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Background: Nodal failure is a major failure pattern for patients with FIGO IIIC cervical cancer, which is further associated with worse survival. This study was designed to investigate risk factors for nodal failure in FIGO IIIC cervical cancer patients. Methods: The characteristics of positive lymph nodes (LNs) and relevant clinical factors of 162 FIGO IIIC cervical cancer patients were collected. The chi-square test and logistic regression model were used to identify risk factors for nodal failure. Results: In total, 368 positive LNs were identified, including 307 pelvic LNs and 61 para-aortic LNs. The nodal failure rates for all LNs, pelvic LNs, and para-aortic LNs were 9.2%, 7.8%, and 16.4%, respectively. After 20 fractions of RT, a nodal short diameter (D20F) ≥ 0.95 cm and a ratio of nodal shrinkage (ΔV20F) < 0.435 resulted; <4 cycles of chemotherapy indicated higher nodal failure rates for all LNs. For pelvic LNs, ΔV20F < 0.435 and <4 cycles of chemotherapy were associated with a higher incidence of nodal failure. For para-aortic LNs, ΔV20F < 0.435 was the only risk factor for nodal failure. Conclusions: Para-aortic LNs were more likely to experience nodal failure than pelvic LNs. Nodal shrinkage during radiotherapy and cycles of chemotherapy were associated with nodal failure in patients with FIGO IIIC cervical cancer. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is the most common type of vaginal recurrence in cervical cancer patients, and the role of salvage radiotherapy on these patients remains unclear. This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of SCC in patients who previously underwent surgery and to explore prognostic factors associated with survival. Ninety-seven patients with histologically proven SCC who were treated for vaginal recurrence at Peking Union Medical College Hospital were identified. All patients had previously undergone surgery and received salvage radiotherapy. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated. The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%. On multivariate analysis, inguinal lymph node metastasis was significantly associated with poor OS; a tumour size ≤4 cm was associated with longer PFS (p < 0.05); the recurrence pattern was an independent predictor of LC (p < 0.05). In the 45 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥72.6 Gy were independently predictive of longer LC (p < 0.05). RT is an effective treatment for postoperative vaginal recurrence in patients with cervical SCC. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal. What is already known on this subject? Radiotherapy plays a critical role in treating recurrent cervical cancer, but the effectiveness of RT for vaginal recurrence in patients who previously underwent surgery remains limited. Few studies have focussed on the effect of RT dose on patient survival. What do the results of this study add? This study investigated the efficacy of RT in patients with cervical squamous cell carcinoma who experienced postoperative recurrence. Lymph node metastasis, tumour size and recurrence pattern were significantly associated with survival. Moreover, an EQD2 ≥ 72.6 Gy was independently predictive of longer LC. What are the implications of these findings for clinical practice and/or further research? RT is an effective treatment for postoperative vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal. [ABSTRACT FROM AUTHOR]

Objective: The role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence. Methods: Patients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated. Results: A total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670). Conclusions: RT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors. [ABSTRACT FROM AUTHOR]

