Objective This study aimed to assess factors contributing to the survival disparity between insured Black and White patients with uterine cancer treated within the same large US health care system. Methods This is a retrospective cohort analysis of Black and White patients diagnosed with uterine cancer from 2005 to 2022 while members of a large community-based integrated US health care system. Five domains of factors potentially contributing to survival were characterized: co-morbidities, diagnostic process, treatment, tumor characteristics, and socioeconomic factors. Using logistic regression, propensity scores were calculated and used to sequentially balance Black and White patients for each of these domains, evaluating the effect of balancing each domain on the hazard ratio (HR) for 5-year mortality for Black versus White patients. Results Comparing 11,878 White with 2196 Black patients, the HR for 5-year mortality for Black patients, adjusted for baseline characteristics and co-morbidities, was 2.05 (95% confidence interval [CI] 1.79 to 2.33). Substantial reductions in excess mortality were observed after balancing tumor factors, which reduced the HR to 1.31 (95% CI 1.11 to 1.53), and socioeconomic factors, which further reduced the HR to 1.08 (95% CI 0.91 to 1.28). No significant reduction was observed after balancing co-morbidity, diagnostic, or treatment factors. Conclusions Among insured patients treated within the same US health care system, Black patients had approximately twice the mortality risk of White patients, with 70.8% of the excess relative risk of death among Black patients being attributable to tumor characteristics, 21.4% attributable to socioeconomic status, and 7.8% un-explained. Co-morbidities, diagnostic efficiency, and treatment quality were not significant contributors relative to other factors. These findings suggest that eliminating disparities in survival between Black and White patients will require development of more effective treatments for high-risk tumor types and interventions that mitigate the negative effects of lower socioeconomic status on health.

Recent updates to national guidelines recommend primary human papillomavirus (HPV) screening for routine cervical cancer screening alongside previously recommended screening options. However, limited guidance exists for implementation approaches that best facilitate cancer screening practice substitution and achieve optimal stakeholder-centered outcomes. We compared “centrally-administered + locally-tailored” (here after referred to as locally-tailored) vs. “centrally-administered + usual care” (here after referred to as centrally-administered) approaches for achieving substitution of HPV and cytology co-testing with primary HPV screening for routine cervical cancer screening to examine the effect of local tailoring on implementation and stakeholder-centered outcomes. We conducted a pragmatic, cluster randomized trial embedded in the Kaiser Permanente Southern California (KPSC) health system, randomly assigning site groups to study arms at the level of the geographic service area (12 service area randomized). The study took place between 2020–2022. Centrally-administered implementation strategy bundles included physician and staff educational activities. Sites in the locally-tailored arm underwent local needs assessment followed by local selection, tailoring and deployment of implementation strategy bundles. The primary outcome was the proportion of primary HPV screenings among all screenings performed. Secondary stakeholder-centered outcomes included patient (knowledge, emotional reaction, satisfaction, volume of patient inquiries) and provider outcomes (perception, knowledge, acceptance, and satisfaction) measured via repeated surveys or electronic health records. The generalized estimating equation framework and the difference-in-differences approach were used to compare outcomes across study arms. The proportion of appropriate screenings (i.e., use of primary HPV screening) during the post-intervention period was high, with no observed difference between study arms: 98.4 https://clinicaltrials.gov/study/NCT04371887?cond=primary .

IntroductionPrimary human papillomavirus(HPV) testing is recommended for cervical cancer screening for women aged 30–65 years without a history of abnormal results. However, there is little clear guidance regarding effective strategies for implementing primary HPV screening. As part of an ongoing randomized trial comparing implementation strategies for primary HPV testing (a centrally administered + usual care strategy vs. centrally administered + locally tailored strategy), we evaluated clinician experiences and perceptions of large-scale implementation of primary HPV screening in an integrated healthcare system, Kaiser Permanente Southern California.Materials and methodsWe conducted qualitative interviews with internal medicine, family medicine and obstetrics/gynecology clinicians to gain insight into fidelity to the interventions and implementation strategies, barriers and facilitators to implementation, and recommendations. Participants from both arms of the trial were recruited. Interview guides were developed with the Consolidated Framework for Implementation Research (CFIR). We recruited physicians, licensed vocational nurses, and medical assistants after primary HPV screening had been implemented. Interviews were recorded and transcribed. Using a team coding approach, we developed an initial coding structure refined during iterative analysis; data were subsequently organized thematically into domains, key themes, and sub-themes using thematic analysis, followed by framework analysis informed by CFIR.ResultsThirty-two interviews were conducted. Participants in both arms of the trial noted high awareness, preparedness, buy-in, and fidelity to the new screening process. Initial barriers concerned specimen collection, proper ordering, and lab delays. An unanticipated barrier was the length of time needed to return lab results for reflexive cytology tests after a positive HPV result which reportedly increased patient anxiety. Participants in both arms reported fidelity to the centralized strategy (e.g., attending webinars, leadership announcements). In the local-tailored arm, few participants recalled the local-tailored resources.DiscussionThe centralized strategy was perceived as highly acceptable and feasible, and fidelity to the associated interventions appear to be facilitators of practice change. Recommendations for improving implementation included patient education, outreach and ongoing clinician training. Findings can be applied to other health systems and settings considering primary HPV screening implementation, particularly those within the U.S. or with a similar health care model. Trial RegistrationClinicalTrials.gov, identifier #NCT04371887

