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Objective: The objective of this study was to assess the prognostic value of clinical factors and metabolic parameters measured using fluorodeoxyglucose PET (FDG-PET/CT) in predicting disease recurrence, as well as distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and overall survival (OS) in patients with uterine cervical cancer who received definitive chemoradiotherapy., Methods: The clinical data and FDG-PET parameters, including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 194 patients with biopsy-confirmed squamous cell carcinoma of cervical cancer were retrospectively analyzed. Univariate and multivariate analyses were used to ascertain prognostic factors associated with DMFS, LRFS, and OS., Results: With a median follow-up of 12.5 years, 96 patients (49.5%) presented with disease recurrence, at a median of 9.9 months after chemoradiotherapy. Patients who experienced recurrence had significantly higher values for all FDG-PET parameters compared to patients who did not. In multivariate regression analysis, lymph node metastasis, MTV, and SUV mean were significantly correlated with distant metastasis, while local recurrence was only predicted by SUV max . Lymph node metastasis, high MTV, SUV mean , and TLG predicted shorter DMFS, while only the primary tumor SUV max predicted LRFS. Age, regional nodal metastasis, and higher MTV independently predicted shorter OS in multivariate analysis., Conclusion: We found that metabolic parameters derived from FDG-PET/CT could serve as surrogates for disease recurrence in patients with cervical cancer who were treated with definitive chemoradiotherapy. Patients at high risk of distant metastasis could be defined using SUV mean and MTV, and for local recurrence, by using SUV max ., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26-87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients' performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78-7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79-6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12-2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2023 Guler et al.)

Objective: Albumin-globulin ratio or albumin-globulin score predict survival in many cancers, but there are few data on cervical cancer patients. This study examined whether pre-treatment albumin and globulin levels, as well as the albumin-globulin ratio and albumin-globulin score, can predict treatment outcomes in cervical cancer patients undergoing definitive chemoradiotherapy., Methods: A retrospective analysis of cervical cancer patients treated between January 2006 and July 2014 was performed. Receiver operating characteristic curves for serum albumin and globulin levels, as well as albumin-globulin ratio values, were generated in order to determine the cut-off values for these parameters and to predict their sensitivity and specificity for predicting recurrence and survival. Univariate and multivariate analyses were used to identify prognostic factors for overall survival and progression-free survival., Results: A total of 139 patients were included. The median follow-up time was 11.5 years. The 5- and 10-year overall survival rates were 54.7% and 39.3%, while the 5- and 10-year progression-free survival rates were 48.9% and 36.4%, respectively. The optimal cut-off points were 3.79 g/dL for albumin, 3.27 g/dL for globulin, and 1.56 for albumin-globulin ratio. In the univariate analysis, significant prognostic factors for overall survival and progression-free survival were albumin-globulin ratio, albumin-globulin score, patient age, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, lymph node metastasis, and treatment response. Older age, advanced stage, low albumin-globulin ratio, albumin-globulin score of 2, and inadequate treatment response had poor overall survival and progression-free survival in multivariable analysis. However, serum albumin and globulin levels were not found to be a significantly predictive factor for survival. There was a significant correlation between albumin levels, globulin levels, tumor size, stage, lymph node metastasis, and treatment response., Conclusions: Pre-treatment albumin-globulin ratio and albumin-globulin score are useful prognostic factors in patients with cervical squamous cell cancer treated with definitive chemoradiotherapy, and may be suitable biomarkers for predicting treatment outcomes., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact Statement What is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established. What do the results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR. What are the implications of these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.

