Stage IIB-IVA Cervical Cancer Research Articles

To study the survival outcomes of uncommon recurrences among patients with cervical cancer compared with loco-regional and nodal recurrences at a tertiary care center in North East India – Bridging the knowledge gap in the existing literature.

BackgroundRecurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer 28–64 respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual sites and theirrecurrence pattern for unusual sites and its association with survival and prognosis. ObjectiveTo study overall survival in patients with distant metastasis compared to local and regional nodal metastasis. MethodsA retrospective study was done from 1/1/2017 to 30/12/22. Cervical cancer patients post primary treatments were included. Survival was analyzed with respect to 3 groups local, regional nodalconducted from 1/1/2017 to 30/12/22. Cervical cancer patients who had received primary post-primary treatments were included. Survival was analyzed with respect to three groups: local, regional nodal, and distant metastasis. Results225 patients had recurrences post-completion of primary treatment, of which 105 (46.6%)(46.6 %) had local, 46 (20.4%)(20.4 %) had regional nodal, and 74 (33.3%) had distant recurrences. The median time for recurrence in local, regional nodal, and atypical recurrences were 9, 9, and 13 months (p value - <0.05), respectively. Treatment included systemic chemotherapy 122 (54.2%), metronomic therapy 19 (8.4%), palliative radiotherapy 44 (19.5%), palliative surgery 8 (3.5%) and best supportive care 30 (13.3%) patients. Median Time to treatment-death of patients after recurrence in local, nodal and distant recurrences was 17.0 months, 18.0 months and 10.0 months respectively (p value - < 0.05). Overall Survival of patients after primary treatment with local, nodal and distant recurrences was 35.0 months, 47.0 months and 50.0 months respectively (p value <0.05). ConclusionLocal recurrence is most common, followed by regional, nodal, and distant recurrences. Overall survival post recurrence was lowest for distant recurrences and highest for local recurrences however overall survival after primary treatment completion was highest for distant recurrence due to the late presen; however, tation of distant recurrences.

Clinical research of the value of high-risk CTV setting on intensity-modulated radiotherapy for stage IIB-IVA cervical cancer

BackgroundThis study aims to evaluate the clinical efficacy and side effects of setting up a high-risk clinical target volume (CTV-hr) alongside simultaneous integrated boost intensity-modulated radiotherapy (IMRT-SIB) in patients diagnosed with stage IIB-IVA cervical cancer.MethodsThis study retrospectively analysed patients with stage IIB-IVA cervical cancer who received radical radiotherapy at the Affiliated Hospital of Qingdao University between November 2014 and September 2019. The patients were divided into experimental and control groups based on whether CTV-hr was set. All patients received a combined treatment of radiotherapy and chemotherapy. The dosage for paclitaxel was 135 mg/m2, while for cisplatin it was 75 mg/m2 or for carboplatin it was AUC 4–6, given in a cycle of 21 days. Radiotherapy (RT) included external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). In the control group, positive lymph nodes (GTV-n) were treated at a dose of 58–62 Gy/26–28 fractions(f), while clinical target volumes (CTV) were treated with a dose of 46–48 Gy/26-28f. The experimental group received a simultaneous integrated boost (SIB) to CTV-hr at a dose of 54–56 Gy/26-28f, with the same CTV and GTV-n as the control group. Both groups were combined with brachytherapy with a total dose (EQD2, the equivalent dose in 2 Gy/f) of 80-90 Gy. The study measured objective remission rate (ORR), 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, recurrence rate, and side effects as endpoints.ResultsThe study enrolled 217 patients, with 119 in the experimental group and 98 in the control group. Results showed that the experimental group had a higher 3-year OS rate (87.4% vs. 71.4%, p = 0.001) and 3-year PFS rate (72.3% vs. 51.0%, p = 0.000) compared to the control group. Additionally, the experimental group had significantly lower rates of overall recurrence (26.1% vs. 50.0%, p = 0.003), in-field recurrence (15.1% vs. 36.7%, p = 0.000), and out-field recurrence(13.4% vs. 35.7%, p = 0.000) compared to the control group. All observed differences were found to be statistically significant. However, the experimental and control groups had no statistically significant difference in ORR and radiological side effects, such as radiation cystitis and enteritis (p > 0.05).ConclusionsSetting CTV-hr and performing IMRT-SIB on patients with stage IIB-IVA cervical cancer effectively increased the 3-year OS rate, 3-year PFS rate and reduced recurrence rate, with no significant differences in side effects.

