Induction chemotherapy (IC) added to chemoradiation (CRT) in locally advanced cervical cancer (LACC) improves survival at the expense of adverse events (AEs), 99 % with IC/CRT vs 95 % CRT alone, 59 % vs 48 % G3/4 AEs. We investigated the impact of this on quality of life (QoL).

500 women with FIGO 2008 stage IB1 node positive, IB2, II, IIIB and IVA cervical carcinoma were randomised to CRT alone or IC (6 weeks carboplatin AUC2 paclitaxel 80mg/m2) followed by CRT. QoL questionnaires (EORTC QLQ-C30 v3, QLQ-CX24) were completed at baseline, D1 week 4 IC, D1 CRT, D1 week 3 CRT, 4 weeks post CRT and all follow up visits. Mixed modelling for repeated measures was used to compare the groups during trial treatment to 2 years follow up (adjusting for baseline).

QoL (global health status, physical and social functioning) slightly worsened during IC and symptom experience slightly improved. Emotional functioning improved during IC. Peripheral neuropathy was slightly worse with IC/CRT. Fatigue and nausea/vomiting worsened from baseline to week 4 IC whilst pain and diarrhoea improved, consistent with reported AEs. Over the whole period, mean differences for these symptoms between the treatment groups was small and not clinically significant and resolved by 12-18 months. In all cases, mean score differences during trial treatment until 2 years post CRT showed only small differences (<5 units) not meeting the threshold for clinical relevance.

IC added to CRT does not adversely impact QoL compared to CRT, either during IC, during CRT or later.

Cervical cancer is the leading cause of cancer-related deaths for women in South Africa. The standard of care treatment for locally advanced cervical cancer (LACC) is external beam radiation followed by brachytherapy with concurrent platinum-based chemotherapy. There exists a paucity of data regarding the treatment regimens received by women with LACC in South Africa. The aim of this study is to assess the patterns of care and survival for patients with LACC treated with curative intent at a tertiary care center in South Africa.

This is a retrospective review of cervical cancer patients with histologically confirmed LACC (stage IB2-IVA) who underwent radiation with curative intent at Groote Schuur Hospital in Cape Town, South Africa between July 2013 and July 2018. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method. Cox proportional hazards modeling analyzed patient and treatment factor associations with survival. Logistic regression modeling was performed to assess factors associated with the receipt of chemotherapy and baseline hemoglobin.

Among 278 patients, 28.4% (n = 79) of women had co-infection with HIV, and 64.8% (n = 180) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2-year OS (87.4% vs. 52.8%, p < 0.001) and DFS (80.2% vs. 58.3%, p < 0.001) compared to those receiving radiation alone. Factors associated with improved OS were receipt of chemotherapy (HR 0.32, p = 0.005) and higher baseline hemoglobin (HR 0.86, p = 0.018). Upon multivariate logistic regression, adjusting for age, stage, and HIV status, patients with stage III/IV disease were less likely to receive chemotherapy (HR 48.17, p < 0.001) and were less likely to have hemoglobin ≥ 10 g/dL (HR 0.20, p < 0.001).

Addition of chemotherapy to standard radiation improved OS in women with LACC, regardless of HIV status. Our findings add to a body of literature highlighting the importance of providing concurrent chemoradiotherapy to all patients with LACC, including persons living with HIV and those with stage III/IV disease.

Cervical cancer is preventable with screening and vaccination approaches; however, access to these preventative measures is limited both nationally and globally and thus many women will still develop cervical cancer. Novel treatments and practice-changing research have improved cervical cancer outcomes over the past few decades. In this Review, we discuss clinical trials that have refined or redefined the treatment of cervical cancers across the early stage, locally advanced, persistent, recurrent and/or metastatic disease settings. Advances for patients with early stage disease have been achieved through trials evaluating less extensive and fertility-preserving surgeries, different surgical approaches (open versus minimally invasive), and sentinel versus full pelvic lymph node dissection. We also discuss results from trials testing the use of neoadjuvant, induction and adjuvant chemotherapy as well as immune-checkpoint inhibitors in patients with locally advanced disease. Finally, we review the progress made with systemic chemotherapy and novel therapeutics, including anti-angiogenic agents, immune-checkpoint inhibitors and antibody-drug conjugates, in the setting of metastatic and/or recurrent cervical cancer. The advances highlighted in this manuscript have reduced morbidity and improved overall survival for patients with this challenging-to-treat disease, while also inspiring additional research and trials in the field.

