Does para-aortic irradiation reduce the risk of distant metastasis in advanced cervical cancer? A systematic review and meta-analysis of randomized clinical trials

Abstract

Purpose To evaluate the impact of the extension of the radiotherapy field cranially toward para-aortic lymph nodes (EF-RT) in advanced cervical cancer. Materials and Methods A systematic search of databases (PubMed, CENTRAL, Clinical Trials) was performed and included studies that were published between 1960 and November 2015 without language restrictions. All randomized clinical trials (RCTs) were analyzed further. All patients must have undergone pelvic radiotherapy and the same systemic therapy in both arms. The primary endpoints were locoregional failure, incidence of distant metastasis, para-aortic failure, and cancer related death. The Mantel-Haenszel method was used in the meta-analysis. The risk of bias analysis was determined using the 7-domain method per the Cochrane Handbook for Systematic Reviews of Interventions V5.1.0. A review of the treatment technique and toxicity was also performed. Results A total of 1309 studies were evaluated, 4 RCTs of which met the inclusion criteria; 506 patients were allocated to standard pelvic irradiation, and 494 underwent EF-RT. The risk of bias was considered to be low in nearly 80% of the domains. EF-RT significantly reduced the rate of para-aortic failure (HR 0.35, 95% CI 0.19–0.64; p<0.01) and the incidence of other distant metastases (HR 0.69, 95% CI 0.50–0.96; p=0.03). Locoregional failure and cancer-related death were not significantly altered (OR 1.06 [0.80–1.42]; p=0.67, and 0.68 [0.45–1.01]; p=0.06, respectively). The radiotherapy technique was conventional in 3 studies and conformational in 1 study. In total, 10 treatment-related deaths occurred—4 in pelvic radiation and 6 in EF-RT (OR 2.12 [0.71–6.27]; p=0.18). Conclusions EF-RT that targets the para-aortic lymphatic chain reduces distant metastatic events, but its impact on survival is unknown. Future studies should examine the value of EF-RT using modern radiation techniques.

Prophylactic extended-field irradiation with concurrent chemotherapy for pelvic lymph node-positive cervical cancer

“…Our findings are consistent with those of Park et al [ 25 ] and Yap et al [ 26 ]. A recent meta-analysis regarding EF-PRT by Sapienza et al [ 29 ] reported that cancer-related death was not significantly altered (odds ratio, 0.68; CI, 0.45–1.01; p = 0.06), and the potential impact of PALN RT on survival warrants a reconsideration of EF-PRT. Collectively, these results of the present and previous studies indicate that the clinical benefit of EF-PRT with concurrent chemotherapy was limited.…”

The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: Early results from a phase III randomised controlled trial

“…Para-aortic nodes seen on PET/CT images were therefore not targeted with EBRT. While extended fields to include para-aortic nodes significantly decreases the risk of distant metastases and of para-aortic failure, the effects on overall survival are not yet confirmed[57] and extended fields are not standard in a resource-constrained setting such as ours.…”

Skeletal Muscle Loss Is an Imaging Biomarker of Outcome after Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer

“…Therefore, CT images are easily available for measuring body composition change during treatment, and hence, can be used as potential imaging biomarkers to predict outcomes in clinical practice (6,26). Previous studies on the prognosis of LACC (27)(28)(29)(30)(31)(32) have mainly focused on tumor-specific or treatmentrelated factors, such as International Federation of Gynecology and Obstetrics (FIGO) stage, nodal status, pathology, chemotherapy, and radiation field. However, the effect of body composition change during treatment remains unclear in patients with LACC.…”