Anlotinib plus chemoradiotherapy in the treatment for FIGO stage IB3 and IIB-IVA cervical cancer: A prospective single-arm, single-center, exploratory phase II trial (299)

<b>Objectives:</b> Cervical carcinoma is the fourth leading cause of cancer-related death among women worldwide. Previous randomized clinical trials showed a 30% to 50% decrease in risk of death in locally advanced cervical cancer (LACC) with the addition of concurrent platinum-based chemoradiotherapy when compared with radiotherapy alone. Mechanisms to account for improved efficacy are thought to include direct cytotoxicity, radiosensitization of tumor cells, and control of subclinical metastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib synergizes with radiation and cisplatin, as shown in preclinical and clinical studies. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to concurrent chemoradiotherapy in FIGO stage IB3 and IIB-IVA cervical cancer. <b>Methods:</b> Inclusion criteria include treatment-naive histologically confirmed FIGO stage IB3 to IVA cervical cancer with at least one measurable lesion and ECOG performance score 0-2 within the age range of 18 to 75 years. Abundant organ functions are required, with no contraindication to anlotinib or chemoradiation present. Patients will be treated with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total 3 cycles) and X-ray external-beam radiotherapy (total 45Gy-50Gy in 25-28 fraction), followed by brachytherapy (6Gy/5 fractions or 7Gy/4 fractions) with concurrent cisplatin (40 mg/m2 weekly for 5-6 weeks). The primary endpoint is the progression-free survival (PFS) rate at three years. The secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and quality of Life (QOL). Safety will be evaluated in all patients who receive study drugs according to the treatment received (safety population) by recording clinical adverse events (AEs) using National Cancer Institute Common. The sample size calculation of 47 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test; considering a 10% reduction, a total of 53 samples are required. This study is currently open, and 23 patients have been enrolled. The estimated primary completion date is December 1, 2024, and the estimated study completion date is October 31, 2025.

Survival Comparison Between Squamous Cell Carcinoma and Adenocarcinoma for Radiotherapy-Treated Patients with Stage IIB-IVA Cervical Cancer.

ObjectiveTo compare the prognostic significance of adenocarcinoma (AC) with squamous cell carcinoma (SCC) on overall survival (OS) in patients with stage IIB-IVA cervical cancer (CC) treated by external beam radiotherapy (EBRT) and brachytherapy (BRT) with/without chemotherapy registered in the Surveillance, Epidemiology, and End Results database.MethodsData of eligible patients were extracted between 2004 and 2016. A univariate analysis was conducted using the cumulative incidence function (CIF) by considering competing events and compared using Gray’s test. The significant variables in univariate analysis were further evaluated in a multivariate analysis performed with the Fine-Gray regression model. Propensity score matching (PSM) analysis was also employed to reconfirm the results found in the present study.ResultsA total of 2,243 patients with SCC and 176 patients with AC were extracted from the database. The 5-year OS rates were 57.8% in the SCC group and 52.8% in the AC group. 149 patients died of causes other than CC—considered as competing events. Compared with the SCC group, patients diagnosed with AC had statistically significant worse 5-year OS rate before and after PSM. In the multivariate Fine-Gray regression model, the histological subtype of AC was proven as an independent prognostic factor associated with poorer OS before [hazard ratio (HR) = 1.340; 95% confidence interval (CI): 1.081-1.660; P = 0.007] and after [HR = 1.376; 95% CI: 1.107-1.711; P = 0.004] PSM.ConclusionsThe histological subtype of AC is significantly correlated with impaired OS as an independent prognostic variable in patients with stage IIB-IVA CC who received EBRT and BRT compared to patients with SCC. Future studies should incorporate effective and individualized treatment strategies into clinical decision-making to improve the unsatisfactory survival outcomes for patients with AC.

