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Supplemental digital content is available in the text. Objective: To evaluate the effects of body mass index (BMI) and weight change during radiotherapy on the development of toxicity in patients with locally advanced cervical cancer (LACC) treated with intensity-modulated radiotherapy (IMRT). Methods: A total of 245 patients were analyzed after undergoing definitive IMRT treatment between 2004 and 2015 for stage IB2 to stage IVA LACC. The patients were divided into 3 groups: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5–24.9 kg/m2), and overweight (BMI ≥25.0 kg/m2). The relationships between toxicity, clinical factors, and the bowel dose-volume histogram were analyzed. V45 indicated the bowel volume that received a radiation dose of 45 Gy. Results: The median follow-up period was 63 months. The V45 was similar among the 3 groups. The 5-year rates of grade 3 or higher late gastrointestinal toxicities were 18.6%, 4.0%, and 4.2% for the underweight, normal weight, and overweight groups, respectively (P = 0.002). In the multivariable analysis, underweight (hazard ratio, 13.99; 95% confidence interval, 3.22-60.82; P < 0.001) and weight loss (> −5%) (hazard ratio, 5.91; 95% confidence interval, 1.75-19.98; P = 0.004) were significant predictors of grade 3 or higher-grade late gastrointestinal toxicities. Conclusion: A BMI of less than 18.5 kg/m2 and weight loss (> −5%) were associated with a higher risk of grade ≥3 or higher late gastrointestinal toxicity in patients with LACC treated with definitive IMRT. Future research on the development of a standardized and structured approach to improve the therapeutic ratio for the supportive care of patients with LACC is needed. [ABSTRACT FROM AUTHOR]

Concurrent chemoradiotherapy is a standard treatment of locally advanced cervical carcinoma. The most widely used drug for chemoirradiation is cisplatin. However, its toxicity and drug resistance remain major concerns in clinical practice. This study was designed to evaluate the effect of oxaliplatin, another platinum compound, on enhancing radiosensitivity in cervical cancer cell lines. Human HeLa and SiHa cells were used. Cell survival after irradiation with or without oxaliplatin pretreatment was assessed by performing colony-formation assays. Sensitizer enhancement ratios were calculated using a linear quadratic model. Cell morphology was observed after staining with Wright dye. To evaluate the machinery to repair DNA damage, cellular protein was subjected to Western blotting to assess the expression of damage-related molecules. Nontoxic doses of oxaliplatin were 5 and 10 μmol/L for HeLa and SiHa cells, respectively. Pretreatment with oxaliplatin markedly decreased, with a greater extent than cisplatin, the survival of irradiated HeLa cells. Maximal sensitizer enhancement ratios of oxaliplatin at 37% survival were 3.4 for HeLa cells and 4.8 for SiHa cells. Oxaliplatin pretreatment enhanced the cell cycle arrest in the G2/M phase and the radiation-induced mitotic catastrophe. Oxaliplatin modulated radiation-induced DNA double-strand breaks, as indicated by delayed abrogation of γ-H2AX, attenuation of radiation-induced phosphorylation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2. In conclusion, oxaliplatin sensitized human HeLa and SiHa cells to ionizing radiation. This effect may involve modulation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2 activation during DNA damage repair.Abbreviations: SERs - Sensitizer enhancement ratios, ATM - ataxia telangiectasia-mutated, Chk2 - checkpoint kinase 2, MTT - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide [ABSTRACT FROM AUTHOR]

Purpose . To evaluate the relation between tumor response, treatment toxicity, and serum cytokine profiles in patients with cervical cancer receiving cisplatin-based chemoradiation. Patients and Methods . Forty-two patients with cervical carcinoma receiving chemoradiation were recruited. Hemogram, biochemistry profile, cytokine levels, tumor size, and toxicity were assessed weekly. Results . The absolute neutrophil count decreased accompanied by an increase in serum levels of G-CSF during chemoradiation. The sudden elevation of serum TGF-β 1 and VEGF levels after the first fraction of brachytherapy accompanied with the development of greater radiation therapy (RT) morbidity. Lower pretreatment TGF-β 1 and VEGF levels are associated with tumor response to chemoradiation. Conclusion . The serial changes in serum cytokines during chemoradiation may correlate with tumor regression and treatment morbidity. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate whether computed tomography (CT)-based muscle measurement predicts distant failure in patients with locally advanced cervical cancer (LACC). Data from 278 patients with LACC who underwent chemoradiation therapy (CCRT) between 2004 and 2017 were analysed. Changes in the skeletal muscle index (SMI), skeletal muscle density, and total adipose tissue index during CCRT were calculated from CT images taken at the baseline and after CCRT. The predictive capability of CT-based muscle measurement for distant failure was evaluated using Cox proportional hazards regression, Harrell's concordance index (C-index), and time-dependent receiver operating characteristic curves. SMI loss ≥ 5% was independently associated with worse distant recurrence-free survival (DRFS) (HR: 6.31, 95% CI: 3.18–12.53; p < 0.001). The addition of muscle change to clinical models, including International Federation of Gynaecology and Obstetrics (FIGO) stage, lymph nodes, pathology, and squamous cell carcinoma-antigen, achieved higher C-indices (0.824 vs. 0.756; p < 0.001). Models including muscle change had superior C-indices than those including weight change (0.824 vs. 0.758; p < 0.001). The area under the curve for predicting 3-year DRFS was the highest for the muscle-loss model (0.802, muscle-loss model; 0.635, clinical model; and 0.646, weight-loss model). Our study demonstrated that muscle loss after CCRT was independently associated with worse DRFS and that integrating muscle loss into models including classical prognostic factors improved the prediction of distant failure. [ABSTRACT FROM AUTHOR]

Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. This study evaluated the feasibility of neoadjuvant CCRT as a larynx preservation strategy for treating cervical esophageal squamous cell carcinoma (SCC) by a multidisciplinary team. Fifteen patients with cervical esophageal SCC who received neoadjuvant CCRT and radical surgery at our institution were reviewed. All patients received CCRT using the intensity-modulated radiation therapy with 48 Gy to gross tumor and 43.2 Gy to regional lymphatic basin in 24 fractions. Side effects, clinical tumor responses, pathological responses, and surgical margin status were analyzed. Pathological T down-staging was noted in seven patients (46.7%); pathological complete response was achieved in three patients (20%). Fourteen patients (93.3%) had larynx preservation; eight patients (53.3%) achieved negative surgical margins. The 2-year overall survival, local relapse-free survival, and regional relapse-free survival were 50.6%, 62.2%, and 47.5%, respectively. Neoadjuvant CCRT and larynx-sparing surgery are feasible and tolerable in patients with cervical esophageal SCC. Prospectively designed studies for large patient groups and long-term follow-up results are needed for validating this multimodality therapy. [ABSTRACT FROM AUTHOR]

Objectives A previous study has suggested the benefit of sub-renal vein radiotherapy (SRVRT) for pelvic lymph node (PLN)-positive cervical cancer. In order to better select patients for SRVRT, this study aimed to evaluate the value of a risk-based radiation field based on PLN location and number in PLN-positive cervical cancer. Methods We reviewed 198 patients with FIGO stage IB2–IVA cervical cancer, positive PLNs, and negative para-aortic lymph nodes (PALNs) from 2004 to 2015 at two tertiary centers. All patients underwent pelvic radiotherapy (PRT) or SRVRT with IMRT. The SRVRT extended the PRT field cranially to the level of the left renal vein. The prescribed doses were 45–50.4 Gy in 1.8 Gy per fraction. Results Overall, 118 and 80 patients underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease based on FIGO stage, common iliac PLNs, and number of PLNs. The median follow-up was 63 months (range: 7–151 months). PALN failure was experienced by 28 patients (23.7%) in the PRT group and 1 patient (1.3%) in the SRVRT group ( p < 0.001). Compared with PRT, SRVRT significantly improved 5-year PALN recurrence-free survival (56.8% vs. 100%, p < 0.001) and cancer-specific survival (56.5% vs. 93.9%, p < 0.001) among patients with common iliac PLNs or ≥ 3 PLNs. No significant differences were observed in these outcomes among patients with PLNs below the common iliac bifurcation and 1–2 PLNs. The SRVRT did not increase severe toxicities. Conclusions Risk-based radiation field based on PLN location and number could optimize outcomes for PLN-positive cervical cancer. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of prophylactic sub-renal vein radiotherapy (SRVRT) using intensity-modulated radiotherapy (IMRT) for cervical cancer. Methods A total of 206 patients with FIGO stage IB2–IVA cervical cancer and negative para-aortic lymph nodes (PALNs) who underwent pelvic IMRT (PRT) or SRVRT between 2004 and 2013 at our institution were reviewed. SRVRT cranially extended the PRT field for PALNs up to the left renal vein level. The prescribed dose was consistent 50.4 Gy in 28 fractions. Results Overall, 110 and 96 patients underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease based on FIGO stage and positive pelvic lymph nodes (PLNs). The median follow-up time was 60 months (range, 7–143). For the total study population, the 5-year PALN recurrence-free survival (PARFS) and overall survival (OS) for PRT vs. SRVRT were 87.6% vs. 97.9% ( p = 0.03) and 74.5% vs. 87.8% ( p = 0.04), respectively. In patients with FIGO III–IVA or positive PLNs, the 5-year PARFS and OS for PRT vs. SRVRT were 80.1% vs. 96.4% ( p = 0.02) and 58.1% vs. 83.5% ( p = 0.012), respectively. However, there were no significant differences in these outcomes for patients with FIGO IB–IIB and negative PLNs. In a multivariate analysis, only SRVRT was associated with better PARFS (HR, 0.21; 95% CI, 0.06–0.78; p = 0.02). The SRVRT did not significantly increase severe late toxicities. Conclusion Prophylactic SRVRT using IMRT reduced PALN recurrence with tolerable toxicities, supporting the application of risk-based radiation fields for cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: Point A, used for dose specification for intracavitary brachytherapy for cervical cancer, is the point at which the uterine artery and ureter cross. This study assessed compatibility of commonly used traditional point A (TPA) and actual anatomic point A (APA). Methods and Materials: We visualized and placed radiopaque clips at the APA during pelvic and paraaortic lymphadenectomy in 11 patients with cervical carcinoma. Orthogonal and oblique radiographs were obtained after insertion of brachytherapy applicators. We measured the distance between the TPA and APA and estimated the brachytherapy dose to each of the two points. Results: A total of 64 brachytherapy treatments were performed. The mean distances between the TPA and APA were 5.2 +/- 1.0 cm on the right and 5.4 +/- 1.1 cm on the left. The estimated brachytherapy doses delivered to the APA as a percentage of the presumed 500-cGy fraction size to the TPA were 35.2% (176.6 +/- 59.0 cGy) on the right and 30.0% (150.2 +/- 42.9 cGy) on the left. The marked discrepancy in the position of the two points was not related to individual kinetic variations during brachytherapy treatment, tumor size, or bladder filling. Conclusions: The conventional TPA does not provide an accurate estimate of the APA determined during lymphadenectomy, indicating a need to reevaluate the current practice for determining the brachytherapy prescription for cervical cancer. (ClinicalTrials.gov Identifier, NCT00319462). [ABSTRACT FROM AUTHOR]