Cervical cancer is a formidable global health issue, particularly affecting women in lower-middle-income countries with little or no access to preventative vaccines, screening programs, and treatment modalities. The case report presents a unique case of a large cervical cancer achieving complete response (CR) with concurrent chemoradiotherapy (CCRT), highlighting the effectiveness of this treatment approach even in advanced stages and underscoring the importance of adaptive radiotherapy (RT) in optimizing patient outcomes.

We present the case of a 53-year-old woman who presented with four years of abnormal vaginal bleeding and was found to have p16-positive, moderately differentiated cervical squamous cell carcinoma. The tumor measured 14 cm × 12 cm × 8 cm, the largest size reported in the literature to achieve CR with CCRT. Despite this monumental feat, the patient remained disease-free and is currently on follow-up for 2 years; however, she continued to suffer from substantial morbidity caused by a vesicovaginal fistula and hydronephrosis, underscoring the continuing impact of cervical cancer on quality of life.

In this case report, we highlight the effectiveness of CCRT in achieving CR, even in cases of bulky cervical cancer, with adaptive RT offering a customized strategy to improve patient outcomes. We also emphasize the necessity for multidisciplinary team discussions and highlight the need for strategies to mitigate treatment-related toxicities and long-term complications.

One of the most significant breakthroughs in cancer research has been the identification of persistent infection with certain human papillomaviruses (HPV) genotypes as the cause of cervical cancer. Since then, a range of diagnostic and therapeutic methods has been developed based on this discovery. This article aims to describe the latest updates in the biology, prevention, and treatment of HPV-related cervical cancer. The current state of knowledge regarding vaccinations, diagnostic tests, and cervical cancer therapies is presented. The latest WHO guidelines on vaccinations are presented, as well as announcements of upcoming changes. The final part of the article summarizes promising new diagnostic and treatment methods, as well as perspectives and the latest research findings on self-administered diagnostic tests, the use of therapeutic vaccines, and circulating cell-free DNA in diagnosis. Despite the significant progress made in recent years, the strategy based on vaccination and testing remains the cornerstone in the fight against HPV-related cervical cancer.

The standard treatment for cervical tumors larger than 4 cm, known as bulky tumors, currently involves concurrent chemoradiotherapy followed by vaginal brachytherapy. However, radical surgery is an alternative option in some cases, particularly for those in which a combination of risk factors is not anticipated. Recent studies show that neoadjuvant chemotherapy may help reduce tumor size in these bulky tumors, enabling subsequent surgical intervention reducing the adverse effects derived from radiotherapy. Evidence about fertility sparing surgery in patients with bulky tumors is limited, although some retrospective studies reported good oncological outcomes when adequate tumor reduction is achieved through neoadjuvant chemotherapy. Moreover, the administration of adjuvant radiotherapy after radical surgery in patients with tumor sizes ≥ 4 cm in the final pathological report, combined with other intermediate risk factors for recurrence, remains a topic of debate. Current evidence indicates no significant differences in overall survival or disease-free survival between follow-up alone and the use of adjuvant radiotherapy in these cases, although further research is needed to refine treatment strategies for these patients. This narrative review aims to summarize the available evidence on the comprehensive management of bulky cervical tumors, addressing relevant issues and controversies in the field.

Radiation therapy plays a critical role in the management of locally advanced vulvar cancers but can lead to a unique spectrum of side effects, with >25% of patients experiencing high-grade toxicities. The treatment phase requires meticulous perineal skincare and may require pharmacologic management of dysuria and cystitis, diarrhea, nausea, and dermatitis/mucositis. The addition of chemotherapy warrants close laboratory monitoring for hematologic and metabolic derangements.

This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dual-agent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events.

This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching.

Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3-4 acute haematological toxicities was different between the two groups (p<0.05).

