment IVIM-DWI parameters (ADC-value, D-value, D*-value and f-value) and pre- and post-treatment three-dimensional radiomics parameters (from axial T2WI) of primary lesions were measured. The LASSO algorithm and Logistic regression analysis were used to filter texture features and calculate radiomics score (Rad-score). Multivariate Logistic and Cox regression analysis was used to construct nomograms to predict recurrence and DFS for patients with LACC after CCRT respectively, with internal and external validation. External beam radiotherapy dose, f-value, pre-treatment and post-treatment Rad-score were independent prognostic factors for recurrence and DFS in patients with cervical cancer, forming Model1 and Model2, with OR values of 0.480, 1.318, 3.071, 3.200 and HR values of 0.322, 3.372, 5.138, 7.204. The area under the curve (AUC) of Model1 for predicting recurrence of cervical cancer was 0.977, with internal and external validation C-indexes of 0.977 and 0.962. The AUC for Model2 predicting disease-free survival (DFS) at 1, 3, and 5 years was 0.895, 0.888 and 0.916 respectively, with internal and external C-indexes of 0.860 and 0.892. The decision curves analysis and clinical impact curves further indicate the high predictive efficiency and stability of nomograms. The nomograms based on clinical, IVIM-DWI and radiomics parameters have high clinical value in predicting recurrence and DFS of patients with LACC after CCRT and can provide a reference for prognostic assessment and individualized treatment of cervical cancer patients.

The value of the SUV ratio between lymph node and bone marrow in predicting pelvic lymphatic metastasis of patients with locally advanced cervical cancer: an integrated PET/CT study.

PurposeThis study aimed to evaluate the value of the standardized uptake value (SUV) ratio between lymph nodes and bone marrow (BM) measured by Fluorine-18-fluorodeoxyglucose PET and computed tomography (18F-FDG PET/CT) for predicting pelvic lymph node (PLN) metastasis in patients with locally advanced cervical cancer (LACC).Materials and methodsA total of 62 patients with pathological stage Ib-IVa cervical cancer who underwent 18F-FDG PET/CT before treatment were reviewed retrospectively. We measured the metabolic and morphological parameters of lymph nodes and primary tumors, bone marrow SUV (SUVBM) and calculated the ratio of lymph nodes maximum SUV (SUVmax) to bone marrow SUV (SUVLN/BM) and the ratio of short-axis diameter to long-axis diameter (Ds/l) of lymph nodes. A receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic efficacy of each parameter.ResultsThere were 180 lymph nodes with pathological evidence included in the study. Our results indicated that Ds/l, SUVmax of lymph nodes (SUVLN) and SUVLN/BM were independent risk factors for PLN metastasis in LACC (P < 0.05), and SUVLN/BM showed the best diagnostic performance by ROC curve analysis. The SUVBM in the anemia group was significantly higher than that in the nonanemia group (3.05 vs. 2.40, P < 0.05); furthermore, false-positive cases decreased when the SUVLN/BM was used as the diagnostic criterion instead of SUVLN, especially in the anemia group. ROC curve analysis showed that the area under the curve value of the combination of SUVLN/BM and Ds/l was 0.884 (P < 0.05), which was higher than Ds/l or SUVLN/BM alone.ConclusionsSUVLN/BM could improve the ability to predicting PLN metastasis in patients with LACC, and the diagnostic efficacy of the combination of SUVLN/BM and Ds/l might be better than that of a single parameter.

Neoadjuvant chemotherapy followed by radical surgery reduces radiation therapy in patients with stage IB2 to IIA2 cervical cancer

BackgroundTo investigate whether carboplatin-liposomal paclitaxel neoadjuvant chemotherapy (NACT) benefits patients with locally advanced cervical cancer (LACC) through avoiding or delaying postoperative radiation.MethodsA total of 414 patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO 2009) stages IB2–IIA2 were included in the retrospective cohort study, who had received carboplatin-liposomal paclitaxel chemotherapy followed by radical surgery (NACT group) or primary radical surgery (PRS group) between 2007 and 2017 at our hospital. The baseline clinicopathological characteristics at diagnosis, postoperative pathological risk factors, and oncological outcomes after surgery, including postoperative radiation (as adjuvant treatment or treatment of recurrent diseases), progression-free survival (PFS), and overall survival (OS), were compared between the groups. Before treatment, the patients in the NACT group had significantly more advanced tumor stages and larger tumor sizes than those in the PRS group.ResultsThe NACT reduced the tumor volumes remarkedly with a response rate of 62.4%, and the tumors in the NACT group were smaller than those in the PRS group when the patients were subjected to radical surgery. Furthermore, postoperative pathology examination revealed less frequent deep stromal invasion in the NACT group than in the PRS group. According to the presence of pathological risk factors for recurrence, 54.82% of women in the NACT group needed adjuvant radiotherapy, while 60.87% in the PRS group, and in fact, 33.00% of NACT patients and 40.09% of PRS patients received adjuvant radiation. In addition, 8.12% of NACT patients and 9.68% of PRS patients underwent radiotherapy after relapse. The cumulative postoperative radiation rate was significantly lower in the NACT group (P = 0.041), while the differences in 5-year OS and PFS were not statistically significant between the groups.ConclusionsNACT reduces the pathological risk factors and the use of radiation without compromising survival in patients with LACC, which may protect younger patients from radiation-related side effects and subsequently improve the quality of life.Trial registrationISRCTN Registry, ISRCTN24104022

Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer.

This is an update of the Cochrane Review published in Issue 4, 2015. Cervical cancer is one of the most frequent cause of death from gynaecological cancers worldwide. Many new cervical cancer cases in low-income countries present at an advanced stage. Standard care in Europe and the US for locally advanced cervical cancer (LACC) is chemoradiotherapy. In low-income countries, with limited access to radiotherapy, LACC may be treated with chemotherapy and hysterectomy. It is not certain if this improves survival. It is important to assess the value of hysterectomy with radiotherapy or chemotherapy, or both, as an alternative. To determine whether hysterectomy, in addition to standard treatment with radiotherapy or chemotherapy, or both, in women with LACC (Stage IB2 to III) is safe and effective compared with standard treatment alone. We searched CENTRAL, MEDLINE via Ovid, Embase via Ovid, LILACS, trial registries and the grey literature up to 3 February2022. We searched for randomised controlled trials (RCTs) that compared treatments involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with LACC International Federation of Gynecology and Obstetrics (FIGO) Stages IB2 to III. We used standard methodological procedures expected by Cochrane. We independently assessed study eligibility, extracted data and assessed the risk of bias. Where possible, we synthesised overall (OS) and progression-free (PFS) or disease-free (DFS) survival in a meta-analysis using a random-effects model. Adverse events (AEs) were incompletely reported and we described the results of single trials in narrative form. We used the GRADE approach to assess the certainty of the evidence. From the searches we identified 968 studies. After deduplication, title and abstract screening, and full-text assessment, we included 11 RCTs (2683 women) of varying methodological quality. This update identified four new RCTs and three ongoing RCTs. The included studies compared: hysterectomy (simple or radical) with radiotherapy or chemoradiotherapy or neoadjuvant chemotherapy (NACT) versus radiotherapy alone or chemoradiotherapy (CCRT) alone or CCRT and brachytherapy. There is also one ongoing study comparing three groups: hysterectomy with CCRT versus hysterectomy with NACT versus CCRT. There were two comparison groups for which we were able to do a meta-analysis. Hysterectomy (radical) with neoadjuvant chemotherapy versus chemoradiotherapy alone Two RCTs with similar design characteristics (620 and 633 participants) found no difference in five-year OS between NACT with hysterectomy versus CCRT. Meta-analysis assessing 1253 participants found no evidence of a difference in risk of death (OS) between women who received NACT plus hysterectomy and those who received CCRT alone (HR 0.94, 95% CI 0.76 to 1.16; moderate-certainty evidence). In both studies, the five-year DFS in the NACT plus surgery group was worse (57%) compared with the CCRT group (65.6%), mostly for Stage IIB. Results of single trials reported no apparent difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between groups (very low-quality evidence). Hysterectomy (simple or radical) with neoadjuvant chemotherapy versus radiotherapy alone Meta-analysis of three trials of NACT with hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received NACT plus hysterectomy had less risk of death (OS) than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93; I2 = 0%; moderate-quality evidence). However, a significant number of participants who received NACT plus hysterectomy also had radiotherapy. There was no difference in the proportion of women with disease progression or recurrence (DFS and PFS) between NACT plus hysterectomy and radiotherapy groups (RR 0.75, 95% CI 0.53 to 1.05; I2 = 20%; moderate-quality evidence). The certainty of the evidence was low or very-low for all other comparisons for all outcomes. None of the trials reported quality of life outcomes. From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with LACC who are treated with radiotherapy or CCRT alone. The overall certainty of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The certainty of the evidence for NACT and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate. The same occurred for the comparison involving NACT and hysterectomy compared with CCRT alone. Evidence from other comparisons was generally sparse and of low or very low-certainty. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials assessing medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect.