Objective: We investigated the importance of metabolic parameters measured with 18 F-fluorodeoxyglucose positron-emission tomography integrated with computed tomography (FDG-PET/CT) for predicting progression-free survival (PFS) and overall survival (OS) in cervical cancer with complete metabolic response (CMR) after chemoradiotherapy (ChRT)., Methods: The clinical data and PET parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 122 patients having CMR in post-treatment 18 F-FDG-PET/CT delivered a median of 3.9 months after ChRT completion were analyzed., Results: With a median follow-up of 8.4 years, 55 patients (45%) presented with disease a median of 19.7 months after ChRT. For SUVp, MTVp, TLGp, SUVln, MTVln, and TLGp, the cut-off values for OS determined by receiver operating curve analysis were 15.8, 48.7 cm³, 552.3, 8.7, 7.0 cm³, respectively. All metabolic PET parameters were significant prognostic factors for OS and PFS in univariate analysis. International Federation of Gynecology and Obstetrics (FIGO) stage was predictive of both OS and PFS, while pelvic and/or para-aortic lymph node metastasis were predictive of OS only. In multivariate analysis, FIGO stage ≥IIB, MTVp ≥49.8 cm³, and TLGp ≥597.4 were predictive of worse OS. Advanced stage, presence of lymph node metastasis, higher TLGp, and larger MTVln were significant factors for poor PFS rates., Conclusion: We found that advanced stage and higher TLGp values were significant predictors for poor survival and higher progression rates. Volumetric PET parameters could be used to predict treatment outcomes in patients with CMR after definitive ChRT., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer., Methods: Patients treated with post-operative external beam radiotherapy ± chemotherapy ± vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy., Results: A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors., Conclusion: Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Data supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer., Methods: The clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival., Results: A total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9-95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0-16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities., Conclusions: Patients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. IMPACT STATEMENT What is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group. What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.

We analysed the correlation of 18 F-fluorodeoxyglucose uptake into primary tumours using the maximum standardised uptake value (SUV max ) and the mean apparent diffusion coefficient (ADC mean ) values in magnetic resonance imaging (MRI) with the clinical and pathological factors in patients with cervical cancer who were treated with concurrent chemoradiotherapy. The patients were stratified according to the primary tumour pre-treatment ADC mean and SUV max cut-off values. There were significant correlations between the SUV max of the primary tumour and tumour size, and the treatment response. The correlation between the ADC mean and FIGO stage, tumour size, and the lymph node metastasis was significant. The SUV max was significantly and inversely correlated with the ADC mean for cervical cancer (r = -0.44, p <.001). In the multivariate analysis, the primary tumour ADC mean , treatment response and the lymph node metastasis emerged as significant independent predictors of both OS and DFS, and of the primary tumour SUV max for DFS. Tumour size has a borderline significance for OS. High SUV max and low ADC mean of the primary tumour are important predictive factors for identifying high-risk patients with cervical cancer who are treated with definitive chemoradiotherapy. These results point to a future role for the diffusion-weighted MRI and for 18 F-fluorodeoxyglucose positron emission tomography, not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy for individual patients. Impact statement What is already known on this subject? A negative correlation between primary tumour SUV max derived from positron emission tomography (PET/CT) and ADC min derived from diffusion weighted magnetic resonance imaging (DW-MRI) in various cancer types and cervical cancer has been demonstrated. However, the prognostic value of primary tumour SUV max and ADC mean in cervical cancer patients treated with definitive chemoradiotherapy is not well studied yet. What the results of this study add? The patients with high-risk features (larger tumours, extensive stage, lymph node metastasis) had higher primary tumour SUV max and lower ADC mean values. Primary tumour ADC mean and lymph node metastasis emerged as significant independent predictors of both overall and disease-free survival. This study demonstrated that the functional biomarkers delivered from PET-CT and DW-MRI are important in predicting the treatment outcomes in the squamous cell carcinoma of cervix treated with definitive chemoradiotherapy, where clinical and radiological findings are very important, since these patients are not staged surgically. What are the implications of these findings for clinical practice and/or further research? Based on these findings, there may be a future role of DW-MRI and FDG/PET-CT not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy (ChRT) for individual patients.