Background: The new staging system of cervical cancer issued in 2018 by the International Federation of Gynecology and Obstetrics (FIGO), calls for a new evaluation of the efficacy of prophylactic extended field irradiation (EFI) in the concomitant chemoradiotherapy/brachytherapy treatment of locally advanced cervical cancer patients (stage IIIB).Methods: We performed a retrospective study consisting of 133 FIGO IIIB cervical cancer patients treated in the Peking Union Medical College Hospital from 2002 to 2010. The patients were distributed in two groups depending whether they were treated with EFI or pelvic only irradiation. The therapeutic efficacy, toxicity and prognostic factors of EFI were evaluated in the frame of the new FIGO staging system.Results: When compared to patients who received pelvic only irradiation, patients who received prophylactic EFI showed significantly less distant metastasis and a significant improvement in their 5 years overall survival (OS), disease free survival (DFS), out of field recurrence free survival (OFRFS) and para-aortic lymph node metastasis free survival (PALNMFS). Multivariate analysis revealed that EFI is an independent prognosis factor for DFS, OFRFS and PALNMFS. Finally, although more acute complications were observed in the EFI group, there is no significantly worst acute toxicity in the EFI group.Conclusion: Our retrospective analysis supports the prophylactic effect of EFI in the concomitant chemoradiotherapy treatment of IIIB patients and suggests that this prophylactic effect is associated with a clear improvement in 5-years OS, DFS, OFRFS and PALNMFS. Consequently, EFI appears to be a very valid treatment option for FIGO IIIB cervical cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for oligometastatic pulmonary tumors from cervical cancer. Methods: A total of 29 oligometastatic pulmonary lesions from cervical cancer in 19 patients were treated with SBRT in our institute from 2011 to 2016. Thirteen patients (68.4%) suffered with solitary lung metastasis, three patients (15.8%) with multiple unilateral lesions and three patients (15.8%) with bilateral lesions. The median size of lung lesions was 2 cm (0.7–5.6 cm). Patients underwent cone‐beam CT before the delivery of SBRT. The most common dose fractionation schemes were 64 Gy in eight fractions (eight lesions) and 56 Gy in seven fractions (seven lesions). Nine patients (47.4%) received systemic chemotherapy. Results: The median follow‐up was 9.5 months (3.0–62.4 months). The one‐year overall survival (OS), progression‐free survival (PFS) and local control (LC) rates were 76.8%, 55.8% and 75.6%, respectively. The median PFS was 12.7 months. Six patients (31.6%) gained more than 20 months disease‐free survival. Eleven patients (57.9%) experienced tumor relapse, including seven patients with pulmonary relapse and four patients with extra‐pulmonary disease. Only one patient (5.3%) experienced symptomatic radiation pneumonitis (grade 2). Conclusion: SBRT was an efficacy and safe approach for patients with oligometastatic pulmonary tumor from cervical cancer. SBRT should be considered as a potential alternative to resection for these patients. [ABSTRACT FROM AUTHOR]

Intracavitary and/or interstitial brachytherapy is an integral component of the management of patients with central pelvic-recurrent cervical cancer after primary hysterectomy, and is typically delivered using conventional applicators. We investigated the efficacy and safety of three-dimensional (3D)-printed, customizable applicators for those patients. Twenty-six patients were treated with combination external beam radiotherapy and brachytherapy. Patients with lesions ≤1 and >1 cm before brachytherapy were treated with intracavitary and interstitial brachytherapy, respectively. Dosimetric plans were compared between the vaginal cylinder and 3D-printed applicator for the first 9 patients. Outcomes and treatment-related complications were also investigated. The median tumor size before brachytherapy was 0.81 cm. Intracavitary, interstitial, and combined interstitial-intracavitary brachytherapy were performed in 22 (85%), 3 (11%), and 1 (4%) of the patients, respectively. The clinical target volume (CTV) coverage goal was achieved with all 3D-printed plans but failed with three single-channel cylinder plans (33.3%). Owing to 3D-printed transvaginal applicator guidance, there was no need to adjust the needle position after implantation. The mean CTV dose for all patients was 71 ± 8.2 Gy; all met the dose constraints to the organs at risk, but 1 (4%) had a rectal D 2cc overdose. The 2-year local control, progression-free survival, and overall survival rates were 87.8%, 71.0%, and 91.6%, respectively. Four patients (21%) developed early grade 3–4 hematological toxicities and 1 (4%) developed a late grade 3 adverse event. High-quality intracavitary and/or interstitial brachytherapy can be achieved using a 3D-printed applicator and yields favorable outcomes with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for pulmonary metastases from cervical cancer. Methods: Nineteen patients with 29 oligometastatic pulmonary lesions form cervical cancer were treated with SBRT in our institute from July 2011 to July 2016. Before pulmonary metastases, all patients experienced a period of disease free survival after initial treatment. Thirteen patients (68.4%) suffered with solitary lung metastasis, 3 patients (15.8%) with multiple unilateral lesions and 3 patients (15.8%) with bilateral lesions. The median size of lung lesions was 2cm (0.7- 5.6cm). Patients underwent cone-beam CT before the delivery of SBRT. The most common dose fractionation schemes were 64Gy in 8 fractions (8 lesions) and 56Gy in 7 fractions (7 lesions). Nine patients (47.4%) received systemic chemotherapy. Results: The median follow-up was 9.5 months (3.0-62.4months). The median follow-up of survival patients was 18.9 months (3.6-62.4months). The 1-year overall survival (OS), progression free survival (PFS), regional control (RC) and local control (LC) were 76.8%, 55.8%, 68.1% and 75.6%, respectively. The median OS and PFS were 62.4 and 12.7 months, respectively. Six patients (31.6%) gained more than 20 months disease-free survival. Eleven patients (57.9%) experienced tumor relapse, including 7 patients with pulmonary relapse and 4 patients with extra-pulmonary disease. Only 1 patient (5.3%) suffered with symptomatic radiation pneumonitis (grade 2). Conclusion: SBRT was an efficacy treatment approach with low toxicity for oligometastatic pulmonary disease from cervical cancer. It should be considered as an important approach for pulmonary disease from cervical cancer beside surgery. [ABSTRACT FROM AUTHOR]