Evaluation of sociodemographic and baseline patient characteristic differences in cervical cancer patients treated with either external beam or brachytherapy boost

Chemoradiation is considered the standard of care for locally advanced cervical cancer. While brachytherapy (BT) boost is associated with improved survival and less toxicity compared to external beam radiation therapy (EBRT) boost, it is unclear why many patients do not receive a BT boost. In this study, we compared sociodemographic and baseline patient characteristics between patients receiving EBRT boost versus BT boost. We analyzed patients in the National Cancer Database diagnosed between 2004 and 2016 with FIGO stage IIB-IVA cervical cancer treated with nonpalliative doses of chemoradiation. Logistic regression analysis was utilized to evaluate BT utilization over time and by other clinicopathological and sociodemographic factors. Overall, 5764 patients were evaluated, of which 4937 (86%) underwent BT boost. Using multivariable logistic regression, higher FIGO stage was a significant predictor for utilization of EBRT versus BT boost, with odds ratio 2.92 (95% confidence interval [CI] 2.04-4.16; p < 0.001), 2.68 (95%CI 2.22-3.24; p < 0.001), and 4.51 (95%CI 3.05-6.67; p < 0.001) for IIIA, IIIB, and IVA, respectively, compared to IIB. Increased utilization of EBRT boost was also associated with community cancer facility types, lower income (based on zip code), earlier year of diagnosis, and higher comorbidity score. In FIGO stage IIB-IVA cervical cancer patients treated with nonpalliative doses of chemoradiation, overall utilization of BT is 86%. Higher FIGO stage, community cancer facilities, lower income, earlier year of diagnosis, and higher comorbidity score were significant predictors of EBRT boost utilization. Future studies are needed to better understand reasons for this as higher FIGO stage patients are the mostly likely to benefit from a BT boost.

Medicaid Expansion Through the Affordable Care Act and Receipt of Guideline Recommended Brachytherapy for Locally Advanced Cervical Cancer

Brachytherapy is a critical component of definitive chemo-radiation for locally advanced cervical cancer. However, studies have shown that a large portion of patients do not received brachytherapy as part of their treatment. We hypothesized that access to care due to lack of insurance might prevent patients from receiving brachytherapy as part of their treatment, and patients in states that expanded Medicaid under the affordable care act would therefore be more likely to receive brachytherapy after expansion.The National Cancer Database was queried for cases from 2004 to 2016 of women with stage IIb-IVa cervical cancer treated with definitive radiation and chemotherapy. Patients were excluded if they received primary directed surgery, did not receive chemotherapy, had missing or incomplete radiation information, or had their Medicaid expansion status censored due to age < 40. A difference in difference (DID) analysis was performed to compare the uninsured rate and the rate of brachytherapy before and after expansion of Medicaid in states that did vs states that did not expand Medicaid. Multivariable analysis (MVA) for lack of insurance and completion of brachytherapy was adjusted for stage, race, facility type, median income, Charlson comorbidity and insurance (brachy analysis only).A total of 12,409 patients were included with a median age of 55. Most patients were treated at an academic center (50%) and 74% were white. Overall, 56% of patients lived in states that expanded Medicaid early (2010-2013, 21%) or late (2014, 35%). The proportion of patients without insurance significantly decreased in early and late expansion states (-3.2%, -6.6% respectively, P < 0.001) with no significant change in non-expansion states. The decrease in uninsured patients remained significant on multivariable analysis (DID MVA -5.2% early expansion, -6.8% late expansion, P < 0.05). The overall rate of brachytherapy usage increased in expansion states (+8.4% early, +5.0% late expansion, P < 0.001) and in states that did not expand coverage (+4.4%, P < 0.001). However, there was no increase in usage of brachytherapy in expansion states compared to non-expansion states on univariate or multivariate analysis (DID MVA 0.6% [-3.9-5.3] early expansion, -0.2% [-4.6-4.0] late expansion).Medicaid expansion and a subsequent decrease in the uninsured population did not increase the proportion of patients receiving brachytherapy as part of their definitive chemo-radiation for cervical cancer. Our study suggests that lack of insurance, while important, is not the only factor limiting access to standard of care treatment for cervical cancer. Further research into access and availability of brachytherapy is needed.S. Freije: None. E.M. Steele: None. S.E. Robertson: None. O. Ishaq: None. J.A. Holmes: None.