Objective: The aim of this study was to investigate the prognostic significance of pretreatment and posttreatment lymphopenia in locally advanced squamous cell carcinoma (SCC) cervical cancer patients treated with definitive chemoradiotherapy (ChRT)., Methods: Data from 95 patients with SCC were retrospectively analyzed. Relationships between pretreatment or posttreatment lymphopenia and patient or tumor characteristics, and overall survival (OS) and disease-free survival (DFS) were evaluated., Results: Median follow-ups for the entire cohort and survivors were 68 months (range, 3-133 months) and 88 months (range, 22-133 months), respectively. Ten patients (11%) exhibited pretreatment lymphopenia, whereas 58 patients (61%) exhibited posttreatment lymphopenia. Median pretreatment total lymphocyte counts decreased from 2029 cells/μL to 506 cells/μL 2 months after ChRT (P < 0.001). The 5-year OS and DFS rates were significantly higher in patients without pretreatment lymphopenia compared with patients with pre-retreatment lymphopenia (61% vs 20% [P < 0.001], 55% vs 20% [P < 0.001]). Patients without posttreatment lymphopenia had significantly higher 5-year OS and DFS rates than their counterparts (70% vs 46% [P = 0.02], 70% vs 39% [P = 0.004]). Complete response (CR) was observed in significantly fewer patients with pretreatment lymphopenia than in those without, after ChRT. Patients with posttreatment lymphopenia had higher rates of lymph node metastasis (P = 0.001) and lower posttreatment CR rates (P = 0.01) versus patients without posttreatment lymphopenia. In univariate analysis, International Federation of Gynecology and Obstetrics stage, tumor size, lymph node metastasis, and treatment response were prognostic for OS and DFS. In multivariate analysis, pretreatment lymphopenia, lymph node metastasis, and treatment response were independent predictors of OS and DFS. Age was predictive of OS. Tumor size was prognostic for DFS., Conclusions: Pretreatment lymphopenia and posttreatment lymphopenia are associated with worse treatment response in patients given ChRT for cervical SCC. Pretreatment lymphopenia is predictive for OS and DFS. Therapeutic strategies including pretreatment or posttreatment immune preservation or modulation may improve response rates and survival in women with cervical SCC.

Objective: To evaluate the prognostic significance of metabolic parameters derived from fludeoxyglucose (FDG) positron emission tomography (PET)/CT, in cervical cancer patients treated with concurrent chemoradiotherapy., Methods: We retrospectively reviewed medical records from 129 biopsy-proven non-metastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at our department. Correlation between metabolic parameters and tumour characteristics was evaluated. Prognostic factors for survival, local control and distant metastasis were analysed., Results: The median follow up for all patients and surviving patients was 30.0 months (range, 3.7-94.7 months) and 50.5 months (range, 14.5-94.7 months), respectively. The 2- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 68 42, 54 and 38%, respectively. The maximum standardized uptake value (SUV max ), SUV mean , metabolic tumour volume (MTV) and total lesion glycolysis were significantly higher in patients with larger tumours (>4 cm) and partial regression or progressive disease after definitive treatment compared to patients with smaller tumour (≤4 cm) and post-treatment complete response. On univariate analysis, stage, lymph node metastasis, tumour size >4 cm, SUV max , MTV, SUV mean and total lesion glycolysis were prognostic factors for OS and DFS. On multivariate analysis, only larger tumour and presence of lymph node metastasis were significant prognostic factors for both OS and DFS. Additionally, extensive stage was a significant prognosticator for DFS., Conclusion: Although, metabolic parameters derived from FDG-PET/CT had a prognostic significance in univariate analysis, the significance was lost in multivariate analysis where tumour stage, size and lymph node status were the only independent parameters. Advances in knowledge: The clinical benefit of using FDG-PET/CT metabolic parameters to evaluate the high-risk patients among cervical cancer patients and to eventually change patient management still needs further clarification.