Role of 18FDG PET/CT metabolic parameters in predicting hematological toxicity during chemoradiotherapy for locally advanced cervical cancer.

PurposeThe aim of this study is to evaluate the value of 18FDG PET/CT metabolic parameters in predicting hematological toxicity (HT) during chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC).Methods and materialsForty-one patients with LACC undergoing concurrent CRT were retrospectively analyzed. The correlations among age, body mass index, FIGO stage, differentiation, maximum diameter of primary lesion, parametrial invasion, lymph node metastasis, pelvic active bone marrow volume (BMACT), BMACT volume percentage (BMACT%), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and HT were analyzed using hypothesis testing and logistic regression. A p-value< 0.05 was considered significant unless otherwise specified.ResultsAmong the 41 patients, 19 had grade 3–4 HT and 22 had grade 0–2 HT. Only SUVmax (Z = −1.961, p = 0.050) and BMACT% (χ2 = 7.769, p = 0.020) showed statistically significant difference in univariate analysis. In logistic regression, grade 3–4 HT was not associated with SUVmax. The probability of HT occurrence in<30% BMACT% was 0.071 times less than in 30%–40% BMACT% (p = 0.010, OR = 0.071, 95% CI = 0.010–0.532), and the probability of HT occurrence in >40% BMACT% was 0.148 times less than in 30%–40% BMACT% (p = 0.037, OR = 0.148, 95% CI = 0.025–0.892).ConclusionBaseline 18FDG PET/CT BMACT% could help predict the severity of HT during CRT for LACC.

Outcomes and prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy

BackgroundTo investigate the prognostic factors affecting long-term survival in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively analyzed 192 naive LACC (stage IIB–IVA) patients who underwent intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy in Xiangya Hospital from January 2014 to June 2017. The clinicopathological factors of all patients were collected. To explore the relationship between factors and prognosis, survival rates were estimated by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to evaluate the effect of various factors on overall survival (OS) and progression-free survival (PFS). The nomogram and calibration curves were generated on the basis of survival analysis.ResultsThe median follow-up time was 39.5 months. There-year rates of OS and PFS were 89.1% and 82.8%. LACC patients with non-squamous cell carcinoma [NSCC, including adenocarcinoma or adenosquamous carcinoma (AC/ASC)], advanced stage (IIIA-IVA), initially positive lymph node (pelvic or para-aortic lymph node, PLN/PALN), and a lower pretreatment hemoglobin (HGB) level (< 126 g/L) had lower survival rates. In univariate analysis, patients with NSCC, advanced stage, PLN or PALN metastasis had worse OS. Patients with NSCC, advanced stage, PLN or PALN metastasis, and a lower pretreatment HGB level had worse PFS. In multivariate analysis, NSCC and PALN metastasis were independent prognostic parameters of OS. NSCC, PALN metastasis and a lower pretreatment HGB level were independent prognostic parameters of PFS.ConclusionsNSCC and PALN metastasis were poor prognostic factors of OS and PFS, a lower pretreatment HGB level was an independent prognostic factor of PFS in LACC patients treated with CCRT.

Outcome analysis of HDR compared to PDR IGABT in locally advanced cervical cancer: asingle-center cohort analysis.

This monocentric study aimed to assess the impact of technical advancement in brachytherapy (BT) on local control (LC) and cancer-specific survival (CSS) in locally advanced cervical cancer (LACC). Since 2010, 211patients with LACC have been treated with 45/50.4 Gy or 60 Gy radiochemotherapy (RTCT) followed by image-guided adaptive brachytherapy (IGABT) at the authors' institution. In 2013, combined intracavitary and interstitial brachytherapy (BT IC/IS) was implemented and in 2018, pulsed-dose-rate BT (PDR-BT) was replaced by high-dose-rate BT (HDR-BT). LC, CSS, and morbidity according to the RTOG/EORTC scoring system were analyzed. Dose-volume parameters for the high-risk clinical target volume (HRCTV) and organs at risk (OAR) were reported. While 27 (12.8%) patients died of LACC, complete local remission was achieved in 199(94.3%). Local relapse decreases with ahigh D95 in the HRCTV (hazard ratio, HR = 0.85, p = 0.0024). D95 in the HRCTV is lower after 60 Gy even if interstitial BT is used. Mean D95 in the HRCTV is 78.2 Gy, 83.3 Gy, and 83.4 Gy with PDR-BT IC, PDR-BT IC/IS, and HDR-BT IC/IS, respectively, after 45/50.4 Gy. D2cc of OARs is significantly reduced by using interstitial BT. The mean rectum and sigmoid D2cc are about 61.5 Gy with PDR-BT IC/IS and significantly decreased with HDR-BT IC/IS. This translates into alow fistula incidence. Avery low rate of severe gastrointestinal (3.4%) and genitourinary (2.3%) toxicity was observed with HDR-BT IC/IS. This large monocentric study provides further evidence that implementation of BT IC/IS has an impact on D95 in the HRCTV, LC, and CSS. There are no differences between HDR and PDR in terms of efficacy, D95 in the HRCTV, and toxicity grade ≥ 3.