The predictive recurrence value of MTV-s as an 18F-FDG PET/CT index in patients with IIB-IVA cervical cancer

ABSTRACT Objectives: The aim of this study was to explore the predictive recurrence value of the PET/CT index and some clinical features in patients with IIB-IVA cervical cancer. Methods: This was a retrospective analysis of 84 patients with cervical cancer who underwent 18 F-FDG PET/CT scans before treatment. MTV-s is the sum of the metabolic volume of the primary cervical lesion (MTV-C) and the metabolic volume of the pelvic and abdominal paravascular metastatic lymph nodes (MTV-LN). We analyzed the relationships between clinical characteristics (age, FIGO stage, pathological pattern, degree of differentiation, tumor size, presence of LN metastasis), PET/CT index (SUVmax-C, SUVmax-LN, MTV-C, MTV-LN, MTV-s), and recurrence of cervical cancer using the chi-square test; the ROC curve was used to determine the PET/CT boundary parameters; and the COX proportional risk model was used for univariate and multivariate analysis of clinical features and the PET/CT index. The survival curve was drawn using the Kaplan–Meier method, comparing different groups by the log-rank test. Results: Eighty-four patients were included. During the observation period, 26 patients had tumor recurrence (31.0%). Univariate analysis showed that lymph node metastasis, lymph node SUVmax (SUVmax-LN), MTV-C, MTV-LN, and MTV-s were associated with PFS. MTV-s > 27.36 cm3 was an independent risk factor for PFS (P = 0.037). There were 41 patients with MTV-s > 27.36 cm3, and 19 of them had tumor recurrence (46.3%). There were 43 patients with MTV-s ≤ 27.36 cm3, 7 of whom had tumor recurrence (16.3%). Conclusion: MTV-s can predict recurrence in patients with stage IIB-IVA cervical cancer, with a critical value of 27.36 cm3. PET/CT can help clinicians judge the prognosis of patients more comprehensively.

The Impact of Histological Subtype on Survival Outcome of Patients with Stage IIB-IVA Cervical Cancer Who Received Definitive Radiotherapy.

The impact of histologic subtype on definitive radiotherapy for patients with locally advanced cervical cancer remains unclear. The aim of this retrospective analysis was to assess clinicopathological findings and clinical outcome by histological type in patients with stage IIB-IVA cervical cancer. Ninety-two patients with stage IIB-IVA [International Federation of Gynecology and Obstetrics (FIGO) 2008] cervical cancer, who underwent definitive radiotherapy between 2013 to 2018, were identified as eligible for this study. The clinical information of the eligible patients was obtained from medical records of our hospital. Seventy-eight patients underwent concurrent chemoradiotherapy, and the remaining 14 patients received radiotherapy alone. Of 92 patients, 83 had squamous cell carcinoma (SCC) and 9 had non-SCC histology. Progression-free survival (PFS) rate of patients with non-SCC was significantly worse than of those with SCC (2-year PFS: 62.0% vs. 12.5%, p = 0.0020), but overall survival (OS) rate did not statistically differ between the two subtypes (2-year OS: 82.4% vs. 62.5%, p = 0.2157). Pelvic failure-free (PFF) rate of patients with non-SCC histology was significantly worse than of those with non-SCC (2-year PFF; 88.2% vs. 25.0%, p < 0.0001). In univariate analysis, non-SCC histology was associated with PFS rate, although there was no association with OS rate. In multivariate analysis, non-SCC histology and lymph node metastasis were independent prognostic factors for shorter PFS. In patients with stage IIB-IVA cervical cancer who underwent definitive radiotherapy, patients with non-SCC showed significantly worse PFS rate than those with SCC.

Prognostic Significance of Tumor Regression Rate during Concurrent Chemoradiotherapy in Locally Advanced Cervix Cancer: Analysis by Radiation Phase and Histologic Type.

