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Purpose To validate the nodal center coverage (NCC) of the three mainstream delineation methods of para‐aortic nodal clinical target volume (CTV) and propose a modified delineation method of para‐aortic nodal CTV in prophylactic extended‐field irradiation (EFI) of cervical cancer. Methods A total of 106 patients with para‐aortic lymph nodes (PALNs) identified on PET/CT were included at Peking Union Medical College Hospital between 2011 and 2020. PALNs were classified as left lateral para‐aortic (LLPA), aorto‐caval (AC), and right para‐caval (RPC). Distances from the nodal center to the aorta and inferior vena cava (IVC) were measured. The NCC of the three mainstream delineation methods of para‐aortic nodal CTV (CTV‐K, CTV‐S, and CTV‐D) and a modified CTV (CTV‐M) was calculated. Radiotherapy plans were created based on 4 CTVs for 10 selected patients who received prophylactic EFI. The chi‐squared test and the Student's t‐test were performed. Results We identified 344 PALNs (216 LLPA, 101 AC, and 27 RPC) in 106 patients. Mean distance from the nodal center to the aorta was 9.6 mm in the LLPA and 7 mm in the AC and from the nodal center to the IVC was 5.6 mm in the AC and 5.6 mm in the RPC. CTV‐D improved the NCC of 98% compared with 92% for CTV‐K (p = 0.002) and 95% for CTV‐S (p = 0.046). CTV‐M provided the same satisfactory NCC as CTV‐D (97% vs. 98%, p = 0.485). The V50Gy to the duodenum, the Dmean to the bilateral kidneys, and the V45Gy to the small bowel were significantly lower on the CTV‐M‐based plan than on the CTV‐D‐based plan (p = 0.001, 0.011, and 0.001, respectively). Conclusion CTV‐D provided more satisfactory NCC than CTV‐K and CTV‐S. CTV‐M provided the same satisfactory NCC as CTV‐D and reduced the dose to the critical structures., Our study is currently the largest data set in previous studies of anatomic distribution of fluorodeoxyglucose‐avid para‐aortic lymph nodes in cervical cancer. We validate nodal center coverage of the three mainstream delineation methods of para‐aortic nodal clinical target volume on our population and propose a modified delineation method to protect the critical structures.

Objective: Previous studies have shown that prophylactic extended-field irradiation can reduce para-aortic lymph node failure (PALNF) rates in patients with cervical cancer. As such, this type of irradiation may particularly benefit patients with a high risk of PALNF. In the present study, we analyzed the risk factors for PALNF in patients with cervical cancer treated with pelvic irradiation in order to identify potential indications of prophylactic extended-field irradiation. Methods: We evaluated patients with 2018 FIGO stage IB3-IIIC1 cervical cancer who were treated with definitive pelvic radiotherapy or concurrent chemoradiotherapy at our institution between 2011 and 2014. Univariate and multivariate analyses were performed to identify risk factors for PALNF. Results: We included 572 patients in the study. The median follow-up period was 37.9 months. Eighteen patients (3.1%) first site of tumor relapse was the para-aortic lymph nodes, and thus showed PALNF. Using multivariate Cox regression analysis, we identified two significant risk factors for PALNF: tumor extension to the pelvic wall (hazard ratio, HR 3.60, p=0.026) and ≥ 2 pelvic MLNs (HR 5.30, p=0.005). For patients with and without risk factors, the 3-year overall survival, disease-free survival, and PALNF rates were 77.3% and 90.1% (p

Purpose To validate the 2018 revised FIGO cervical cancer staging system for stage III patients with a cohort from China. Patients and Methods Patients with stage III cervical cancer (FIGO 2018) treated with definitive radiotherapy at our institute were reviewed. Each patient was evaluated with both the 2014 and 2018 staging systems. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Receiver operative characteristic (ROC) curves for the predictive accuracy of DFS in patients with cervical cancer according to different FIGO staging systems were created. Results Between January 2008 and December 2014, a total of 586 patients with FIGO stage IIIC cervical cancer (2018) were treated with definitive radiotherapy at our institute. The 3-year DFS for patients according to FIGO stage (2014) were as follows: IB2 73.2%, IIA 63.7%, IIB 66.7%, IIIA 64.7%, and IIIB 59.6% (P=0.580). The 3-year DFS according to FIGO stage (2018) were IIIA 79.9%, IIIB 70.4%, IIIC1 66.3% and IIIC2 29.8% (P