Cisplatin combined with paclitaxel CCRT couldn't improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.

This review discusses the relationship between inflammation and cancer initiation and progression, which has prompted research into anti-inflammatory approaches for cancer prevention and treatment. Specifically, it focuses on the use of inflammation-reducing agents to enhance the effectiveness of tumor treatment methods. These agents are combined with platinum(II)-based antitumor drugs to create multifunctional platinum(IV) prodrugs, allowing for simultaneous delivery to tumor cells in a specific ratio. Once inside the cells and subjected to intracellular reduction, both components can act in parallel through distinct pathways. Motivated by the objective of reducing the systemic toxicity associated with contemporary chemotherapy, and with the aim of leveraging the passive enhanced permeability and retention effect exhibited by nanostructured materials to improve their accumulation within tumor tissues, the platinum(IV) complexes have been efficiently loaded into mesoporous silica SBA-15 material. The resulting nanostructured materials are capable of providing controlled release of the conjugates when subjected to simulated plasma conditions. This feature suggests the potential for extended circulation within the body in vivo, with minimal premature release of the drug before reaching the intended target site. The primary emphasis of this review is on research that integrates these two approaches to develop chemotherapeutic treatments that are both more efficient and less harmful.

External beam radiotherapy (EBRT) became unavailable in Uganda from February 2016 to November 2017. Following resource stratification guidelines, an alternative treatment strategy was developed.

Bulky early stage to Stage IIIB patients received at least 3 cycles of neoadjuvant chemotherapy (NAC). Surgery was performed if adequate response was achieved and adjuvant therapy given for high risk factors. Chemotherapy versus supportive care was advised in unresectable disease. NAC protocol completion was defined as receiving at least 3 cycles of NAC followed by either surgery, chemotherapy and/or radiation, or best supportive care. The purpose of this study was to determine the completion rate of NAC and assess the adverse events associated with treatment. Data were collected through retrospective chart review.

From February 2016 to November 2018, 53 evaluable patients were identified. 86.8% (46/53) of patients presented in Stage IIB or higher. The completion rate of the NAC protocol was 75.5% (40/53). 94.3% (50/53) received platinum-taxane combination. 7.6% (4/52) grade 3 adverse events occurred related to chemotherapy, all hematologic. 18.8% (10/53) patients underwent surgery with 2 aborted cases due to metastatic or inoperable disease. No adverse events related to surgery were reported. 5 patients underwent adjuvant therapy after surgery due to high risk factors or incomplete pathology findings. 26 patients received adjuvant radiation (3 brachytherapy, 23 EBRT after it became available). Reported side effects related to radiation included vaginal fibrosis and skin reactions.

In this limited-resource setting, majority of patients completed a NAC treatment strategy for cervical cancer with acceptable toxicities.

Among cervical cancers, adenocarcinoma is less common than squamous cell carcinoma of the cervix; however, the incidence of these cancers is rising. The incidence has changed largely due to a shift in risk factors as well as the evolution of the diagnosis and classification of adenocarcinoma. Adenocarcinoma of the cervix is composed of a diverse group of neoplasms that can be classified by various factors. In this review article, preinvasive disease, updated classifications of adenocarcinoma, and treatment options for cervical adenocarcinoma are discussed with a focus on current and future therapies. Advances in antibody-drug conjugates (ADC) and immunotherapy have increased the treatment options available for usual-type adenocarcinoma but there is still a lack of variety of treatment options for the remaining 25% of non-usual-type adenocarcinomas.

To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer.

Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15).

191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn't (31.27 (SD 32.5) months).

Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

Cervical adenocarcinoma is the second most common histology of cervical cancer and treatment can involve surgery, radiotherapy, systemic therapy, and any combination of the three. Photon external beam radiation therapy and brachytherapy have been the mainstay of radiation treatment options for cervical cancer. Here, we report a case of a 41-year-old patient who had a prior renal transplant and was diagnosed with early-stage, intermediate-risk adenocarcinoma treated with modified radical hysterectomy plus adjuvant proton-beam therapy and vaginal brachytherapy. Treatment was well tolerated with a disease-free interval of 14-months and preserved renal function.