Brachytherapy outcome modeling in cervical cancer patients: A predictive machine learning study on patient-specific clinical, physical and dosimetric parameters

PurposeTo predict clinical response in locally advanced cervical cancer (LACC) patients by a combination of measures, including clinical and brachytherapy parameters and several machine learning (ML) approaches. MethodsBrachytherapy features such as insertion approaches, source metrics, dosimetric, and clinical measures were used for modeling. Four different ML approaches, including LASSO, Ridge, support vector machine (SVM), and Random Forest (RF), were applied to extracted measures for model development alone or in combination. Model performance was evaluated using the area under the curve (AUC) of receiver operating characteristics curve, sensitivity, specificity, and accuracy. Our results were compared with a reference model developed by simple logistic regression applied to three distinct clinical features identified by previous papers. ResultsOne hundred eleven LACC patients were included. Nine data sets were obtained based on the features, and 36 predictive models were built. In terms of AUC, the model developed using RF applied to dosimetric, physical, and total BT sessions features were found as the most predictive [AUC; 0.82 (0.95 confidence interval (CI); 0.79 –0.93), sensitivity; 0.79, specificity; 0.76, and accuracy; 0.77]. The AUC (0.95 CI), sensitivity, specificity, and accuracy for the reference model were found as 0.56 (0.52 ...0.68), 0.51, 0.51, and 0.48, respectively. Most RF models had significantly better performance than the reference model (Bonferroni corrected p-value < 0.0014). ConclusionBrachytherapy response can be predicted using dosimetric and physical parameters extracted from treatment parameters. Machine learning algorithms, including Random Forest, could play a critical role in such predictive modeling.

International prevalence, patient and disease characteristics, and prognostic factors of locally advanced cervical cancer: A systematic literature review (418)

<b>Objectives:</b> Cervical cancer (CC) epidemiology and natural history are often reported for an overall population; however, focusing on specific groups of patients (pts), such as those with locally advanced CC (LACC), may help to understand the unique risks. We conducted a systematic literature review (SLR) to create a global picture and identify gaps in the prevalence and natural history of LACC. <b>Methods:</b> Literature databases (2010-2020) were searched for English-language observational studies reporting prevalence, pt and disease characteristics, and risk factors for pts with stages IB2-IVA CC. The proportion of pts with LACC (prevalence) in studies of all stages of CC was calculated as follows: <i>1)</i> if stage reported as I/II/III/ IV, stage II/III were deemed LACC; <i>2)</i> if stage reported as <i>in situ</i>/local- ized/regional/distant, regional was deemed LACC per SEER staging; <i>3)</i> if stage reported as FIGO group, IB2-IVA were deemed LACC. For natural history, only characteristics/prognostic factors for overall survival (OS) reported in >7 studies are discussed. <b>Results:</b> Twenty-nine studies reported CC prevalence by disease stage, without population exclusions. Six of these studies reported a high proportion of CC pts with unknown stage: Gulf nations (25%), Trinidad & Tobago (26%), Jordan (28%), South Africa (29-42%), Morocco (36%), and Kenya (54%). For LACC prevalence, the interquartile range was 26-52% among pts with CC. Lower LACC prevalence was observed in North America versus Asia, Europe, and other regions, with Asia having the highest overall prevalence (Table). Thirty studies reported natural history data for LACC pts; 13 in Asia, seven Europe, six US, two Colombia, and two in Africa. Across countries, pts with LACC had a median age of 45-55y (26 studies), Charlson/Deyo comorbidity score of 0 or 1 (seven studies), and low hemoglobin level (seven studies). Stage II was most frequent in Europe, and LACC was split between II and III in the US and Asia (Table). Lymph node (LN) involvement varied, with no clear regional trend (Table). Most studies on prognostic factors of OS for LACC pts found stage III/IVA (8/13 studies), tumor size >4-6 cm (6/9 studies), absence of chemo/ brachytherapy (6/9 studies), and positive LN (6/8 studies) predicted worse OS; age (8/11 studies) was not predictive of OS, with no consensus on histology. <b>Conclusions:</b> Median LACC prevalence was 27-47% among pts with CC globally—this is likely underestimated due to our conservative approach to calculating LACC, as well as limitations within the studies comprising this SLR (e.g., inconsistent use of staging, pts with unknown stage, etc.). Characteristics of pts with LACC were similar globally, but the stage and LN involvement varied regionally. The consensus was that stage, tumor size, treatment type, and LN status were prognostic factors for OS. Continued research and individual local assessment will be critical in aptly identifying LACC pts and their clinical profiles for optimal treatment.