This study aimed to evaluate the prognostic significance of tumor regression rate according to radiation phase and histologic subtype in patients with locally advanced cervical cancer (LACC) treated with chemoradiation. We retrospectively reviewed the medical records of 398 patients with FIGO stage IIB-IVA cervical cancer treated with concurrent chemoradiotherapy (CCRT) between 2001 and 2019. Tumor response was assessed using serial magnetic resonance imaging (MRI) at three time points: pre-treatment, post-external beam radiotherapy (EBRT), and post-intracavitary radiotherapy (ICR). Tumor regression pattern according to histologic subtype and radiation phase (EBRT and ICR) was evaluated. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Of 398 patients, 44 patients had adenocarcinoma/adenosquamous carcinoma (AC/ASC) and 354 patients had squamous cell carcinoma (SCC). AC/ASC was associated with significantly worse PFS and OS than SCC (p < 0.001). AC/ASC had a relatively poorer regression rate in response to EBRT than SCC (p < 0.001), whereas there was no significant difference in overall tumor regression rate after completion of RT (EBRT and ICR) between the two histologic subtypes. Multivariable analysis demonstrated AC/ASC histology to be an independent prognostic factor of decreased PFS and OS. Moreover, tumor regression rate after completion of EBRT (post-EBRT tumor regression rate (EBRTregression ≤ 26%) and proportion of tumor regression during EBRT to overall tumor regression (EBRTproportion ≤ 40%) were independent predictors of poor survival in patients with LACC. Tumor regression pattern of LACC in response to CCRT differs according to histologic subtype. AC/ASC histology and poor tumor response to EBRT are independent prognostic factors for worse survival in patients with LACC. Further studies are needed to develop a CCRT protocol that is specialized for patients with AC/ASC.

Local Control and Overall Survival of Patients with Stage IIB–IVA Cervical Cancer after Definitive External Beam Chemoradiation and High-Dose-Rate Cobalt-60 Intracavitary Brachytherapy

The present study aimed to assess the local control and overall survival of patients with stage IIB–IVA cervical cancer after definitive external beam chemoradiation and high-dose-rate miniaturized Cobalt-60 (Co-60) intracavitary BT. This was a cross-sectional study that prospectively enrolled patients with cervical squamous cell carcinoma referred for BT as a part of their definitive treatment to Reza Radiotherapy & Oncology Center of Mashhad, Razavi Khorasan, Iran, between 2017 and 2018. The optimal dose of treatment was determined, and survival analysis was performed using the log-rank test at the level of p ≤ 0.05. A total of 65 patients were enrolled, and most of them had stage IIB (76.9%). With a median follow-up of 18 months, the 6-, 12-, 18-, and 24-month overall survival was 98%, 86%, 75%, and 50%, respectively. The optimal cutoff dose of high-risk clinical target volume (HR-CTV) was 85.06 gray (Gy). There was a trend in the reduction of survival in patients with higher stages and receiving lower doses to tumor; however, the results were not significant. Based on the results of this study, a minimum total dose of 85 Gy to high-risk clinical tumor volume is essential to achieve an optimal local control.

Racial and ethnic disparities over time in the treatment and mortality of women with gynecological malignancies

ObjectiveTo examine temporal trends in treatment and survival among black, Asian, Hispanic, and white women diagnosed with endometrial, ovarian, cervical, and vulvar cancer. MethodsUsing the National Cancer Database (2004–2014), we identified women diagnosed with endometrial, ovarian, cervical, and vulvar cancer. For each disease site, we analyzed race/ethnicity-specific trends in receipt of evidence-based practices. Professional societies' recommendations were used to define these practices. Using data from the Surveillance, Epidemiology, and End Results Program (2000–2009) we analyzed trends in 5-year survival. ResultsThroughout the study period black (64.8%) and Hispanic (68.3%) women were less likely to undergo lymphadenectomy for stage I ovarian cancer compared to Asian (79.5%) and white patients (74.6%). Black women were the least likely group to undergo lymphadenectomy in all periods. Among patients with stage II-IV ovarian cancer, 76.6% of white and Asian women received both surgery and chemotherapy, compared to 70.8% of black and 73.9% Hispanic women. Hispanic women with deeply invasive or high-grade stage I endometrial cancer underwent lymphadenectomy less frequently (74.5%) than all other groups (80.7%). Black women were less likely to have chemo-radiotherapy for stage IIB–IVA cervical cancer (75.6% versus 80.4% of all others). Black women were also less likely to have a surgical lymph node evaluation for vulvar cancer (58.8% versus 63.5% of all others). Among women diagnosed with ovarian, endometrial, and cervical cancer, black women had lower five-year survival than other groups. ConclusionSignificant racial disparities persist in the delivery of evidence-based care. Black women with ovarian, endometrial, and cervical cancer continue to experience higher cancer-specific mortality than other groups.