Objective: The aim of the study was to investigate the prognostic factors for survival and treatment-related toxicities in older (≥65 years) cervical cancer patients treated with definitive chemoradiotherapy. In addition, we sought to compare the outcomes between the older elderly (≥75 years) and their younger old counterparts (age, 65-74 years)., Materials and Methods: We retrospectively reviewed medical records from 269 biopsy-proven nonmetastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at the departments of radiation oncology in 2 different universities. The prognostic factors for survival, local control, and distant metastasis (DM) were analyzed., Results: The median follow-up time was 38.8 months (range, 1.5-175.5 months) for the entire cohort and 70.0 months (range, 6.1-175.7 months) for survivors. The 2- and 5-year overall survival (OS), disease-free survival (DFS), and cause-specific survival rates were 66% and 42%, 63% and 39%, and 72% and 55%, respectively. Patients 75 years or older showed significantly worse OS compared with patients aged 65 to 74 years but showed no significant difference in DFS. The 2- and 5-year local control rates were 86% and 71%, respectively. The incidences of DMs at 2 and 5 years were 22% and 30%, respectively. In multivariate analysis, vaginal infiltration and lymph node metastasis were predictive of OS, DFS, local recurrence, and DM. Concomitant chemotherapy was predictive of OS, DFS, and local recurrence, and larger tumor (>4 cm) was a significant prognostic factor for local recurrence. None of the patients had toxicity that necessitated the discontinuation of radiotherapy. All patients were evaluable for acute toxicity, and no grade higher than 3 adverse events occurred during external beam radiation therapy or brachytherapy., Conclusions: Although age limited the delivery of aggressive treatment, concurrent chemoradiotherapy in elderly patients associated with improved outcomes similar as in younger counterparts without increasing serious acute and late toxicities.

Background Further research is required for evaluating the use of ADC histogram analysis in more advanced stages of cervical cancer treated with definitive chemoradiotherapy (CRT). Purpose To investigate the utility of apparent diffusion coefficient (ADC) histogram derived from diffusion-weighted magnetic resonance images in cervical cancer patients treated with definitive CRT. Material and Methods The clinical and radiological data of 50 patients with histologically proven cervical squamous cell carcinoma treated with definitive CRT were retrospectively analyzed. The impact of clinicopathological factors and ADC histogram parameters on prognostic factors and treatment outcomes was assessed. Results The mean and median ADC values for the cohort were 1.043 ± 0.135 × 10 -3 mm 2 /s and 1.018 × 10 -3 mm 2 /s (range, 0.787-1.443 × 10 -3 mm 2 /s). The mean ADC was significantly lower for patients with advanced stage (≥IIB) or lymph node metastasis compared with patients with stage

Purpose: To investigate the pre- and posttreatment mean apparent diffusion coefficient (ADCmean ) of cervical cancer tumors treated with definitive chemoradiotherapy (CRT) and evaluate their correlation with recurrence and survival rates., Materials and Methods: Forty-four patients with cervical squamous cell carcinoma were retrospectively evaluated. All patients underwent multiparametric 1.5T magnetic resonance imaging (MRI) including T2 -weighted, fat-saturated T2 -weighted, dynamic contrast-enhanced (DCE), and diffusion-weighted imaging (DWI) sequences before and after treatment. Posttreatment MR images were acquired within a median of 3.2 months (range, 2.8-4.1 months) after completing CRT. We assessed the impact of primary tumor pre- and posttreatment ADC values on prognostic factors and treatment outcomes., Results: The pre- and posttreatment ADCmean values were 0.882 ± 0.096 × 10(-3) mm(2) /sec and 1.159 ± 0.168 × 10(-3) mm(2) /sec, respectively, and the difference was statistically significant (P < 0.001). The median percent ADC change was 33.7% (range, 5.0-70.0%). Patients with disease recurrence had lower ADC values, both pretreatment (0.822 ± 0.096 × 10(-3) mm(2) /sec vs. 0.936 ± 0.058 × 10(-3) mm(2) /sec; P < 0.001) and posttreatment (1.060 ± 0.116 × 10(-3) mm(2) /sec vs. 1.248 ± 0.160 × 10(-3) mm(2) /sec; P < 0.001). The ADC change was lower in patients with recurrence (25.7% ± 13.0% vs. 42.8% ± 15.7; P < 0.001) than in patients without recurrence. In multivariate analysis, pelvic lymph node metastasis and pretreatment ADCmean were prognostic factors for overall survival (OS) and disease-free survival (DFS). ADC change between pre- and posttreatment DW-MRI was a prognostic factor for OS., Conclusion: DWI parameters, measured before and after treatment, may be useful prognostic biomarkers for tumor burden, recurrence, and survival in cervical cancer patients treated with CRT. The primary tumor pretreatment ADCmean is an independent prognostic factor for DFS and OS. J. MAGN. RESON. IMAGING 2016;44:1010-1019., (© 2016 International Society for Magnetic Resonance in Medicine.)