Use of PET/CT for staging locally advanced cervical cancer in limited resource settings (439)

Objectives: To determine the utility of PET/CT in staging locally advanced cervical cancer (LACC) in limited-resource settings. Methods: A cross-sectional observational study of 536 records of patients with clinically proven LACC from January 2020 to June 2021 at a reference center was performed. Eighty cases suitable for analysis included a physical exam, CT, and PET/CT. CT had simple and IV contrast images; PET/CT was performed using 18-F-fluorodeoxyglucose (FDG) and simple CT images. In this specific group of individuals, PET/CT was requested because CT was consistent with advanced disease. The variables included in the evaluation were age, clinical stage, CT stage, and PET / CT stage. Descriptive statistics, Chi-square, and Cohen Kappa were performed. Results: The mean age of cases at the time of diagnosis was 48.13 years (SD ± 14). The most common stage by clinical exam was IIB (46.3%), IIIC1 (43.8%), and IIIC1 (40%) by CT and PET/CT, respectively. When comparing clinical staging and PET/CT, concordance was observed in 12% of cases and 36.2% when CT and PET were compared (k=0.352). The use of PET/CT in patients with stages IIIC1 and IIIC2 and suspicious CT upstaged 14% of cases, which was statistically significant (p=0.0001) but was not statistically useful when a CT was considered conclusive (p=0.18). Conclusions: Imaging studies are required by FIGO 2018 staging of cervical cancer. A significant difference between the use of PET/CT and CT for upstage was demonstrated in patients with stages IIIC1 and IIIC2; therefore, PET/CT as an initial study can improve the accuracy of diagnosis of patients with clinically stage III but not in other stages of LACC. However, since it occurs in a low percentage of cases, it can be omitted in limited-resource settings and replaced by CT. Clinical evaluation, even though is useful, should not be used as the only method for staging patients with LACC, and image studies must be included in the evaluation to establish an appropriate therapeutic plan and prognosis. Objectives: To determine the utility of PET/CT in staging locally advanced cervical cancer (LACC) in limited-resource settings. Methods: A cross-sectional observational study of 536 records of patients with clinically proven LACC from January 2020 to June 2021 at a reference center was performed. Eighty cases suitable for analysis included a physical exam, CT, and PET/CT. CT had simple and IV contrast images; PET/CT was performed using 18-F-fluorodeoxyglucose (FDG) and simple CT images. In this specific group of individuals, PET/CT was requested because CT was consistent with advanced disease. The variables included in the evaluation were age, clinical stage, CT stage, and PET / CT stage. Descriptive statistics, Chi-square, and Cohen Kappa were performed. Results: The mean age of cases at the time of diagnosis was 48.13 years (SD ± 14). The most common stage by clinical exam was IIB (46.3%), IIIC1 (43.8%), and IIIC1 (40%) by CT and PET/CT, respectively. When comparing clinical staging and PET/CT, concordance was observed in 12% of cases and 36.2% when CT and PET were compared (k=0.352). The use of PET/CT in patients with stages IIIC1 and IIIC2 and suspicious CT upstaged 14% of cases, which was statistically significant (p=0.0001) but was not statistically useful when a CT was considered conclusive (p=0.18). Conclusions: Imaging studies are required by FIGO 2018 staging of cervical cancer. A significant difference between the use of PET/CT and CT for upstage was demonstrated in patients with stages IIIC1 and IIIC2; therefore, PET/CT as an initial study can improve the accuracy of diagnosis of patients with clinically stage III but not in other stages of LACC. However, since it occurs in a low percentage of cases, it can be omitted in limited-resource settings and replaced by CT. Clinical evaluation, even though is useful, should not be used as the only method for staging patients with LACC, and image studies must be included in the evaluation to establish an appropriate therapeutic plan and prognosis.

Efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation for locally advanced cervical cancer: A systematic review and meta-analysis (307)

Objectives: For locally advanced cervical cancer (LACC) patients without para-aortic lymph node metastasis, the standard treatment is pelvic radiotherapy plus concurrent chemotherapy. After standard treatment, 7-15% of patients had a recurrence in para-aortic lymph nodes. The present study aimed to evaluate the efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation (EFI) for locally advanced cervical cancer (LACC). The present meta-analysis has been registered in PROSPERO (no. CRD42020167302). Methods: A systemic review and meta-analysis of recent studies retrieved from PubMed, EMBASE, and Cochrane databases from the establishment of the database to March 2021 was performed. All LACC patients with negative para-aortic lymph nodes received concurrent chemoradiotherapy. The experimental group consisted of patients undergoing pelvic irradiation plus prophylactic EFI, but the control group was undergoing pelvic irradiation. The primary outcomes were overall survival (OS) and para-aortic control. The secondary outcomes were: disease-free survival (DFS)/progression-free survival (PFS), distant metastasis, pelvic control, and toxicities. The quality of RCT was evaluated by the Cochrane bias risk tool. The quality of the retrospective study was evaluated by the Newcastle Ottawa scale (NOS). Revman5.3 software was used for statistical analysis. Results: A total of 180 studies were evaluated and six literatures met the inclusion criteria. Prophylactic EFI significantly improved 5-year OS (HR: 0.36 [0.22-0.59], p <0.0001) and DFS (3-year: HR: 0.53 [0.32-0.87], p=0.01; 5-year: HR: 0.45 [0.27-0.77], p=0.004). Prophylactic EFI reduced the rate of para-aortic failure (3-year: OR: 0.09 [0.01-0.70], p=0.02; 5-year: OR: 0.09 [0.03-0.30], p<0.0001) and distant metastasis (3-year: OR: 0.22 [0.11-0.45], p <0.0001; 5-year: OR: 0.53 [0.33-0.87], p=0.01). EFI did not increase the gastrointestinal toxicities (acute: OR: 1.94 [0.59-6.35], p=0.27; chronic: OR: 1.24 [0.65-2.40], p=0.51) and acute hematotoxicities (leukopenia: OR: 1.59 [0.98-2.59], p=0.06; thrombocytopenia: OR: 2.81 [0.87-9.03], p=0.08). Conclusions: The results of the present study suggested that prophylactic EFI using modern radiation techniques is beneficial for patients with LACC. Because five out of six pieces of literature included in our study are retrospective studies, prospective, large sample, and multicenter clinical trials are needed to further verify the impact of prophylactic EFI. Objectives: For locally advanced cervical cancer (LACC) patients without para-aortic lymph node metastasis, the standard treatment is pelvic radiotherapy plus concurrent chemotherapy. After standard treatment, 7-15% of patients had a recurrence in para-aortic lymph nodes. The present study aimed to evaluate the efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation (EFI) for locally advanced cervical cancer (LACC). The present meta-analysis has been registered in PROSPERO (no. CRD42020167302). Methods: A systemic review and meta-analysis of recent studies retrieved from PubMed, EMBASE, and Cochrane databases from the establishment of the database to March 2021 was performed. All LACC patients with negative para-aortic lymph nodes received concurrent chemoradiotherapy. The experimental group consisted of patients undergoing pelvic irradiation plus prophylactic EFI, but the control group was undergoing pelvic irradiation. The primary outcomes were overall survival (OS) and para-aortic control. The secondary outcomes were: disease-free survival (DFS)/progression-free survival (PFS), distant metastasis, pelvic control, and toxicities. The quality of RCT was evaluated by the Cochrane bias risk tool. The quality of the retrospective study was evaluated by the Newcastle Ottawa scale (NOS). Revman5.3 software was used for statistical analysis. Results: A total of 180 studies were evaluated and six literatures met the inclusion criteria. Prophylactic EFI significantly improved 5-year OS (HR: 0.36 [0.22-0.59], p <0.0001) and DFS (3-year: HR: 0.53 [0.32-0.87], p=0.01; 5-year: HR: 0.45 [0.27-0.77], p=0.004). Prophylactic EFI reduced the rate of para-aortic failure (3-year: OR: 0.09 [0.01-0.70], p=0.02; 5-year: OR: 0.09 [0.03-0.30], p<0.0001) and distant metastasis (3-year: OR: 0.22 [0.11-0.45], p <0.0001; 5-year: OR: 0.53 [0.33-0.87], p=0.01). EFI did not increase the gastrointestinal toxicities (acute: OR: 1.94 [0.59-6.35], p=0.27; chronic: OR: 1.24 [0.65-2.40], p=0.51) and acute hematotoxicities (leukopenia: OR: 1.59 [0.98-2.59], p=0.06; thrombocytopenia: OR: 2.81 [0.87-9.03], p=0.08). Conclusions: The results of the present study suggested that prophylactic EFI using modern radiation techniques is beneficial for patients with LACC. Because five out of six pieces of literature included in our study are retrospective studies, prospective, large sample, and multicenter clinical trials are needed to further verify the impact of prophylactic EFI.