Application of extracorporeal extended field radiotherapy in locally advanced cervical cancer

Objective To investigate the application value of extracorporeal extended field radiotherapy in locally advanced cervical cancer. Methods A total of one hundred and twenty patients with stage IIB-IVA cervical cancer in the First Affiliated Hospital of Hebei North University from June 2012 to June 2014 were randomly divided into two groups: the control group and the observation group, each with 60 cases.The routine concurrent chemoradiotherapy was adopted in the control group.The observation group was treated with extracorporeal extended field radiotherapy combined with concurrent chemotherapy.The patients have been followed up for three years.The total efficacy rate, toxicity reaction, local progression free survival time (PFS) and survival rate of the two groups were compared. Results The total efficacy rate in the observation group was significantly higher than that of the control group (88.3%(53/60) vs.73.3%(44/60), χ2=4.357, P=0.037), while the incidences of toxicity reaction in the two groups were 18.3%(11/60) and 16.7%(10/60), the difference was not statistically significant (χ2=0.058, P=0.810), the percentages of I and II degree in the two groups were 3.4%(2/60) and 3.4%(2/60), the difference between the two groups was not statistically significant (Z=0.000, P=1.000). The PFS value in the observation group was significantly longer than that of the control group (25.6 months vs.13.8 months, χ2=25.624, P=0.000), and the survival rate in the observation group improved significantly (53.3%(32/60) vs.33.3%(20/60), the difference was statistically significant (χ2=4.887, P=0.027). Conclusion Extracorporeal extended field radiotherapy is safe and effective in the treatment of locally advanced cervical cancer. Key words: Extracorporeal extended field radiotherapy; Advanced cervical cancer; Efficacy rate; Toxicity reaction; Progression free survival; Survival rate

Predictors of distant relapse in patients with FIGO stage IIB-IVA cervical cancer treated with definitive radiotherapy.

To investigate the predictors of distant relapse in International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer patients treated with definitive radiotherapy (RT). The clinical data of 219 patients with FIGO stage IIB-IVA cervical cancer treated with definitive RT between January 1997 and December 2011 were retrospectively reviewed. The cumulative distant relapse, progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to investigate the predictors of distant relapse in patients. Following treatment with definitive RT, 61 of the 219 (27.9%) patients developed distant relapse with median PFS and OS rates of 9.9 and 32.8 months, and estimated five-year PFS and OS rates of 4.9% and 21.3%, respectively. Multivariate analysis revealed that pelvic node metastasis, pretreatment leukocytosis and pretreatment neutrophilia were significant predictors of distant relapse. The risk of developing distant relapse was found to be associated with the number of predictors that the patients displayed: the estimated five-year distant relapse rates of the patients with no predictors, one predictor and two predictors were 20.3%, 35.5% and 88.9%, respectively. Roughly 28% of patients with FIGO stage IIB-IVA cervical cancer developed distant relapse after definitive RT. Pelvic lymph node metastasis and pretreatment leukocytosis/neutrophilia are independent predictors of distant relapse.

Impact of sociodemographic and tumor characteristics vs guideline adherent care on stage IIB-IVA cervical cancer survival

Impact of sociodemographic and tumor characteristics vs guideline adherent care on stage IIB-IVA cervical cancer survival

Extraperitoneal lymph node dissection in locally advanced cervical cancer; the prognostic factors associated with survival.

Objective:Surgical staging was recently recommended for the decision of treatment in locally advanced cervical cancer. We aimed to investigate clinical outcomes as well as factors associated with overall survival (OS) in patients with locally advanced cervical cancer who had undergone extraperitoneal lymph node dissection and were managed according to their lymph node status.Material and Methods:The medical records of 233 women with stage IIb-IVa cervical cancer who were clinically staged and underwent extraperitoneal lymph node dissection were retrospectively reviewed. Paraaortic lymph node status determined the appropriate radiotherapeutic treatment field. Surgery-related complications and clinical outcomes were evaluated.Results:The median age of the patients was 52 years (range, 26-88 years) and the median follow-up time was 28.4 months (range, 3-141 months). Thirty-one patients had laparoscopic extraperitoneal lymph node dissection and 202 patients underwent laparotomy. The number of paraaortic lymph nodes extracted was similar for both techniques. Sixty-two (27%) of the 233 patients had paraaortic lymph node metastases. The 3-year and 5-year OS rates were 55.1% and 46.5%, respectively. The stage of disease, number of metastatic paraaortic lymph nodes, tumor type, and paraaortic lymph node status were associated with OS. In multivariate Cox regression analyses, tumor type, stage, and presence of paraaortic lymph node metastases were the independent prognostic factors of OS.Conclusion:Paraaortic lymph node metastasis is the most important prognostic factor affecting survival. Surgery would give hints about the prognosis and treatment planning of the patient.

