Jie Fu

The risk of radiation-associated second cancer in patients with cervical cancer following radiotherapy from 1975 to 2019

Abstract Background Radiation-associated second primary malignancies (SPMs) are a significant risk factor affecting the quality of life in long-term cervical cancer survivors. However, the impact of brachytherapy-boost and advanced radiotherapy techniques on the risk of radiation-related SPMs remains unclear. Methods We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2019) to assess the risk of radiation-associated SPMs among cervical cancer patients. Radiation-associated second solid and hematologic malignancies were defined as those diagnosed in survivors living for ≥5 and ≥2 years, respectively. The fine-gray sub-distribution hazard model was employed to compare the risk of SPMs across different groups. Results External beam radiation therapy (EBRT) was associated with an increased risk of pelvic SPMs (sub-distribution hazard ratio [sHR] = 2.13; P < .001). However, no increased risk was observed for extra-pelvic or hematologic SPMs. For radiotherapy-treated patients, the 15-year cumulative incidence of overall pelvic SPMs significantly declined from 3.92% in 1975-1994 to 2.85% in 1995-2006 (sHR = 0.87; P = .036), further decreasing to 2.27% after 2001 compared to those treated in 1975-2001 (sHR = 0.59; P = .030). Brachytherapy alone increased the risk of pelvic SPMs (sHR = 3.04; P < .001), but the combination of brachytherapy with EBRT did not further elevate the risk of pelvic SPMs (sHR = 1.35; P = .092). Conclusions The risk of radiation-associated pelvic SPMs has diminished over the past 40 years, and the combination of brachytherapy with EBRT did not further increase the risk of SPMs among cervical cancer patients.

Perineural invasion in cervical cancer

Perineural invasion (PNI), the neoplastic infiltration of peripheral nerves, is recognized as the fourth mode of tumor metastasis and invasion. PNI is defined as a critical pathological feature observed across various cancers and is associated with poor prognosis. Recent studies have demonstrated that PNI also occurs in cervical cancer. Nerve-sparing radical hysterectomy (NSRH) has been promoted as the preferred approach for radical surgical resection of cervical cancer, as it reduces postoperative complications such as bladder, rectal, and sexual dysfunction. However, the presence of PNI has become a contraindication for NSRH. Despite the increasing volume of studies on PNI, the underlying mechanisms of its pathogenesis remain largely unclear. In this review, we discuss the innervation, characteristics, preoperative prediction and diagnosis of PNI in cervical cancer, along with its underlying mechanism, paving the way for advancements in treatment strategies and improving the prognosis for cervical cancer patients.

The role of radiomics for predicting of lymph-vascular space invasion in cervical cancer patients based on artificial intelligence: a systematic review and meta-analysis

The primary aim of this study was to conduct a methodical examination and assessment of the prognostic efficacy exhibited by magnetic resonance imaging (MRI)-derived radiomic models concerning the preoperative prediction of lymph-vascular space infiltration (LVSI) in cervical cancer cases. A comprehensive and thorough exploration of pertinent academic literature was undertaken by two investigators, employing the resources of the Embase, PubMed, Web of Science, and Cochrane Library databases. The scope of this research was bounded by a publication cutoff date of May 15, 2023. The inclusion criteria encompassed studies that utilized radiomic models based on MRI to prognosticate the accuracy of preoperative LVSI estimation in instances of cervical cancer. The Diagnostic Accuracy Studies-2 framework and the Radiomic Quality Score metric were employed. This investigation included nine distinct research studies, enrolling a total of 1,406 patients. The diagnostic performance metrics of MRI-based radiomic models in the prediction of preoperative LVSI among cervical cancer patients were determined as follows: sensitivity of 83% (95% confidence interval [CI]=77%-87%), specificity of 74% (95% CI=69%-79%), and a corresponding AUC of summary receiver operating characteristic measuring 0.86 (95% CI=0.82-0.88). The results of the synthesized meta-analysis did not reveal substantial heterogeneity.This meta-analysis suggests the robust diagnostic proficiency of the MRI-based radiomic model in the prognostication of preoperative LVSI within the cohort of cervical cancer patients. In the future, radiomics holds the potential to emerge as a widely applicable noninvasive modality for the early detection of LVSI in the context of cervical cancer.

Less than whole uterus irradiation for patients with locally advanced cervical cancer

Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation. We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point. The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups. Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

A comparison of concurrent chemoradiotherapy and radical surgery in patients with specific locally advanced cervical cancer (stage IB3, IIA2, IIICr): trial protocol for a randomized controlled study (C-CRAL trial)

At present, clinical dilemma remains to be solved in terms of therapy-choices for specific locally advanced cervical cancer (LACC) patients: 1) Although concurrent chemoradiotherapy (CCRT) is recommended as the first choice for them, many patients, influenced by the Chinese culture, prefer to choose radical surgery (RS) as their primary treatment. The difference between the 2 therapies in improving patient prognosis is still unknown. 2) Laparoscopy has been questioned since the noted Laparoscopic Approach to Cervical Cancer trial. Nevertheless, clinical research on laparoscopic surgery under the strict tumor-free principle is still underway globally, therefore whether laparoscopic surgery can be used for specific LACC is also an urgent issue to be explored. A multi-center, randomized controlled study is designed to investigate the effect of different treatment strategies on the prognosis and quality of life (QoL) in patients with specific locally LACC. A total of 402 patients will be enrolled over a period of 3 years. Eligible patients will be randomized (3:1) to either RS group or CCRT group. Patients assigned to RS group will be randomized (1:2) to the abdominal RS group or laparoscopic RS group. All patients will then be followed-up for 5 years. The primary end point is the 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events caused by RS or CCRT and QoL. Chinese Clinical Trial Registry Identifier: ChiCTR2000041315.

Predictive significance of lymphocyte level and neutrophil‐to‐lymphocyte ratio values during radiotherapy in cervical cancer treatment

AbstractObjectiveThe objective of this research was to analyze the prognostic significance of the minimum count of lymphocytes (LY) and the corresponding ratio of neutrophil‐to‐lymphocyte (NLR) in cervical cancer (CC) patients receiving radiotherapy.MethodsWe retrospectively collected data from 202 CC patients who received concurrent chemoradiotherapy or radiotherapy alone at our hospital. Statistical methods including the Kaplan–Meier method, log‐rank test and the Cox proportional hazards model were included to examine survival differences and identify independent factors that may affect overall survival (OS) and progression‐free survival (PFS).ResultsThe research enrolled a total of 202 patients. Patients with higher LY levels and lower NLR values during radiotherapy had significantly better survival prognosis than those with lower LY levels and higher NLR values. Multivariate COX regression analysis revealed that FIGO stage I, pathological types of SqCC, absence of lymph node metastasis, concurrent chemoradiotherapy, higher LY levels during radiotherapy, and lower NLR values before radiotherapy were independently associated with poorer PFS. Similarly, FIGO stage I, absence of lymph node metastasis and lower NLR values during and before radiotherapy were independently linked with poorer OS.ConclusionMinimum LY value and its corresponding NLR during radiotherapy serve as prognostic factors for CC.