Objectives: The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer., Methods: In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed., Results: Median pretreatment NLR and PLR were 3.03 (range, 1.04-13.03) and 133.02 (range, 36.3-518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905-5.790; PFS: HR, 3.579; 95% CI, 2.106-6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706-4.023; PFS: HR, 2.989; 95% CI, 1.918-4.378; both P < 0.001), although patients' age (HR, 1.019; 95% CI, 1.003-1.035; P = 0.02) was also significantly predictive of OS., Conclusions: Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients' age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.

Purpose: To evaluate the prognostic significance of the maximum standardized uptake (SUVmax) value for pelvic lymph nodes in patients with cervical cancer and its impact on treatment response, disease control, and survival., Methods: Ninety-three patients with pelvic or para-aortic metastasis detected by PET/CT and treated with definitive chemoradiotherapy were evaluated. The impact of pelvic lymph node SUVmax on prognostic factors and treatment outcomes was assessed., Results: The size and SUVmax of pelvic lymph nodes were significantly correlated (r=0.859; p<0.001). Patients with pelvic and para-aortic lymph node metastases had significantly higher SUVmax values for both primary tumor (23.4±9.2 vs. 18.5±7.3; p=0.01) and pelvic lymph nodes (11.4±4.6 vs. 7.4±3.8; p=0.001). Patients with pelvic lymph node SUVmax≥7.5 had significantly higher primary tumor SUVmax, larger pelvic lymph nodes, higher rates of para-aortic lymph node metastasis, and lower post-therapy complete response rates. Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with SUVmax<7.5 compared to patients with SUVmax≥7.5. In a multivariate analysis, pelvic lymph node SUVmax and post-therapy metabolic response were significant prognostic factors for both OS and DFS for all patients, but no significant prognostic factors were found in pelvic lymph node metastasis only., Conclusions: Patients with highly FDG-avid pelvic lymph nodes have a higher risk of disease recurrence with worse survival. Identification of these patients may assist in the evaluation of the clinical benefits of additional treatments., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We sought to evaluate failure patterns and prognostic factors predictive of recurrences and survival in cervical cancer patients who are treated with definitive chemoradiotherapy (ChRT), who have a subsequent complete metabolic response (CMR) with (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET) after treatment., Methods: The records of 152 cervical cancer patients who were treated with definitive chemoradiotherapy were evaluated. All patients underwent pre-treatment positron emission tomography (PET-CT), and post-treatment PET-CT was performed within a median of 3.9 months (range, 3.0-9.8 months) after the completion of ChRT. The prognoses of partial response/progressive disease (PR/PD) cases (30 patients, 18 %) and CMR cases (122 patients, %82) were evaluated. Univariate and multivariate analysis effecting the treatment outcome was performed in CMR cases., Results: The median follow-ups for all patients and surviving patients were 28.7 (range, 3.3-78.7 months) and 33.2 months (range, 6.23-78.7 months), respectively. Four-year overall survival (OS) rate was significantly better in patients with CMR compared to patients with PR/PD (66.9 % vs. 12.4 %, p < 0.001, respectively). Patients with PR/PD had higher maximum standardized uptake value (SUVmax) of primary cervical tumor (26.4 ± 10.1 vs. 15.9 ± 6.3; p < 0.001) and larger tumor (6.4 cm ± 2.3 cm vs. 5.0 cm ± 1.4 cm; p < 0.001) compared to patients with CMR. Of the 122 patients with post-treatment CMRs, 25 (21 %) developed local, locoregional, or distant failure. In univariate analysis, tumor size ≥ 5 cm, 'International Federation of Obstetricians and Gynecologists' (FIGO) stage ≥ IIB, and pelvic and/or para-aortic lymph node metastasis were predictive of both overall survival (OS) and disease-free survival (DFS), while histology was predictive of only OS. In multivariate analysis, tumor size, stage and lymph node metastasis were predictive of OS and DFS., Conclusion: Although CMR is associated with better outcomes, relapses remain problematic, especially in patients with bulky tumors (≥ 5 cm), extensive stage (≥ IIB) or pelvic and/or para-aortic lymph node metastasis. These findings could support the need for more aggressive treatment or adjuvant chemotherapy regimens.