BACKGROUND:Timeliness of colposcopy follow-up after primary human papillomavirus screening has not been well examined. OBJECTIVE:We evaluated time to colposcopy follow-up among women with an abnormal primary human papillomavirus screening result overall and by human papillomavirus genotype, triage cytology results, race/ethnicity, and neighborhood deprivation index. STUDY DESIGN:Women aged 30 to 65 years who received primary human papillomavirus screening at Kaiser Permanente Southern California from July 15, 2020, to December 31, 2021 and had screening results that required colposcopy follow-up were identified. All data were collected from Kaiser Permanente Southern California's electronic medical records. Multivariable modified Poisson models were used to evaluate the associations between human papillomavirus type and triage cytology results, race/ethnicity, neighborhood deprivation index, and receiving a colposcopy within 3 months and 6 months of screening results. RESULTS:A total of 5833 women were included. The mean age was 42.9 years; 11.4%, 9.8%, 48.7%, and 24.4% were of Asian/Pacific Islander, non-Hispanic Black, Hispanic, and non-Hispanic White race/ethnicity. Overall, 71% and 78% received colposcopy within 3 and 6 months of screening, respectively. Compared with women with non-16/18, other high-risk human papillomavirus types and low-grade cytology results, women with HPV 16/18 with normal low-grade or high-grade cytology results and women with other high-risk human papillomavirus and high-grade cytology results were more likely to have colposcopy within 3 months of screening results [risk ratio ranged from 1.21 (95% confidence interval, 1.16-1.25) to 1.34 (95% confidence interval, 1.25, 1.42)]. Non-Hispanic Black women (vs non-Hispanic White, risk ratio=0.93 [0.87, 1.00]) and women from the most deprived neighborhoods (vs least deprived, risk ratio=0.95 [0.90, 1.00]) had lower likelihoods of receiving colposcopy within 3 months of screening. Findings for 6 months of follow-up were similar to that of 3 months. CONCLUSION:Our observations confirmed prioritization of diagnostic follow-up for women with human papillomavirus 16/18+ as well as high-grade cytology results. Barriers to incomplete colposcopy follow-up and disparity should be better understood and addressed.

PURPOSE:Demand for germline hereditary cancer genetic testing has increased because of reduced cost, gene discovery, expanding indications, and precision cancer therapies. The traditional model for germline testing, where a genetics provider performs all steps of the testing process (pretest counseling, test ordering, results disclosure, and post-test counseling), is no longer able to meet testing needs especially for patients with cancer needing timely germline testing for treatment decisions. Mainstreaming has emerged as an alternative approach to increase testing capacity and efficiency, where nongenetics providers perform these steps and genetics providers focus on post-test counseling for positive results. METHODS:This study reports a 3-year experience with mainstreaming hereditary cancer gene panel testing at Kaiser Permanente Southern California. The study compared demographic characteristics, cancer diagnoses, and test results between patients tested by genetics providers (traditional model) versus nongenetics providers (mainstreaming) over 3 years. Over 32,000 germline hereditary cancer gene panels were completed, including nearly 12,000 mainstreaming tests. RESULTS:Mainstreaming substantially increased testing volume. Patients undergoing mainstream testing were more likely to have cancer, be male, and self-report being Asian or Black. The positive test rate was slightly lower in the mainstreaming group (11%) compared with the traditional testing model (15%), with similar rates of variants of uncertain significance. Post-test genetic counseling was high in both groups for positive results. CONCLUSION:This study demonstrates that mainstreaming can be successfully implemented in a large health care system and significantly expand testing capacity.