To explore the application value of using 3-dimensional (3D) printing (3DP) technology to create individualized vaginal molds for brachytherapy (BT) in high-dose-rate 3D cervical cancer through reverse engineering of needle placement.

Prospectively, 11 patients with cervical cancer were treated with 3DP-intracavitary/interstitial (IC/IS) BT using 3DP to create individualized vaginal molds. All patients were performed BT after completion of external beam radiotherapy (EBRT). Each patient was treated with BT 5 times, the prescription dose was 600 cGy/F, which was performed once or twice a week, 2 of them were freehand IC/IS BT, and 3 were 3DP-IC/IS BT. The relevant planning parameters (bladder, rectum, sigmoid colon, and small intestine) and target conformity index (CI) for high-risk clinical target volume (HR-CTV) and organs at risk (OARs) were compared between the groups.

There were significant advantages in the 3DP-IC/IS BT group compared with the freehand IC/IS BT group: HR-CTV D90 (629.40±19.34 vs. 613.03±15.93 cGy, p=0.002), D95 (580.74±18.31 vs. 567.44±23.94 cGy, p=0.032), bladder D2cc (431.11±23.27 vs. 458.07±23.27 cGy, p<0.001), bladder D1cc and bladder D0.1cc. There was no statistically significant difference (p>0.05) between the 2 groups in rectal D2cc (352.30±42.42 vs. 361.29±42.42 cGy, p=0.470), sigmoid colon D2cc (236.73±78.95 vs. 246.50±58.17 cGy, p=0.621), CI (0.79±0.04 vs. 0.79±0.039 p=0.773), HR-CTV V100, V200, D98, D100 and other OARs parameters (p>0.05).

Compared with IC/IS BT, 3DP-IC/IS BT has apparent advantages with simple operation and high safety. In addition, individualized mold helps to improve the tumor target area's radiation dose while meeting the dose-limiting requirements for organs at risk and reduces the clinical proficiency requirements for operating physicians.

Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC.

Among most tailored approaches in radiation oncology, the development of brachytherapy for the treatment of cervical cancer patients has benefited from various technological innovations. The development of 3D image-guided treatments was the first step for treatment personalization. This breakthrough preceded practice homogenization and validation of predictive dose and volume parameters and prognostic factors. We review some of the most significant strategies that emerged from the ongoing research in order to increase personalization in uterovaginal brachytherapy. A better stratification based on patients and tumors characteristics may lead to better discriminate candidates for intensification or de-escalation strategies, in order to still improve patient outcome while minimizing the risk of treatment-related side effects.

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35.

Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group.

Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.

Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.

(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4-5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment.

Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25-75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8-6.0 months), 5.3 months (95% confidence interval: 4.5-6.3 months), and 3.0 months (95% confidence interval: 2.1-3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5-7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals.

Objective.To develop and evaluate a 3D Prompt-ResUNet module that utilized the prompt-based model combined with 3D nnUNet for rapid and consistent autosegmentation of high-risk clinical target volume (HRCTV) and organ at risk (OAR) in high-dose-rate brachytherapy for cervical cancer patients.Approach.We used 73 computed tomography scans and 62 magnetic resonance imaging scans from 135 (103 for training, 16 for validation, and 16 for testing) cervical cancer patients across two hospitals for HRCTV and OAR segmentation. A novel comparison of the deep learning neural networks 3D Prompt-ResUNet, nnUNet, and segment anything model-Med3D was applied for the segmentation. Evaluation was conducted in two parts: geometric and clinical assessments. Quantitative metrics included the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95%), Jaccard index (JI), and Matthews correlation coefficient (MCC). Clinical evaluation involved interobserver comparison, 4-grade expert scoring, and a double-blinded Turing test.Main results.The Prompt-ResUNet model performed most similarly to experienced radiation oncologists, outperforming less experienced ones. During testing, the DSC, HD95% (mm), JI, and MCC value (mean ± SD) for HRCTV were 0.92 ± 0.03, 2.91 ± 0.69, 0.85 ± 0.04, and 0.92 ± 0.02, respectively. For the bladder, these values were 0.93 ± 0.05, 3.07 ± 1.05, 0.87 ± 0.08, and 0.93 ± 0.05, respectively. For the rectum, they were 0.87 ± 0.03, 3.54 ± 1.46, 0.78 ± 0.05, and 0.87 ± 0.03, respectively. For the sigmoid, they were 0.76 ± 0.11, 7.54 ± 5.54, 0.63 ± 0.14, and 0.78 ± 0.09, respectively. The Prompt-ResUNet achieved a clinical viability score of at least 2 in all evaluation cases (100%) for both HRCTV and bladder and exceeded the 30% positive rate benchmark for all evaluated structures in the Turing test.Significance.The Prompt-ResUNet architecture demonstrated high consistency with ground truth in autosegmentation of HRCTV and OARs, reducing interobserver variability and shortening treatment times.

Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms.

The treatment of choice for patients with locally advanced cervical cancer (LACC) is definitive concurrent radio chemotherapy which consists of external beam radiotherapy (EBRT) and concurrent platinum-based chemotherapy (CCRT), with the possible addition of brachytherapy (BT). However, the benefits of adjuvant surgery after neoadjuvant treatments remain a debated issue and a still open question in the literature. This meta-analysis aims to provide an updated view on the controversial topic, focusing on comparing surgery after any adjuvant treatment and standard treatment.

Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, the PubMed and Embase databases were systematically searched in April 2023 for early publications. No limitations on the country were applied. Only English articles were considered. The comparative studies containing data about disease-free survival (DFS) and/or overall survival (OS) were included in the meta-analysis.

The CCRT + surgery group showed a significantly better DFS than CCRT (RR 0.69 [95% CI 0.58-0.81] p < 0.01) and a better OS (RR 0.70 [95% CI 0.55-0.89] p < 0.01). Nine studies comparing neoadjuvant chemotherapy (NACT) plus surgery and CCRT were also enrolled. The NACT + surgery group showed a significantly better DFS than CCRT (RR 0.66 [95% CI 0.45-0.97] p < 0.01) and a better OS (RR 0.56 [95% CI 0.38-0.83] p < 0.01). In the sub-analysis of three randomized control trials, the surgery group documented a non-significantly better DFS and OS than CCRT (OR 1.10 [95% CI 0.67-1.80] p = 0.72; I2 = 69% p = 0.72; OR 1.09 [95% CI 0.63-1.91] p = 0.75; I2 = 13% p = 0.32).

The results provide updated findings about the efficacy of neoadjuvant treatments, indicating significantly improved DFS and OS in patients undergoing hysterectomy after CCRT or NACT compared with patients undergoing standard treatments.

The incidence of cervical cancer in India is significantly high, and the average recurrence age is much less. The standard line of treatment consists of concurrent chemoradiotherapy. If a recurrence occurs, the treatment options or set of interventions are limited and suboptimal. Through this review, we have analyzed and classified the possible prognostic factors for cervical cancer into three broad categories, viz., (a) disease-related factors, (b) patient-related factors, and (c) treatment-related factors. Disease-related factors include tumor histology, tumor size, stage, parametrial involvement (PMI), Prognostic Nutritional Index (PNI), lymphovascular space invasion (LVSI), and nodal status. Patient-related factors include overall treatment time (OTT), nutritional status, hemoglobin level, comorbidities, and age. Treatment-related factors include addition of chemotherapy, techniques of external beam radiotherapy (EBRT), techniques of brachytherapy, and quality assurance for radiation therapy delivery. Out of these, extremely significant prognostic factors were tumor size and stage, nodal status, PMI, nutritional status, and addition of chemotherapy. Impactful factors include younger age, histology, LVSI, associated comorbidities, hemoglobin level, OTT, and patient-specific quality assurance. The factor that is not related or significant is the technique used for EBRT and brachytherapy delivery.

This study evaluated the first clinical implementation of daily iterative cone beam computed tomography (iCBCT)-guided online adaptive radiation therapy (oART) in the postoperative treatment of endometrial and cervical cancer.