Incidence of Histologically Proven Pelvic and Para-Aortic Lymph Node Metastases and Rate of Upstaging in Patients with Locally Advanced Cervical Cancer: Results of a Prospective Randomized Trial

Background: Surgical staging is associated with a significant rate of upstaging compared to clinical/radiological staging in patients with locally advanced cervical cancer. Objective: To analyze the stage-specific percentage of pelvic and para-aortic lymph node metastases and the upstaging ratio in a prospective randomized trial (Uterus-11). Methods: FIGO stage IIB-IVA cervical cancer patients were randomized to surgical staging (arm A) or to clinical staging and primary chemoradiation (arm B). Arm B patients underwent CT-guided biopsy of suspicious para-aortic lymph nodes. Confirmed para-aortic metastasis patients received extended-field radiation therapy. Results: A total of 234 patients were enrolled, including 120 (arm A) and 114 (arm B) treated per protocol. The groups were well balanced. Pelvic and para-aortic lymph node metastases were identified after surgical staging in 51 and 24% of patients, respectively (p < 0.001). Pelvic and para-aortic lymph node metastases were confirmed in 45 and 20% of IIB patients and in 71 and 37% of IIIB patients, respectively. Upstaging occurred in 39/120 (33%) in arm A and in 9/114 (8%) in arm B (p < 0.001). Conclusion: The histological results in both groups led to a considerable rate of upstaging. Oncological data from the Uterus-11 study may reveal whether modified therapy translates into a survival benefit.

Appliation of compound mylabris capsules combined with concurrent chemoradiotherapy in cervical carcinoma

Objective To observe the clinical efficacy and adverse reactions of compound mylabris capsules combined with concurrent chemoradiotherapy for patients with locally advanced cervical cancer. Methods From September 2013 to September 2014, we collected 80 patients with stage ⅡB-ⅣA cervical cancer who were admitted to Cancer Center of Affiliated People′s Hospital of Hubei University of Medicine. They were divided into the observation group (n=40) and control group (n=40) according to random number table. Patients of observation group were treated with compound mylabris capsules combined with chemo-radiotherapy, and patients of the control group were treated with the concurrent chemoradiotherapy alone. TP scheme of paclitaxel plus cisplatin was used in chemotherapy. Intensity-modulated radiation therapy (IMRT) and intracavitary brachytherapy was used in radiotherapy. The effective rates, Karnofsky Performance Status (KPS) scores, and recent adverse reactions in the two groups were compared. Results The short-time effective rates in the observation group and control group were 97.5% and 95.0% respectively, with no significant difference (χ2=0.346, P=0.556). The grade Ⅲ-Ⅳ adverse reactions in the observation group and control group included leucopenia (80.0% vs. 95.0%), lower hemoglobin (22.5% vs.45.0%), thrombocytopenia (60.0% vs. 82.5%), radioactive urocystitis (5.0% vs. 30.0%), radioactive proctitis (10.0% vs. 30.0%), with significant differences (χ2=4.114, P=0.043; χ2=4.528, P=0.033; χ2=4.943, P=0.026; χ2=8.658, P=0.003; χ2=5.000, P=0.025). The KPS score in the observation group was higher than that in the control group (90 vs. 70), with significant difference (Z=4.523, P=0.000). Conclusion The clinical efficacy of compound mylabris capsules combined with concurrent chemoradiotherapy and chemoradiotherapy alone for patients with locally advanced cervical cancer are similar. Compound mylabris capsules can reduce the rates of adverse reactions such as leucopenia, lower hemoglobin, thrombocytopenia, radioactive urocystitis and radioactive proctitis, and can improve KPS score, which plays a role of reliving toxicity. Key words: Uterine cervical neoplasms; Radiotherapy; Chemotherapy, adjuvant; Drug therapy

Prognostic Value of the Sum of Metabolic Tumor Volume of Primary Tumor and Lymph Nodes Using 18F-FDG PET/CT in Patients With Cervical Cancer.