INTRODUCTION:In 2018, the US Preventive Services Task Force updated cervical cancer screening recommendations to allow for screening every 5 years with primary human papillomavirus (HPV) testing in combination with cytology (cotesting) or every 5 years with primary HPV screening alone. Despite these changes, the uptake of primary HPV screening has been lower than expected. The purpose of this study was to evaluate the patient perspective of an integrated health system transition from cotesting to primary HPV testing among a 30- to 65-year-old cohort. METHODS:Semistructured phone interviews were conducted from July to December 2023 at Kaiser Permanente Colorado with 16 members aged 30-65 years. Interviews asked about reactions to the forthcoming change in cervical cancer screening, personal concern about cervical cancer risk, feedback on patient-facing education materials, and preference on communication timing and modality. RESULTS:Participants reported concerns about cervical cancer screening intervals, primarily the reduction in frequency leading to underdiagnosis of sexually transmitted infections (STIs). Participants recommended defining the rationale for the change to primary HPV testing in the patient education materials. Participants preferred communication about the change in-clinic between practitioner and patient. DISCUSSION:The interviews identified key themes, including the differentiation between cervical cancer and STI screening methodologies, potential underdiagnosis of STI and cervical cancer, and the rationale supporting primary HPV testing and associated screening intervals. CONCLUSION:These qualitative findings can inform health systems of potential patient concerns to address when considering the transition from cotesting every 3 years to primary HPV testing every 5 years for cervical cancer screening.

BACKGROUND:Disparities in ovarian cancer survival for African American women are multifactorial. We evaluated racial and ethnic differences in time to ovarian cancer surgery in members of an integrated health care system. PATIENTS AND METHODS:In this retrospective cohort study, we identified women diagnosed with invasive epithelial-type ovarian cancer between January 1, 2008, through December 31, 2014, at an integrated health care system in the United States. We extracted data on cancer-related variables and sociodemographic variables from the health care system's cancer registry and electronic health records. We included patients who received ovarian cancer surgery without neoadjuvant chemotherapy. We defined time to surgery as the number of days between diagnostic imaging study and surgery. We used Cox proportional hazards regression to evaluate crude and adjusted association of race and ethnicity with time to surgery. RESULTS:Of 872 patients included, 55.1% were non-Hispanic White (hereafter, White), 24.9% were Hispanic, 14.6% were Asian/Pacific Islander (PI)/Native American, and 5.5% were African American. Median age at diagnosis was 59.0 years. African American patients were diagnosed at an older age and were more likely to come from deprived neighborhoods than other racial and ethnic groups. Median time to surgery was longer for African American patients compared with White, Hispanic, and Asian/PI/Native American patients (median days: 27.5 vs 21.0, 24.5, and 26.0, respectively; P<.0001). In adjusted models, the likelihood of having received surgery at any given time post diagnostic imaging was 31% lower for African American patients compared with White patients (HR, 0.69; 95% CI, 0.51-0.93). This likelihood was also lower for Hispanic and Asian/PI/Native American patients, but not statistically significant. CONCLUSIONS:Our findings showed that patients with ovarian cancer from racial and ethnic minorities had a lower likelihood of having received surgery at any given time post diagnostic imaging compared with White patients, demonstrating that racial and ethnic differences exist in time to ovarian cancer surgery in patients with relatively equal access to care.

Background: Current clinical guidelines recommended primary human papillomavirus (HPV) screening for cervical cancer testing. Previous studies reported patient-level barriers (e.g., limited knowledge and attachment to Pap test) that may hinder wide adoption of primary HPV screening. We assessed these women-level factors following the implementation of primary HPV screening (July 2020) at Kaiser Permanente Southern California (KPSC).Methods: We administered a patient survey (mail and on-line) to female KPSC members aged 30-65 years who received primary HPV screening between October and December 2020. Those who preferred English vs. Spanish language were sampled separately. The survey included domains on knowledge about HPV and HPV screening, awareness of screening guidelines, and attitudes about HPV testing. Demographic data were collected using electronic health records. We used weighted multivariable logistic and modified Poisson regressions for associations between language preference and survey responses.Results: In total, 3,009 surveys were returned (38.0% response rate). Few women (7.0%) found HPV testing as an acceptable screening method. The majority of women (92.2%) remained unaware that HPV testing can replace Pap test for screening. The Pap test was the most preferred screening approach for 33.2% Spanish-speaking women vs. 19.9% English-speaking women. Only 20.6% knew that women aged 30-65 years can be screened every 5 years with cotest or primary HPV screening. Most women (96.4%) did not perceive stigma about taking the HPV test.Conclusion: Proactive patient education will help improve women's knowledge about primary HPV screening, which may facilitate its implementation in additional health care settings.