Insurance status and time to first visit and initiation of radiotherapy after pathologic diagnosis for cervical cancer patients (589)

Insurance status and time to first visit and initiation of radiotherapy after pathologic diagnosis for cervical cancer patients (589)

Disparities in the quality of definitive radiation therapy for patients with locally advanced cervical cancer (059)

<b>Objectives:</b> To examine disparities and patterns of definitive radiation therapy administration for patients with locally advanced cervical cancer (LACC) and their impact on overall survival. <b>Methods:</b> Black and non-Hispanic White (NHW) patients diagnosed between 2004 and 2015 with locally advanced cervical cancer (FIGO 2009 stage IB2-IVA), who had no history of another tumor, did not undergo hysterectomy, received external beam radiation therapy of at least 45 Gy, and had at least one month of follow-up, were identified in the National Cancer Database. We examined three quality metrics described in the National Comprehensive Cancer Network (NCCN) guidelines; utilization of radio-sensitizing chemotherapy (defined as chemotherapy administered within two weeks from radiotherapy initiation), receipt of brachytherapy, and completion of radiation treatment within eight weeks from initiation. Clinical-pathologic characteristics were compared with the Chi-square test. Overall survival was evaluated with Cox models after controlling for a priori selected confounders. <b>Results:</b> A total of 9940 patients with LACC were identified; 2242 (22.6%) were Black, and 7698 (77.4%) were NHW. Black patients were more likely to have squamous cell histology (91.3% vs 84.7%, p<0.001), medical comorbid conditions (17.1% vs 14.5%, p<0.001), government-issued insurance (55% vs 46.2%, p<0.001), and be managed at academic facilities (55.6% vs 42.3%, p<0.001). Stage distribution (49.5% vs 47.2% stage III-IVA, p=0.06) and patient age (median 52 years for both groups) were comparable between Black and NHW patients. However, Black patients were more likely to receive all treatment at the reporting facility (79.3% vs 71.7%, p<0.001) and reside within a short distance (<12.5 miles) from the treatment facility (69.3% vs 47.2%, p<0.001). In the present cohort, 5432 (54.6%) patients completed treatment within eight weeks, 8794 (88.5%) received radio-sensitizing chemotherapy, and 6453 (64.9%) received brachytherapy. All three-quality metrics were met for 2981 patients (30%). Black patients were less likely to have treatment that fulfilled all three-quality metrics (26% vs 31.2%, p<0.001) even after controlling for histology, age, insurance, comorbid conditions, and disease stage (OR: 0.82, 95% CI: 0.73-0.91). Patients who received guideline conformant radiation therapy had better OS after controlling for age, comorbid conditions, disease stage, histology, and insurance (HR: 0.67, 95% CI: 0.63-0.72). A survival advantage for patients receiving guideline conformant radiation therapy was present for both WNH (HR: 0.69; 95% CI: 0.64-0.75) and Black patients (HR: 0.60, 95% CI: 0.51-0.71). <b>Conclusions:</b> Approximately one in three patients with LACC received definitive radiotherapy that met all quality metrics and had superior outcomes even after controlling for confounders. Black patients were less likely to receive guideline conformant radiotherapy than WNH, even though they reside closer to treatment facilities and are more likely to present to academic institutions.