ObjectiveThis work aims to analyze the 100 most cited papers in radiotherapy or chemoradiotherapy for cervical cancer.MethodsThe 100 most cited papers in radiotherapy or chemoradiotherapy between 1990 and 2020 were identified with Thompson Reuters Web of Science citation indexing on August 24, 2020. The publication years, source titles, countries/regions, total citations, and average citations per year were extracted from the Web of Science. The research type and research domain were classified by the authors.ResultsThese 100 papers were cited a total of 28,714 times, and the median number of citations was 169.5 (ranging from 116 to 1,700 times). The most cited paper was “Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer” by Rose et al., with a total citation of 1,700 times. The International Journal of Radiation Oncology Biology Physics (40 papers), Radiotherapy and Oncology (14 papers), and the Journal of Clinical Oncology (12 papers) published the largest number of papers. USA (47 papers), Austria (18 papers), Canada (13 papers), and England (13 papers) contributed the largest number of papers. Image-guided adaptive brachytherapy (IGABT) had the largest number of papers (25 papers). Concurrent chemotherapy was the most cited research domain, with 10,663 total citations and 592.4 citations per paper.ConclusionIn the present study, we conducted a bibliometric analysis of the 100 most cited papers in radiotherapy or concurrent chemoradiotherapy for cervical cancer in the past 30 years. IGABT and concurrent chemotherapy were the most cited research domains.

Purpose: To evaluate the recurrent patterns and effect of clinicopathological factors on survival after recurrence (R-OS) in early stage endometrial cancer (EC). Methods: Patients with FIGO stage I-II EC, who underwent post-surgery radiotherapy (RT) at our institution between 2000 and 2017, were enrolled. First recurrent patterns, overall survival (OS), and R-OS were evaluated. Univariate and multivariate analyses (MVA) were used to evaluate factors associated with R-OS. Results: 756 patients were analyzed including 510 patients who received vaginal brachytherapy (VBT) and 246 patients who received external beam radiotherapy (EBRT) ± VBT, of whom 66 patients experienced recurrence, including 21 locoregional relapses and 45 distant metastases. Outside RT field recurrence predominated intra-RT field recurrence (106 versus 10 lesions). The 5-year OS rates for patients with and without recurrence were 62.2% and 98.2%, respectively (p

Purpose To compare the volumes of interest and doses to the organs at risk on contrast and noncontrast scans in patients with cervical cancer who underwent prophylactic extended-field radiation therapy (EFRT). Methods and Materials We reviewed twenty cervical cancer patients treated with prophylactic EFRT at Peking Union Medical College Hospital between March 2021 and April 2021. Each patient underwent noncontrast and contrast scans during simulation. All structures were contoured, and radiation therapy plans were created based on both scans. Student t test and Pearson correlation coefficient test were performed. Results Compared with the noncontrast scan, on the contrast scan, the mean volume of the inferior vena cava expanded by 44% (P ≤ .001), and the mean volume of the para-aortic nodal clinical target volume increased by 17% (P ≤ .001). For the second portion of the duodenum, the V30 (38.2% vs 43.8%, P = .038), V35 (27.6% vs 35.1%, P = .002), V40 (18.3% vs 26.3%, P = .014), V45 (11.2% vs 18.5%, P = .008), and V50 (4.2% vs 9.1%, P = .005) were significantly lower on the noncontrast scan than on the contrast scan. For the third portion of the duodenum, the V45 (78.4% vs 81.6%, P = .03) and V50 (59.7% vs 67%, P ≤ .001) were significantly lower on the noncontrast scan than on the contrast scan. For the right kidney, the V5, V10, V15, V20, and V25 on the contrast and noncontrast scans were 85.4% versus 79.8% (P = .013), 52.5% versus 45.6% (P = .021), 25.6% versus 20.1% (P = .003), 11.1% versus 7.5% (P = .001), and 3.8% versus 2.3% (P = .027), respectively. Conclusions Compared with the noncontrast scan, expansion of the inferior vena cava on the contrast scan can lead to excessive contouring and an overdose to the duodenum and right kidney in cervical cancer patients treated with prophylactic EFRT.

Currently, the standard radiation field for locally advanced cervical cancer patients without evidence of para-aortic lymph node (PALN) metastasis is the pelvis. Due to the low accuracy of imaging in the diagnosis of PALN metastasis and the high incidence of PALN failure after pelvic radiotherapy, prophylactic pelvic and para-aortic irradiation, also called extended-field irradiation (EFI), is performed for patients with cervical cancer. In the era of concurrent chemoradiotherapy, randomized controlled trials are limited, and whether patients with cervical cancer can benefit from prophylactic EFI is still controversial. With conformal or intensity-modulated radiation therapy, patients tolerate prophylactic EFI very well. The severe toxicities of prophylactic EFI are not significantly higher than those of pelvic radiotherapy. We recommend delivering prophylactic EFI to cervical cancer patients with common iliac lymph nodes metastasis. Clinical trials are needed to investigate whether patients with ≥3 positive pelvic lymph nodes and FIGO stage IIIB disease can benefit from prophylactic EFI. According to the distribution of PALNs, it is reasonable to use the renal vein as the upper border of the radiation therapy field for patients treated with prophylactic EFI. The clinical target volume expansion of the node from the vessel should be smaller in the right para-caval region than in the left lateral para-aortic region. The right para-caval region above L2 or L3 may be omitted from the PALN target volume to reduce the dose to the duodenum. More clinical trials on prophylactic EFI in cervical cancer are needed.

Purpose The purpose of the present study was to evaluate the role of the pre-treatment metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with locally advanced cervical cancer (LACC) treated with definitive concurrent chemoradiotherapy (CCRT) or radiotherapy. Methods Patients with LACC who underwent pre-treatment 18F-FDG PET/CT examination and definitive CCRT or radiotherapy between February 2010 and December 2015 in our institute were enrolled. For each patient, the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the primary tumour were measured. The survival outcomes were calculated with the Kaplan-Meier method. Cox proportional hazards models were used for univariate and multivariate analyses. Results A total of 125 patients were finally included in this study. The median follow-up duration was 62 months (range, 4-114 months). The 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and distant metastasis-free survival (DMFS) rates were 83.6%, 75.1%, 92.3% and 79.9%, respectively. Univariate analysis indicated that MTV ≥ 18.3 cm3 showed worse OS and DMFS; however, no significant differences were identified for OS and DMFS in multivariate analyses. TLG ≥ 113.4 implied worse DFS and DMFS. In multivariate analysis, TLG ≥ 113.4 was an independent predictive factor for OS, DFS and DMFS. SUVmax and SUVmean had no significant influence on OS, DFS, LC or DMFS in either univariate or multivariate analysis. Conclusion Pre-treatment TLG ≥ 113.4 was associated with a high incidence of disease recurrence and poor OS in patients with LACC.

Considering internal organ motion and tumor regression, it is controversial to use intensity-modulated radiation therapy (IMRT) in definitive radiotherapy for cervical cancer. In this study, we evaluated the efficacy and toxicity of IMRT combined with dose-escalated intracavitary brachytherapy (ICBT) for cervical cancer. In total, 373 consecutive FIGO-stage-IIB cervical cancer patients treated with IMRT combined with ICBT and concurrent chemotherapy were included in this study. A dose of 50.4 Gy in 28 fractions was delivered to the pelvis for IMRT. Weekly cone-beam computed tomography or daily megavoltage computed tomography was used for image guiding. For ICBT, 30-36 Gy in five to seven fractions were prescribed to point A. All patients received concurrent chemotherapy. The median follow-up duration was 32.5 months (range, 3.1-119.8 months). The three-year overall survival, disease-free survival and local control rates were 87.5%, 82.2% and 92.5%, respectively. Sixty patients (16.1%) experienced treatment failure, including 23 patients (6.2%) with pelvic relapse. The incidences of ≥grade 3 chronic gastrointestinal and genitourinary toxicity were 2.7% and 2.4%, respectively. These findings indicate that image-guided IMRT combined with dose-escalated ICBT results in good survival with acceptable toxicity in stage IIB cervical cancer patients.

Purpose To validate the 2018 revised FIGO cervical cancer staging system for stage III patients with a cohort from China. Patients and Methods Patients with stage III cervical cancer (FIGO 2018) treated with definitive radiotherapy at our institute were reviewed. Each patient was evaluated with both the 2014 and 2018 staging systems. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Receiver operative characteristic (ROC) curves for the predictive accuracy of DFS in patients with cervical cancer according to different FIGO staging systems were created. Results Between January 2008 and December 2014, a total of 586 patients with FIGO stage IIIC cervical cancer (2018) were treated with definitive radiotherapy at our institute. The 3-year DFS for patients according to FIGO stage (2014) were as follows: IB2 73.2%, IIA 63.7%, IIB 66.7%, IIIA 64.7%, and IIIB 59.6% (P=0.580). The 3-year DFS according to FIGO stage (2018) were IIIA 79.9%, IIIB 70.4%, IIIC1 66.3% and IIIC2 29.8% (P

Background The 3D structure and functions of ENPP4, a protein expressed on the surface of Bacillus Calmette–Guerin (BCG)-activated macrophages, are unknown. In this study, we analyzed the 3D structure of ENPP4 and determined its tumoricidal effects on MCA207 cells. Results Homology modeling showed that Arg305, Tyr341, Asn291, and Asn295 are important residues in substrate, adenosine triphosphate (ATP), binding. A molecular dynamics study was also carried out to study the stability of ENPP4 (including zinc atoms) as well as its ligand–enzyme complex. BCG increased ENPP4 expression in macrophages, and specific blocking of ENPP4 in BCG-activated macrophages (BAMs) significantly reduced their cytotoxicity against MCA207 cells. Conclusions These results indicate that zinc remains inside the ENPP4 protein, a BCG activated tumoricidal macrophage protein, throughout the simulation. Important information for the design of new inhibitors was obtained. Electronic supplementary material The online version of this article (doi:10.1186/s12944-016-0189-4) contains supplementary material, which is available to authorized users.