577 Background: Adhering to National Comprehensive Cancer Network (NCCN) Guidelines correlates with higher survival in ovarian cancer and serves as a measure of care quality. Adherence to guidelines however is relatively low, routinely reported to be less than 50%. Integration of clinical pathways into the Electronic Medical Record (EMR) is a practical approach to incorporate decision-making tools in a user-friendly interface, ensuring appropriate diagnostic testing and treatment is offered to all ovarian cancer patients. Kaiser Permanente (KP) is an integrated national healthcare delivery organization caring for 12.7 million patients across the United States. Embedded clinical pathways created by KP optimize clinical decision-making and provide treatment recommendations according to established evidence-based guidelines. This report presents data on the adherence to ovarian cancer clinical pathways within KP. Methods: Beginning in January 2021 a multidisciplinary national team at KP (gynecologic and medical oncologists, pharmacists, geneticists, pathologists, and radiation oncologists) established evidence-based clinical pathways for ovarian cancer treatment which were subsequently integrated into the Epic Systems EMR. Oncologists can use the pathways to place diagnostic and treatment orders for patient care. EMR data analytics were utilized to track adherence to the consensus-defined clinical pathways among treatment orders placed for ovarian cancer within KP nationally between January 2021 and February 2023. Treatments were considered adherent for which the order was placed through the pathway; treatments for ovarian cancer indications ordered outside of the pathway interface were non-adherent. Results: Between January 2021 and February 2023, 3721 treatment plans were initiated within KP nationally for ovarian cancer, for a median 144 plans monthly. Adherence nationally to the ovarian cancer treatment pathway varied from 16% monthly at inception to 64% in early 2023 with a high of 71% in late 2022. The median pathway adherence rates per quartile were 20%, 37%, 59%, 55% in 2021, and 62%, 66%, 70%, 67% in 2022, and 64% in January through February 2023. The increases in adherence were consistent between geographic regions and indications of treatment. Conclusions: Integration of clinical pathways into the EMR is a promising means of encouraging appropriate testing and therapy for ovarian cancer. As clinicians retained the option to initiate treatment orders outside of the embedded KP pathways, our data is limited to measuring KP pathway use, not evaluating whether treatments given were concordant with NCCN Guidelines. Treatments initiated outside the pathway may still be concordant with national guidelines. Measurement of pathway adherence is useful however to describe effective diagnostic and treatment pathway implementation across a large healthcare organization to facilitate the delivery of optimal care.

To quantify the incidence of COVID-19 infection among patients receiving anti-PD1 checkpoint immunotherapy for gynecologic malignancy in an integrated healthcare system. Patients with recurrent/metastatic endometrial or cervical carcinoma who received pembrolizumab (200 mg IV q3wks or 400 mg IV q6wks) within the Southern California Kaiser Permanente Medical Group (SCKPMG) from December 11, 2020 through July 1, 2022 were retrospectively evaluated for COVID-19 infection. The Electronic Medical Record (EMR) was used to abstract the following data: type of cancer, vaccination status, vaccination date, number of doses, documented COVID-19 infection, date of COVID-19 infection if present, age, and BMI. Patients with COVID-19 infection within 14 days of initial dose of vaccination were excluded. 4,521 patients with a diagnosis of endometrial or cervical cancer were treated at one of eight SCKPMG hospitals during the study period. 178 patients (3.9%) received pembrolizumab (cervical cancer: n=37; endometrial cancer: n=141) and 154 (86.5%) of the combined study population were vaccinated. Patients with cervical cancer and those with endometrial cancer received similar doses and schedules (p=0.817) Nineteen percent (n=36) of the combined study population were diagnosed with COVID-19. Using logistic regression, an inverse relationship between Pembrolizumab dose and rate of COVID-19 was noted (p=0.0332, 95% CI: –0.0998 to –0.0033 percent decrease in COVID infection rate per 100 mg). This finding was more pronounced in patients with cervical cancer (p=0.0279, 95% CI: –0.201 to –0.011). Download : Download high-res image (90KB)Download : Download full-size image I-O may modulate the clinical sequelae of COVID-19 infection, regardless of vaccination status among women with recurrent/metastatic endometrial or cervical cancer.