Timing of radio-sensitizing chemotherapy initiation and impact on overall survival of patients with locally advanced cervical cancer undergoing definitive chemoradiation (358)

<b>Objectives:</b> To investigate the impact of delay in radio-sensitizing chemotherapy initiation on the survival of patients with locally advanced cervical cancer (LACC) receiving definitive chemoradiation. <b>Methods:</b> Patients diagnosed between 2004-2015 with LACC (FIGO 2009 stage IB2-IVA), who received external beam radiotherapy of at least 45 Gy, known radiation-chemotherapy interval and had at least one month of follow-up were identified in the National Cancer Database. Patients were categorized into same-day chemotherapy and radiotherapy initiation, same week (within one week from radiotherapy initiation), delayed (1-2 weeks from radiotherapy initiation), and significantly delayed (2-3 weeks from radiotherapy initiation). Overall survival was compared with the log-rank test while the Cox model was constructed to control for a priori selected confounders. <b>Results:</b> A total of 11600 patients who met the inclusion criteria were identified; 6079 (52.4%) initiated chemotherapy the same day as radiotherapy, 4513 (38.9%) initiated chemotherapy within one week, while 733 (6.3%) and 275 (2.4%) patients initiated chemotherapy 1-2 week (delayed) and 2-3 weeks (significantly delayed), respectively, after radiotherapy started. A higher percentage of patients with comorbid conditions was observed in the delayed (17.8%) and significantly delayed (15%) groups compared to the same day (12.4%) and same week (14.5%) groups, p<0.001. Similarly, a higher percentage of patients in the significantly delayed (62.9%) and delayed (54%) groups had stage III-IVA disease compared to those in the same day (45.2%) and same week (47%) groups (p<0.001). Lastly, a higher percentage of Black patients was observed in the significantly delayed (26.5%) and delayed (20.5%) groups compared to the same day (15.2%) and same week (18.3%) groups (p<0.001). Median overall survival was 103.3 and 91.93 months for same day and same week groups compared to 69.19 and 39.23 months for the delayed and significantly delayed groups (p<0.001 from log-rank). Following stratification by disease stage, there was no difference in OS between the four groups for stage IB2-II disease (p=0.17). For patients with stage III-IVA, median OS was better for patients in the same day (median: 53.68 months) group compared to those in the same week (median: 41.13 months), delayed (median: 38.28 months), and significantly delayed (median: 32.49 months) groups (p<0.001). After controlling for patient age, race, insurance status, presence of comorbid conditions, brachytherapy use, and disease stage, compared to same-day chemotherapy initiation, patients who received chemotherapy within one week (HR: 1.07, 95% CI: 1.01-1.14), 1-2 weeks (HR: 1.14, 95% CI: 1.01-1.28) or 2-3 weeks (HR: 1.32, 95% CI: 1.12-1.57) after radiotherapy initiation had worse overall survival. <b>Conclusions:</b> Any delay in administering radio-sensitizing chemotherapy relative to radiotherapy initiation may be associated with a detrimental effect on the survival of patients with LACC, especially for those with stage III-IVA disease. Same-day initiation of chemotherapy with radiation should be encouraged.

Anlotinib plus chemoradiotherapy in the treatment for FIGO stage IB3 and IIB-IVA cervical cancer: A prospective single-arm, single-center, exploratory phase II trial (299)

<b>Objectives:</b> Cervical carcinoma is the fourth leading cause of cancer-related death among women worldwide. Previous randomized clinical trials showed a 30% to 50% decrease in risk of death in locally advanced cervical cancer (LACC) with the addition of concurrent platinum-based chemoradiotherapy when compared with radiotherapy alone. Mechanisms to account for improved efficacy are thought to include direct cytotoxicity, radiosensitization of tumor cells, and control of subclinical metastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib synergizes with radiation and cisplatin, as shown in preclinical and clinical studies. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to concurrent chemoradiotherapy in FIGO stage IB3 and IIB-IVA cervical cancer. <b>Methods:</b> Inclusion criteria include treatment-naive histologically confirmed FIGO stage IB3 to IVA cervical cancer with at least one measurable lesion and ECOG performance score 0-2 within the age range of 18 to 75 years. Abundant organ functions are required, with no contraindication to anlotinib or chemoradiation present. Patients will be treated with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total 3 cycles) and X-ray external-beam radiotherapy (total 45Gy-50Gy in 25-28 fraction), followed by brachytherapy (6Gy/5 fractions or 7Gy/4 fractions) with concurrent cisplatin (40 mg/m2 weekly for 5-6 weeks). The primary endpoint is the progression-free survival (PFS) rate at three years. The secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and quality of Life (QOL). Safety will be evaluated in all patients who receive study drugs according to the treatment received (safety population) by recording clinical adverse events (AEs) using National Cancer Institute Common. The sample size calculation of 47 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test; considering a 10% reduction, a total of 53 samples are required. This study is currently open, and 23 patients have been enrolled. The estimated primary completion date is December 1, 2024, and the estimated study completion date is October 31, 2025.

Is There a Place for Adjuvant Chemotherapy in the Treatment of Locally Advanced Cervical Cancer?

Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.