This is an observational study to determine the most relevant parameter of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting recurrence in cervical cancer.Fifty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer who underwent pretreatment 18F-FDG PET/CT were enrolled. PET parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of both primary tumor and pelvic and/or para-aortic lymph nodes were analyzed. SUVmax-S was defined as the sum of the SUVmax of primary tumor and the higher SUVmax of either pelvic or para-aortic lymph nodes. MTV-S was defined as the sum of the MTV of primary tumor and pelvic and para-aortic lymph nodes. TLG-S was calculated in the same way as MTV-S. We evaluated the relationship between these PET parameters and recurrence-free survival (RFS).Univariate analysis revealed that higher FIGO stage (hazard ratio [HR] = 5.61, 95% confidence interval [CI]: 1.68–18.68, P = 0.005), lymph node metastasis (HR = 3.42, 95% CI: 1.08–10.84, P = 0.037), MTV of primary tumor >47.81 cm3 (HR = 6.20, 95% CI: 1.35–28.48, P = 0.019), TLG of primary tumor >215.02 (HR = 11.82, 95% CI: 1.52–91.96, P = 0.018), MTV-S > 59.01 cm3 (HR = 8.24, 95% CI: 1.80–37.77, P = 0.007), and TLG-S > 224.15 (HR = 13.09, 95% CI: 1.68–101.89, P = 0.014) were associated with RFS. In multivariate analysis, FIGO stage (HR = 4.87, 95% CI: 1.38–17.18, P = 0.014) and MTV-S > 59.01 cm3 (HR = 7.37, 95% CI: 1.54–35.16, P = 0.012) were determined to be independent predictive factors for RFS.Our preliminary results reveal that MTV-S is an independent prognostic factor for RFS in patients with cervical cancer treated by definitive chemoradiotherapy.

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients—Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group

The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.

Effect of changes in treatment practice on survival for cervical cancer: results from a population-based study in Manitoba, Canada.

BackgroundResults from clinical trials in the 1990s led to changes in the recommended treatment for the standard therapy for stage IIB-IVA cervical cancer from radiotherapy alone to chemo-radiotherapy. We conducted the first population-based study in Canada to investigate temporal treatment patterns for cervical cancer and long-term survival in relation to these changes in the treatment guidelines.MethodsDetailed information on stage and treatment for 1085 patients diagnosed with cervical cancer in 1984–2008 and identified from the population-based Manitoba Cancer Registry (MCR) in Canada was obtained from clinical chart review and the MCR. Factors associated with receiving guideline treatment were identified using logistic regression. All cause and cervical cancer specific survival were compared in patients who were and were not treated as recommended in the guidelines, using Cox proportional hazards models.ResultsThe median follow-up time was 6.4 years (range: 0.05–26.5 years). The proportion of women who received guideline treatment was 79 % (95 % confidence interval [CI]: 76–81 %). However, the likelihood of being treated according to the guidelines over time was modified by age (p < 0.0001) and tumour stage at diagnosis (p = 0.002). Women who were treated according to the guidelines after the change in recommended clinical practice (1999–2008) had a significantly lower risk of death from all causes and from cervical cancer. This was driven by lower mortality rates in cases with stage IIB-IVA tumours (all causes of death: hazard ratio [HR] = 0.60, 95 % CI: 0.43–0.82, p = 0.002; cervical cancer related death: HR = 0.64, 95 % CI: 0.44–0.93, p = 0.02).ConclusionsThe management of cervical cancer patients in Manitoba, Canada was in good agreement with treatment guidelines although reasons for departure from the guideline recommendations could not be examined further due to lack of data. Treatment of stage IIB-IVA cervical cancers with recommended concurrent chemo-radiotherapy, which is now standard practice, was associated with substantially increased survival, although the effect of changes in clinical practice including maintenance of haemoglobin levels on improved survival cannot be ruled out as a contributing factor.