Seventeen consecutive patients treated with daily iCBCT-guided oART were enrolled in this prospective study, with a reduced uniform 3-dimensional PTV margin of 5 mm. Treatment plans were designed to deliver 45 or 50.4 Gy in 1.8 Gy daily fractions to PTV. Pre- and posttreatment ultrasound and iCBCT scans were performed to record intrafractional bladder and rectal volume changes. The accuracy of contouring, oART procedure time, dosimetric outcomes, and acute toxicity were evaluated.

The average time from first iCBCT acquisition to completion of treatment was 22 minutes and 26 seconds. During this period, bladder volume increased by 44 cm3 using iCBCT contouring, whereas rectal volume remained stable (62.9 cm3 pretreatment vs 61.9 cm3 posttreatment). A total of 91.6% of influencers and 88.1% of CTVs required no or minor edits. The adapted plan was selected in all (434) fractions and significantly improved the dosimetry coverage for CTV and PTV, especially the vaginal PTV coverage by nearly 7% (P < .05). The adapted bladder Dmean was 104.61 cGy, and the rectum Dmean was 123.67 cGy, significantly lower than the scheduled plan of 108.24 and 128.19 cGy, respectively. The bone marrow and femur head left and right dosimetry were also improved with adaptation. Grade 2 acute gastrointestinal and genitourinary toxicities were 24% and 0, respectively. There was a grade 3 acute toxicity of decreased white blood cell count in 1 patient.

Daily oART was associated with favorable dosimetry improvement and low acute toxicity, supporting its safety and efficacy for postoperative treatment of endometrial and cervical cancer. These results need to be validated in a larger prospective randomized controlled cohort.

Objective.Active bone marrow (ABM) can serve as both an organ at risk and a target in external beam radiotherapy.18F-fluorothymidine (FLT) PET is the current gold standard for identifying proliferative ABM but it is not approved for human use, and PET scanners are not always available to radiotherapy clinics. Identifying ABM through other, more accessible imaging modalities will allow more patients to receive treatment specific to their ABM distribution. Multi-energy CT (MECT) and fat-fraction MRI (FFMRI) show promise in their ability to characterize bone marrow adiposity, but these methods require validation for identifying proliferative ABM.Approach.Six swine subjects were imaged using FFMRI, fast-kVp switching (FKS) MECT and sequential-scanning (SS) MECT to identify ABM volumes relative to FLT PET-derived ABM volumes. ABM was contoured on FLT PET images as the region within the bone marrow with a SUV above the mean. Bone marrow was then contoured on the FFMRI and MECT images, and thresholds were applied within these contours to determine which threshold produced the best agreement with the FLT PET determined ABM contour. Agreement between contours was measured using the Dice similarity coefficient (DSC).Main results.FFMRI produced the best estimate of the PET ABM contour. Compared to FLT PET ABM volumes, the FFMRI, SS MECT and FKS MECT ABM contours produced average peak DSC of 0.722 ± 0.080, 0.619 ± 0.070, and 0.464 ± 0.080, respectively. The ABM volume was overestimated by 40.51%, 97.63%, and 140.13% by FFMRI, SS MECT and FKS MECT, respectively.Significance.This study explored the ability of FFMRI and MECT to identify the proliferative relative to ABM defined by FLT PET. Of the methods investigated, FFMRI emerged as the most accurate approximation to FLT PET-derived active marrow contour, demonstrating superior performance by both DSC and volume comparison metrics. Both FFMRI and SS MECT show promise for providing patient-specific ABM treatments.

Recurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer  28-64  respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual sites and theirrecurrence pattern for unusual sites and its association with survival and prognosis.

To study overall survival in patients with distant metastasis compared to local and regional nodal metastasis.

A retrospective study was done from 1/1/2017 to 30/12/22. Cervical cancer patients post primary treatments were included. Survival was analyzed with respect to 3 groups local, regional nodalconducted from 1/1/2017 to 30/12/22. Cervical cancer patients who had received primary post-primary treatments were included. Survival was analyzed with respect to three groups: local, regional nodal, and distant metastasis.