To analyze the association between posttreatment squamous cell carcinoma antigen (SCC Ag) and treatment failure in patients with cervical SCC treated with concurrent chemoradiotherapy (CCRT). We reviewed patients with cervical SCC who were treated with definitive radiotherapy or CCRT between June 2012 and May 2015 at our institute. A receiver operating characteristic (ROC) curve was used to analyze the cutoff value of posttreatment SCC Ag in predicting treatment failure. Log-rank tests and Cox proportional hazards models were used to identify whether posttreatment SCC Ag was significant in predicting disease-free survival (DFS). A total of 559 patients were included in this study. With the ROC curve, the optimal cutoff posttreatment SCC Ag level was 1.8 ng/mL (sensitivity 27.1%, specificity 96.6%). A posttreatment SCC Ag level ≥ 1.8 ng/mL was observed in 47 patients. The multivariate analysis showed that posttreatment SCC Ag (hazard ratio 5.10; 95% confidence interval, 3.31–7.88; p < 0.001) was an independent prognostic factor of DFS. The 3-year overall survival (OS), DFS, local control, and distant control rates of patients with posttreatment SCC Ag < 1.8 ng/mL and ≥1.8 ng/mL were 90.7% and 46.4% (p < 0.001), 84.8% and 31.9% (p < 0.001), 81.4% and 69.5% (p < 0.001), and 90.4% and 54.1% (p < 0.001), respectively. Patients with posttreatment SCC Ag ≥ 1.8 ng/mL suffer due to a high rate of treatment failure and poor survival. • Posttreatment SCC Ag could predict tumor relapse after CCRT for patients with cervical cancer. • The 3-year DFS of patients with posttreatment SCC Ag ≥ 1.8 ng/mL was just 31.9%. • Consolidation therapy or extensive follow-up should be considered for these patients. [ABSTRACT FROM AUTHOR]

Abstract Objective Image guidance should be used for patients with cervical cancer treated with definitive intensity-modulated radiation therapy (IMRT). In this study, we provided a pattern of image guidance and verified it in a large population. Methods We retrospectively analyzed patients with stages IB1–IVA cervical cancer treated with IMRT combined with high-dose brachytherapy and concurrent chemotherapy in our institute from January 2005 to December 2015. A dose of 50.4 Gy in 28 fractions was prescribed to the planning target volume with fixed-field IMRT, volumetric modulated arc therapy, or helical tomotherapy. Daily megavoltage computed tomography (CT) or weekly cone-beam CT (CBCT)/CT-on-rail were used for image guidance. Considering tumor regression during treatment, a second CT simulation and IMRT planning after 20 fractions of IMRT was performed. Results A total of 1433 patients were included in this study. Four hundred thirteen patients (28.8%) had regional lymph node metastases. A total of 1261 patients (88.0%) received concurrent chemotherapy. The median follow-up was 32.2 months (range, 1.9–124.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates were 83.0%, 75.0%, and 87.4%, respectively. The 3-year DFS rates for patients with stages IB1, IB2, IIA, IIB, IIIA, IIIB, and IVA disease were 90.2%, 87.6%, 84.0%, 76.7%, 61.6%, 59.8%, and 25.9%. The incidence rates of grade 3 or greater chronic gastrointestinal and genitourinary toxicities were 2.3% and 1.3%. Conclusion This pattern of image guidance was rational for patients with cervical cancer treated with IMRT. The survival rates were high, and the toxicities were acceptable. Highlights • We provided a pattern of image guidance for patients with cervical cancer treated with IMRT. • Daily MVCT or weekly CBCT/CT-on-rail were used for image guidance. • A second CT simulation and IMRT planning after 20 fractions of IMRT was performed. • Image-guided IMRT resulted in high survival rates and acceptable toxicities. [ABSTRACT FROM AUTHOR]