Clinical outcomes of pelvic bone marrow sparing radiotherapy for cervical cancer: A systematic review and meta-analysis of randomised controlled trials.

Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes. Methods: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis. Results: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes. Conclusions: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

Dose-volume metric-based prediction of radiotherapy-induced lymphocyte loss in patients with non-small-cell lung cancer treated with modern radiotherapy techniques.

Background and Purpose: Radiation-induced lymphopenia (RIL) is a common side effect of radiotherapy (RT) that may negatively impact survival. We aimed to identify RIL predictors in patients with non-small-cell lung cancer (NSCLC) treated intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Materials and Methods: We retrospectively analysed data of 306 patients who underwent radical RT for NSCLC. Absolute lymphocyte count (ALC) loss was evaluated for each patient by fitting an exponential decay curve to data from first 45 days since treatment start, and percentage ALC loss relative to baseline was calculated based on area under the decay curve and baseline ALC. We compared IMRT and VMAT treatment plans and used linear regression to predict ALC loss. Results: ALC decreased during RT in the whole patient group, while neutrophil counts remained stable and decreased only in those treated with concurrent chemoradiotherapy (CRT). Percentage ALC loss ranged between 11 and 78 % and was more strongly than lymphocyte nadir correlated with dose-volume metrics for relevant normal structures. We found evidence for the association of high radiation dose to the lungs, heart and body with percentage ALC loss, with lung volume exposed to 20-30 Gy being most important predictors in patients treated with IMRT. A multivariable model based on CRT use, baseline ALC and first principal component (PC1) of the dose-volume predictors showed good predictive performance (bias-corrected R2 of 0.40). Conclusion: Percentage lymphocyte loss is a robust measure of RIL that is predicted by baseline ALC, CRT use and dose-volume parameters to the lungs, heart and body.

The Prognostic Value of the Systemic Immune-Inflammation Index (SII) and Red Cell Distribution Width (RDW) in Patients with Cervical Cancer Treated Using Radiotherapy.

INTRODUCTION: There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and OS in patients treated with radiotherapy for primary localised cervical cancer. MATERIAL AND METHODS: This retrospective analysis included patients treated with definitive CRT between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan-Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the AIC serving as a prediction error estimator. RESULTS: The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237; 95.2%) and had FIGO stage III (211; 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p = 0.001 and p = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32-3.16; p = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15. CONCLUSIONS: The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation.

Volumetric staging in radiotherapy for oropharyngeal cancers.

INTRODUCTION: Despite routine use of 3D radiotherapy planning in radical radio(chemo)therapy for oropharyngeal cancers, volumetric data have not been implemented in initial staging. We analyzed 228 oropharyngeal cancer cases treated at one institution between 2004 and 2014 to compare the predictive value of volumetric staging and tumor nodal metastasis staging system (TNM) and determine whether they could be complementary for the estimation of survival. METHODS: This retrospective study analyzed 228 consecutive oropharyngeal cancer cases treated with radiotherapy (76.9%) or concurrent radiochemotherapy (23.1%) between 2004 and 2014. The volumetric parameters included primary gross tumor volume (pGTV), metastatic lymph nodes gross tumor volume (nGTV), and total gross tumor volume (tGTV), and were compared with the 7th edition of the TNM staging system. RESULTS: Median overall survival (OS) was 30.3 months. In the receiver operating characteristic analysis, tGTV had the highest area under the curve (AUC) of 0.66, followed by pGTV (AUC,0.64), nGTV (AUC 0.62), and TNM (AUC 0.6). The median OS for patients with tGTV ⩽32.2 mL was 40.5 months, compared to 15.4 months for >32.2 mL (p < 0.001). This threshold allowed for a statistically significant difference in survival between TNM stage IV cases with low and high tumor volume (p < 0.001). Despite both TNM and tGTV reaching statistical significance in univariate analysis, only the tGTV remained an independent prognostic factor in the multivariate analysis (hazard ratio 1.07, confidence interval 1.02-1.12, p = 0.008). CONCLUSIONS: tGTV is an independent prognostic factor, characterized by a higher discriminatory value than the TNM staging system, and can be used to further divide stage IV cases into subgroups with significantly different prognosis.

The prognostic value of red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in radiotherapy for oropharyngeal cancer.

BACKGROUND: Red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are known inflammatory indices. Elevated values are found in many cancers and may be associated with a poor prognosis. The article aimed to assess the impact of RDW, NLR, and PLR on overall survival (OS) of patients with oropharyngeal cancer treated with radiotherapy (RT). MATERIALS AND METHODS: This retrospective study includes 208 patients treated for oropharyngeal cancer with definitive RT or RT combined with neoadjuvant or concurrent systemic therapy, at one institution between 2004 and 2014. The receiver operating characteristic (ROC) method, log-rank testing, and Cox proportional hazards regression model were used for the analysis. RESULTS: The OS was significantly higher in RDW ≤ 13.8% (p = 0.001) and NLR ≤ 2.099 (p = 0.016) groups. The RDW index was characterized by the highest discriminatory ability [area under the curve (AUC) = 0.59, 95% confidence interval (CI): 0.51-0.67], closely followed by NLR (AUC = 0.58, 95% CI: 0.50-0.65). In the univariate Cox regression analysis, RDW [hazard ratio (HR): 1.28, 95% CI: 1.12-1.47, p < 0.001] and NLR (HR: 1.11, 95% CI: 1.06-1.18, p < 0.001) were associated with an increased risk of death. In the multivariate analysis, among the analyzed indices, only NLR was significantly associated with survival (HR: 1.16, 95% CI: 1.03-1.29, p = 0.012). CONCLUSIONS: In the study, only NLR proved to be an independent predictor of OS. However, its clinical value is limited due to the relatively low sensitivity and specificity.