Objectives: This study aimed to determine the incidence and characteristics of uterine perforation at our department using 3-dimensional computed tomography (CT)-based brachytherapy (BRT). The characteristics of the patients presenting with perforation and impact of the perforation on the treatment course were also analyzed., Materials and Methods: The clinical and radiologic data of 200 patients with biopsy-proven cervical cancer treated using CT-based BRT were retrospectively evaluated. All patients had undergone tandem-based intracavitary BRT, and 67 patients had undergone magnetic resonance imaging (MRI) before BRT., Results: Of the 200 patients, 17 (8.5%) had uterine perforation. Of the 626 applications with CT images, 30 (4.8%) resulted in uterine perforation. The median age of patients with perforation was higher (68 years; range, 44-89 years) than that of the patients without perforation (59 years; range, 21-87 years), and the mean (SD) tumor size at diagnosis was larger in patients with perforation (7.0 [1.5] cm) than in patients without perforation (5.0 [1.5] cm). The most frequent perforation site was the posterior uterine wall (8 patients), followed by the fundus (5 patients) and anterior wall (4 patients). Of the 7 patients with a retroverted uterus, 4 had uterine perforation during BRT. In 67 patients with MRI delivered before BRT, only 3 (4%) had uterine perforation, and 2 of the 3 patients with uterine perforation had a retroverted uterus. However, of the 133 patients with no MRI evaluation before BRT, 14 (11%) had uterine perforation. No life-threatening complications or signs of intraperitoneal tumor cell seeding were observed., Conclusions: Older age, larger tumors, a retroverted uterus, and a stenotic cervical os were all predisposing factors for uterine perforation during BRT. Preoperative MRI is a feasible and safe method to decrease the risks of uterine perforation and could be used preoperatively in centers where intraoperative ultrasonography is not used in routine practice.

Objective: We analyzed the correlation of F-fluorodeoxyglucose (FDG) uptake into primary tumors using the maximum standardized uptake value (SUVmax) and clinicopathological factors of disease. The impact of the pretreatment SUVmax of the primary tumor on survival was investigated., Materials and Methods: The records of 149 patients with biopsy-proven cervical cancer treated with definitive chemoradiotherapy (ChRT) were reviewed. All patients underwent pretreatment FDG positron emission tomography with computed tomography, and posttherapy FDG positron emission tomography with computed tomography was performed within a median interval of 4.2 months (range, 3.0-11.2 months) after the completion of chemoradiotherapy., Results: The mean SUVmax in patients with lymph node metastasis was significantly higher than that in patients without metastasis (19.7 ± 8.2 vs 16.4 ± 8.2, respectively; P = 0.01). A significant difference existed between tumor size (<4 vs ≥4 cm) and the primary tumor SUVmax (14.7 ± 6.6 vs 18.7 ± 8.5, respectively; P = 0.02). The primary tumor pretreatment SUVmax for patients with complete remission was significantly lower than that of patients with partial response or progressive disease (15.6 ± 5.7 vs 28.0 ± 9.9, respectively; P < 0.001). The relationship between primary tumor FDG uptake and survival was evaluated by the cutoff value determined by receiver operating characteristic curve analysis. The area under the curve was 0.901 (P < 0.001; 95% confidence interval, 0.848-0.954), and 15.6 was determined as the SUVmax cutoff value. The 4-year actuarial overall survival (OS) and disease-free survival for SUVmax of less than 15.6 compared with SUVmax of 15.6 or greater were 85% vs 34% (P < 0.001) and 80% vs 29%, respectively (P < 0.001). In multivariate analysis, age, SUVmax of 15.6 or greater, and lymph node metastasis were independent prognostic factors of OS, and International Federation of Gynecology and Obstetrics stage IIB or higher, SUVmax of 15.6 or greater, and lymph node metastasis were significant factors for disease-free survival., Conclusion: The primary tumor pretreatment SUVmax is correlated with increased tumor size and lymph node involvement at diagnosis, how well the primary tumor responds to treatment, the likelihood of disease recurrence, and OS.

