Prediction of Progression-Free Survival and Response to Paclitaxel Plus Carboplatin in Patients With Recurrent or Advanced Cervical Cancer

Purpose To determine whether plasma human papillomavirus (HPV) DNA predates clinical recurrence and compare its accuracy with 3-month fluorodeoxyglucose positron emission tomography (FDG-PET) in locally advanced cervical cancer. Methods This prospective multicenter study accrued 23 women with stage IB to IVA cervical cancer planned for definitive chemoradiation therapy (CRT). Plasma HPV DNA was measured serially by digital polymerase chain reaction, and FDG-PET was performed at 3 months post-CRT. Results Of the 19 women with HPV+ cervical cancer included in this analysis, 32% were stage IB, 58% IIB, and 10% IIIB/IVA. Median follow-up was 24 months (range, 18 to 30 months). All patients had detectable plasma HPV DNA before treatment. Six patients had detectable plasma HPV DNA at the end of CRT, and three of them developed metastases at 3 months. Of the 13 patients with undetectable plasma HPV DNA at end of CRT, to date, only one has developed recurrence. Six of those 13 patients had a positive 3-month FDG-PET with no definite residual disease on subsequent imaging or clinical examination to date, and four of these six had undetectable plasma HPV DNA at 3 months. Patients with undetectable plasma HPV DNA at end of CRT had significantly higher 18-month progression-free survival than those with detectable plasma HPV DNA (92% v 50%; P = .02). The area under the receiver operating characteristic curve (accuracy) of 3-month plasma HPV DNA and 3-month FDG-PET imaging for predicting recurrence at 18 months were 77% and 60%, respectively ( P = .008). Conclusion Detectable plasma HPV DNA at end of CRT predates the clinical diagnosis of metastases and is associated with inferior progression-free survival. Moreover, 3-month plasma HPV DNA level is more accurate than 3-month FDG-PET imaging in detecting residual disease. The clinical utility of plasma HPV DNA detection for guiding adjuvant/salvage therapy should be evaluated in future studies.

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A prospective study on neoadjuvant chemoradiotherapy plus nimotuzumab followed by surgery for patients with advanced cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17000 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17000-e17000

Author(s):

Heming Lu ◽

Jinming Yu ◽

Yuying Wu ◽

Xu Liu ◽

Hailan Jiang ◽

...

Keyword(s):

Cervical Cancer ◽

Survival Rate ◽

Residual Disease ