Fu-Quan Zhang

Different prognosis for stage IIB cervical cancer patients with unilateral or bilateral parametrial invasion treated with concurrent chemoradiotherapy

Abstract Objective To compare the survival difference between 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer (CC) patients with unilateral parametrial invasion (UL) and bilateral parametrial invasion (BL) disease, and explore the significant role of parametrial invasion (PI) in prognosis prediction. Methods A total of 506 stage IIB CC patients were identified from the multi-center study, and patients were divided into UL and BL groups according to gynecological and radiological examination. Survival outcomes were estimated and compared between 2 groups before and after propensity scoring matching (PSM). The role of upper 2/3 vaginal invasion (VI) in impacting survival probability was also assessed. The random forest (RF) model was constructed and validated to select important features related to survival outcomes and predict prognosis for these patients. The SHapley Additive exPlanation (SHAP) was further introduced to provide a better understanding toward the findings from the RF model. Results Significant better 5-year overall survival (OS) was observed among patients with UL disease whether before (BL: 61.7% [95% CI: 57.0%-66.4%]; UL: 84.8% [95% CI: 82.4%-87.2%]; HR = 2.83, 95% CI: 1.90-4.20, P < 0.001) or after PSM (BL: 61.3% [95% CI: 56.6%-66.0%]; UL: 81.2% [95% CI: 77.3%-85.1%]; HR = 2.51, 95% CI: 1.56-4.04, P < 0.001). Similar findings could also be observed in terms of progression-free survival (PFS). The presence of VI didn’t significantly impair the survival probability, whether in the UL or BL group (all P > 0.05). RF model was constructed, which possessed decent predictive ability both in the training (area under the receiver operating characteristic curve [AUC] = 0.893; 95% CI: 0.874-0.912) and validation cohort (AUC = 0.879; 95% CI: 0.801-0.957). PI was identified to be the paramount feature in affecting the survival outcomes for stage IIB CC patients through the Beeswarm summary plot and bar chart in SHAP analysis. Conclusion Our findings demonstrated that 2018 FIGO stage IIB CC patients with BL disease had a worse prognosis than those with UL disease, and PI was the most significant feature in prognosis prediction for these patients.

Moderately hypofractionated online adaptive radiotherapy (SWIFT-1) in cervical cancer patients: study protocol for a multi-centered, open-label, two-arm, phase III, randomized controlled study

External beam radiotherapy (EBRT) is an essential component of standard treatment for locally advanced cervical cancer. Moderately hypofractionated radiotherapy (MHRT) offers the potential to reduce treatment burden while compromising efficacy. Although various studies have investigated the safety and efficacy of MHRT, high-quality evidence remains inadequate. The lack of integration of modern radiotherapy techniques in many existing studies may lead to an overestimation of MHRT-associated toxicity. This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to evaluate the non-inferiority of moderately hypofractionated online adaptive radiotherapy (oART) compared to conventional fractionated radiotherapy (CFRT). A total of 440 participants will be enrolled and randomly assigned in a 1:1 ratio to either the MHRT or CFRT group. Both groups will receive concurrent chemoradiotherapy, and a subset of eligible patients will undergo immunotherapy. The prescribed EBRT dose for the MHRT group will be 43.35 Gy in 17 fractions, with a simultaneous integrated boost of 54.4 Gy in 17 fractions to positive lymph nodes. The CFRT group will receive 45 Gy in 25 fractions, with a simultaneous integrated boost of 60 Gy in 25 fractions to positive lymph nodes. The primary endpoint will be 3-year progression-free survival. Secondary endpoints will include the complete response rate, tumor regression following EBRT, overall survival, locoregional progression-free survival, metastasis-free survival, cervical cancer-specific survival, acute and late toxicity, and quality of life. This randomized controlled trial will prospectively investigate whether MHRT is non-inferior to conventional fractionation in terms of efficacy and safety. Furthermore, the trial will evaluate the potential of moderately hypofractionated oART as a clinically viable alternative to CFRT for the treatment of locally advanced cervical cancer. This trial was registered at ClincalTrials.gov (NCT06641635) on October 12, 2024.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography

Abstract Background Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. Methods This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. Results The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. Conclusions Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Higher Dose to Organs at Risk: The Unintended Consequences of Intravenous Contrast Use in Computed Tomography Simulation for Cervical Cancer

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). 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. 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. 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.

Segmentation of organs-at-risk in cervical cancer CT images with a convolutional neural network

We introduced and evaluated an end-to-end organs-at-risk (OARs) segmentation model that can provide accurate and consistent OARs segmentation results in much less time. We collected 105 patients' Computed Tomography (CT) scans that diagnosed locally advanced cervical cancer and treated with radiotherapy in one hospital. Seven organs, including the bladder, bone marrow, left femoral head, right femoral head, rectum, small intestine and spinal cord were defined as OARs. The annotated contours of the OARs previously delineated manually by the patient's radiotherapy oncologist and confirmed by the professional committee consisted of eight experienced oncologists before the radiotherapy were used as the ground truth masks. A multi-class segmentation model based on U-Net was designed to fulfil the OARs segmentation task. The Dice Similarity Coefficient (DSC) and 95th Hausdorff Distance (HD) are used as quantitative evaluation metrics to evaluate the proposed method. The mean DSC values of the proposed method are 0.924, 0.854, 0.906, 0.900, 0.791, 0.833 and 0.827 for the bladder, bone marrow, femoral head left, femoral head right, rectum, small intestine, and spinal cord, respectively. The mean HD values are 5.098, 1.993, 1.390, 1.435, 5.949, 5.281 and 3.269 for the above OARs respectively. Our proposed method can help reduce the inter-observer and intra-observer variability of manual OARs delineation and lessen oncologists' efforts. The experimental results demonstrate that our model outperforms the benchmark U-Net model and the oncologists' evaluations show that the segmentation results are highly acceptable to be used in radiation therapy planning.

A modified delineation method of para‐aortic nodal clinical target volume in patients with locally advanced cervical cancer

AbstractPurposeTo 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.MethodsA 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.ResultsWe 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).ConclusionCTV‐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.

Risk Factors for Nodal Failure in Patients with FIGO IIIC Cervical Cancer Receiving Definitive Image-Guided Radiotherapy

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.

Radiation- versus surgery-based treatment for patients with resectable IIIC1 cervical adenocarcinoma

To describe the utilization trend of radiation-based and surgery-based treatment in patients with resectable IIIC1 cervical adenocarcinoma and explore the optimal treatment strategy for these patients. Patients with resectable IIIC1 cervical adenocarcinoma in 2005-2022 from Surveillance, Epidemiology, and End Results program (SEER) were analyzed. Trends over time in the utilization of radiation- and surgery-based treatment were plotted and estimated using Mantel-Haenszel test. Logistic regression analysis was performed to identify factors associated with the utilization of treatment. Survival outcomes were assessed and compared using Kaplan-Meire method and log-rank test, respectively. Inverse probability of treatment weighting (IPTW) was performed for adjustment of baseline characteristics. Sensitivity analysis was conducted using a cohort of cervical adenocarcinoma patients from our institution. The utilization of radiation-based treatment has grown steadily from 2005 to 2022 while the trend for surgery-based treatment showed opposite way (P = 0.002). Age, year of diagnosed, tumor size and T stage impacted the utilization of radiation-based treatment (All P < 0.05). Surgery-based treatment demonstrated superior overall survival (HR = 0.55, 95%CI:0.44-0.69; P < 0.001) and cancer specific survival (HR = 0.58, 95%CI:0.45-0.75; P < 0.001) to radiation-based treatment before adjustment of IPTW. However, no significant differences were observed in overall survival (HR = 0.77, 95%CI:0.56-1.05; P = 0.1) and cancer specific survival (HR = 0.86, 95%CI:0.60-1.23; P = 0.4) after baseline characteristics were balanced. Besides, the cohort from our institution further verified that similar survival outcomes were observed between two treatment strategies. The utilization of radiation-based treatment has increased over time and showed non-inferior efficacy for patients with resectable IIIC1 cervical adenocarcinoma when compared to surgery-based treatment.

Moderated Hypofractionated Online Adaptive Radiotherapy in Cervical Cancer

The most common external beam radiotherapy fractionation scheme for cervical cancer is 45-50.4 Gy delivered in 25-28 fractions. However, prolonged treatment duration can lead to insufficient availability of medical resources. We hope to assess the safety and efficacy of moderated hypofractionated online adaptive radiotherapy in combination with brachytherapy in patients with cervical cancer in a multicenter study.