Objective: This study aimed to evaluate the degree of mediastinal involvement in patients with cervical cancer with isolated mediastinal [F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) positivity as verified by histopathologic examination., Methods: Two hundred twenty-eight patients with newly diagnosed cervical cancer and who underwent FDG-PET imaging were analyzed. Twenty-nine patients (17%) had disseminated disease detected with PET/computed tomography (CT). Only 10 patients (4%) had increased FDG uptake in mediastinal lymph nodes alone. Of the 10 patients with mediastinal disease, 2 refused surgical mediastinal lymph node biopsy and did not receive any treatment. Patients with suspected paratracheal or subcarinal lymph node metastasis detected on PET/CT underwent mediastinoscopy, and those with hilar metastasis had video-assisted mediastinal lymphadenectomy. Treatment was delivered according to final staging based on histopathologic confirmation of mediastinal lymph node involvement., Results: The mean (SD) maximum standardized uptake values for primary cervical tumor and mediastinal lymph nodes were 19.7 (10.3) and 7.5 (1.6), respectively. Of 8 patients who underwent mediastinal lymph node confirmation, 6 (75%) were tumor free, demonstrating granulomatous changes, and were treated curatively. No patients had residual or recurrent disease at the primary site, and all but 1 were alive without disease. Two patients with confirmed mediastinal lymph node metastasis were treated palliatively and died between 9 and 11 months after diagnosis., Conclusions: Positron emission tomography/CT is an important tool for lymphatic staging and evaluation of distant metastases in cervical cancer. However, PET/CT should be interpreted cautiously for isolated mediastinal involvement; surgical evaluation is required for accurate staging and appropriate treatment decisions to achieve better outcomes.

Background: To compare intracavitary brachytherapy (ICBT) planning methods for cervical cancer, based on either orthogonal radiographs (conventional plan) or CT sections (CT plan); the comparison focused on target volume coverage and dose volume analysis of organs at risk (OARs), by representing point doses defined by the International Commission on Radiation Units and Measurement (ICRU) and dose volume histograms (DVHs) from 3D planning., Methods: We analyzed the dosimetric data for 62 conventional and CT-based ICBT plans. The gross tumor volume (GTV), clinical target volume (CTV) and organs at risk (OAR)s were contoured on the CT-plan. Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images., Results: Patients were categorized on the basis of whether the >95% isodose line of the point-A prescription dose encompassed the CTV (group 1, n = 24) or not (group 2, n = 38). The mean GTV and CTV (8.1 cc and 20.6 cc) were smaller in group 1 than in group 2 (24.7 cc and 48.4 cc) (P <0.001). The mean percentage of GTV and CTV coverage with the 7 Gy isodose was 93.1% and 88.2% for all patients, and decreased with increasing tumor size and stage. The mean D2 and D5 rectum doses were 1.66 and 1.42 times higher than the corresponding ICRU point doses and the mean D2 and D5 bladder doses were 1.51 and 1.28 times higher. The differences between the ICRU dose and the D2 and D5 doses were significantly higher in group 2 than in group 1 for the bladder, but not for the rectum., Conclusion: The CT-plan is superior to the conventional plan in target volume coverage and appropriate evaluation of OARs, as the conventional plan overestimates tumor doses and underestimates OAR doses.