TPS5625 Background: Oregovomab, a murine IgGκ1 monoclonal antibody with high affinity binding to tumor associated antigen CA125, renders the target antigen CA125 more immunogenic or “neoantigen-like”. The proposed mechanism action is enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when oregovomab is combined with chemotherapy. In a randomized phase II study, oregovomab, in combination with paclitaxel and carboplatin, (PC) induced tumor immunity and demonstrated significant improvement in median PFS (41.8 months(m) PCO vs 12.2 m PC, HR 0.46, p = 0.0027) and median OS (N.E. PCO vs 43.2 m PCP, HR 0.35, p = 0.043) in patients with previously untreated EOC. Patients receiving adjuvant chemotherapy were included. Oregovomab combined with PC had a favorable toxicity profile. FLORA-5/GOG3035, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: In this phase 3, multicenter, double-blind, placebo-controlled trial, optimally debulked patients with FIGO III/IV EOC and serum CA125 ≥ 50 U/ml receiving adjuvant (Cohort 1) or patients receiving neoadjuvant chemotherapy post-interval cytoreductive surgery (Cohort 2) will be randomized to PC + oregovomab or placebo (PCO vs. PCP). Patients with germline BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with an additional dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients will be administered oregovomab/placebo after debulking surgery at cycles 4 and 6 with two additional doses at 6- and 18-weeks following cycle 6 in Cohort 2. No other front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim futility analysis will be performed. Secondary objectives include OS, frequency and severity of AEs, and QoL. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of correlative biomarkers. The study is actively enrolling in the US, Canada, Belgium, Italy, Spain, Czech Republic, Hungary, Poland Korea, Taiwan, Mexico Argentina, India and Chile. 518 of the planned 602 patients were enrolled at the time of submission. Clinical trial information: NCT04498117 .

Objectives Oregovomab (O), a murine IgG? monoclonal antibody binds to tumor-associated antigen, CA125, rendering target CA125 more immunogenic through enhanced antigen processing and presentation to specific T cells, bypassing tumor-associated suppression and resulting in enhanced efficacy of chemotherapy. In a randomized phase II study, oregovomab in combination with paclitaxel and carboplatin (PC) demonstrated significant improvement in PFS (median (months) 41.8 PCO vs 12.3 PC, HR=0.46, p=0.0027 and OS median N.E. PCO vs 43.2 PC, HR=0.35, p=0.043. FLORA-5/GOG-3035 is the confirmatory global registration trial. Methods Optimally debulked patients with FIGO III/IV epithelial ovarian cancer and serum CA125 > 50 U/ml randomized to PC ± oregovomab. Patients with BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in two cohorts. In Cohort 1 (adjuvant), oregovomab/placebo is administered at cycles 1, 3, and 5 of chemotherapy and at 12 weeks following cycle 5. In Cohort 2 (neoadjuvant), oregovomab/placebo will be administered at cycles 4 and 6 of chemotherapy, and at 6- and 18-weeks following cycle 6. No other post front-line maintenance therapy is permitted. The primary objective is PFS by RECIST 1.1 criteria. Cohort 1 will recruit 372 patients and Cohort 2 will recruit 230 patients. Secondary objectives include OS, frequency and severity of adverse events, and quality of life. 137 sites in US, Canada Asia, Europe and South American are actively enrolling. 324 patients have been randomized. Results Trial in progress: there are no available results at time of submission. Conclusions Trial in progress: there are no available conclusions at time of submission.

Background: Limited guidance exists regarding implementation strategies that best facilitate cancer screening practice substitution and achieve optimal stakeholder-centered outcomes. Here we describe the protocol for a randomized pragmatic trial comparing two implementation strategies to facilitate substitution of primary HPV screening for Pap and HPV co-testing to perform routine cervical cancer screening of women aged 30-65 years at Kaiser Permanente Southern California (KPSC). Methods: Twelve service areas within KPSC will be randomized to a "centrally-administered system-wide implementation + local-tailored implementation" strategy or a "centrally-administered system-wide implementation only" strategy. The centrally-administered strategy comprises clinician and staff educational activities. Sites in the local-tailored arm will then conduct a structured local needs assessment followed by site-specific selection and deployment of implementation interventions. Surveys and interviews will be conducted among women and providers from the primary care and ob/gyn departments prior to the system-wide transition, shortly after the transition, and after the completion of local-tailored interventions. A stakeholder advisory committee will assist with study design, defining stakeholder-centered outcomes, and developing data collection tools. Results: The primary outcome of interest is uptake of primary HPV screening. Secondary provider-centered outcomes include provider knowledge, delivery of patient education, satisfaction with the practice substitution process, and resistance to primary HPV screening. Secondary patient-centered outcomes include patient knowledge, stigma, and satisfaction with the screening process. Intervention fidelity will also be measured via surveys. Conclusions: Findings from this study will help inform future use of a local-tailored implementation strategy for adopting primary HPV screening at large health care systems. Findings may also be applicable to other types of practice substitution.

Objectives: 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. Methods: 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. Objectives: 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. Methods: 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.