225 patients had recurrences   post-completion of primary treatment, of which 105 (46.6%)(46.6 %) had local, 46 (20.4%)(20.4 %) had regional nodal, and 74 (33.3 %) had distant recurrences. The median time for recurrence in local, regional nodal, and atypical recurrences were 9, 9, and 13 months (p value - <0.05), respectively. Treatment included systemic chemotherapy 122 (54.2 %), metronomic therapy 19 (8.4 %), palliative radiotherapy 44 (19.5 %), palliative surgery 8 (3.5 %) and best supportive care 30 (13.3 %) patients. Median Time to treatment-death of patients after recurrence in local, nodal and distant recurrences was 17.0 months, 18.0 months and 10.0 months respectively (p value - < 0.05). Overall Survival of patients after primary treatment with local, nodal and distant recurrences was 35.0 months, 47.0 months and 50.0 months respectively (p value <0.05).

Local recurrence is most common, followed by regional, nodal, and distant recurrences. Overall survival post recurrence was lowest for distant recurrences and highest for local recurrences however overall survival after primary treatment completion was highest for distant recurrence due to the late presen; however, tation of distant recurrences.

A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis.

Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted.

A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions.

The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.

Shared decision making (SDM) is an approach where clinicians and patients make decisions together using the best available evidence. Although much studied, recognized to be ethically imperative, and recommended in international health policies, it remains poorly implemented. In the Philippines, there are limited studies on patient decision making preferences and SDM. Practical guidance on the implementation of SDM or use of patient decision aids (PtDAs) is often not detailed in existing national clinical practice guidelines in oncology.

We performed a systematic search of Philippine literature on SDM in oncology and an iterative review of international literature on the philosophy and methods of SDM, the utility and effectiveness of PtDAs, and the facilitators and barriers to implementation or usage. We contextualized our review to the cervical cancer management and health service delivery in the Philippines.

Local literature is limited to five scientific publications and two registered studies. International literature encompasses patient decisional preferences, the role of PtDAs and the standards for their development and evaluation, their effectiveness, and barriers and facilitators to their use in cancer-related decision making. We discussed the implications on the management of cervical cancer in the Philippines, challenges in health service delivery and standards, and SDM research.

Local SDM research is limited. Our preliminary experience in a multicenter clinical trial in Manila on PtDA use in the framework of SDM in cervical cancer suggest good patient and clinician acceptability. Challenges to implementation such as unfavorable financial situations, urgency of clinical decisions, low patient or caregiver educational attainment, and poor integration of multidisciplinary and SDM in organizational workflows will be important when implementing SDM in different settings.

Despite the evidence that photodynamic therapy (PDT) associated with chemotherapy presents great potential to overcome the limitations of monotherapy, little is known about the current status of this combination against cervical cancer. This systematic review aimed to address the currently available advances in combining PDT and chemotherapy in different research models and clinical trials of cervical cancer.

We conducted a systematic review based on PRISMA Statement and Open Science Framework review protocol using PubMed, Web of Science, Embase, Scopus, LILACS, and Cochrane databases. We selected original articles focusing on 'Uterine Cervical Neoplasms' and 'Photochemotherapy and Chemotherapy' published in the last 10 years. The risk of bias in the studies was assessed using the CONSORT and SYRCLE tools.

Twenty-three original articles were included, focusing on HeLa cells, derived from endocervical adenocarcinoma and on combinations of several chemotherapeutics. Most of the combinations used modern drug delivery systems for improved simultaneous delivery and presented promising results with increased cytotoxicity compared to monotherapy.

Despite the scarcity of animal studies and the absence of clinical studies, the combination of chemotherapy with PDT presents a potential option for cervical cancer therapy requiring additional studies.

https://doi.org/10.17605/OSF.IO/WPHN5 [Figure: see text].

High-throughput screening (HTS) platforms have been widely used to identify candidate anticancer drugs and drug-drug combinations; however, HTS-based identification of new drug-ionizing radiation (IR) combinations has rarely been reported. Herein, we developed an integrated approach including cell-based HTS and computational large-scale isobolographic analysis to accelerate the identification of radiosensitizing compounds acting strongly and more specifically on cancer cells.

In a 384-well plate format, 160 compounds likely to interfere with the cell response to radiation were screened on human glioblastoma (U251-MG) and cervix carcinoma (ME-180) cell lines, as well as on normal fibroblasts (CCD-19Lu). After drug exposure, cells were irradiated or not and short-term cell survival was assessed by high-throughput cell microscopy. Computational large-scale dose-response and isobolographic approach were used to identify promising synergistic drugs radiosensitizing cancer cells rather than normal cells. Synergy of a promising compound was confirmed on ME-180 cells by an independent 96-well assay protocol, and finally, by the gold-standard colony forming assay.

We retained 4 compounds synergistic at 2 isoeffects in U251-MG and ME-180 cell lines and 11 compounds synergistically effective in only one cancer cell line. Among these 15 promising radiosensitizers, 5 compounds showed limited toxicity combined or not with IR on normal fibroblasts.

Overall, this study demonstrated that HTS chemoradiation screening together with large-scale computational analysis is an efficient tool to identify synergistic drug-IR combinations, with concomitant assessment of unwanted toxicity on normal fibroblasts. It sparks expectations to accelerate the discovery of highly desired agents improving the therapeutic index of radiation therapy.

The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT).

This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively.

RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre.

The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.

Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer.

Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value.

Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR.

Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Several groundbreaking clinical trials with the potential to transform the management paradigm of both locally advanced and persistent, recurrent, or metastatic cervical cancers have been presented in 2023. This review describes the reported data from INTERLACE and KEYNOTE-A18 in the locally advanced setting, as well as BEATcc, innovaTV 301 and DESTINY-PanTumor02 for advanced disease. The practice implications of their positive results are interpreted in the context of global health considerations, and updated treatment algorithms are proposed. Furthermore, emerging trends in drug development for cervical cancer are discussed. As the routine use of immune checkpoint inhibitors (ICIs) for curative and palliative indications increases in the foreseeable future, patients whose cervical cancers which persist, relapse or progress after prior ICI exposure will represent an area of unmet clinical need and form the key target population for next-generation trials. Future research will help shape oncologists' approaches in the optimal selection, sequencing and re-treatment or rechallenge of immuno-oncology agents and/or antibody-drug conjugates in women with cervical cancer.

The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.

To assess efficacy outcomes in patient subgroups of KEYNOTE-826.

Exploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021.

Pembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 [area under the free carboplatin plasma concentration vs time curve]) with or without bevacizumab, 15 mg/kg.

Overall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1-positive tumors (defined as a combined positive score [CPS] ≥1) and in the intention-to-treat population.

A total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations.

The findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer.

ClinicalTrials.gov Identifier: NCT03635567.

Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification.

A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes.

Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry.

The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.

To compare the efficacy and safety of neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) vs. concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC) patients with large tumor masses.

LACC patients with localized tumor diameter >4 cm, were randomly allocated in an unblinded 1:1 ratio to NACT+CCRT or CCRT groups. Patients in the NACT+CCRT group were given paclitaxel combined with cisplatin (TP) NACT every 3 weeks for 2 cycles, followed by CCRT, with the chemotherapy regimen the same as for NACT. CCRT group were given CCRT with the same as for NACT.

From March 1, 2019, to June 30, 2021, 146 patients were included in the final analysis. Sixty-eight (93.2%) patients in the NACT+CCRT group and 66 (90.4%) patients in the CCRT group completed the expected treatment course. The complete response (CR) rate in the NACT+CCRT group was significantly higher than in the CCRT group (87.7% vs. 67.6%, χ²=54.540, p=0.000). In the NACT+CCRT group, the 1- and 2-year overall survival (OS) rates were significantly higher than those in the CCRT group (96% vs. 89% and 89% vs. 79%, χ²=5.737, p=0.017). Additionally, the rate of recurrences and distant metastases was significantly lower in the NACT+CCRT group than in the CCRT group (4.11% vs. 7.35%, χ²=4.059, p=0.021). Most treatment-related adverse events in both groups were grade 3.

Compared to CCRT, NACT+CCRT might improve the treatment completion rate, increase CR rate and 1- and 2-year OS rates, and reduce distant metastases rate for LACC patients with large tumor masses.

FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM1 (strongest hemopoietic ability region)and FBM2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer.

From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM1/2.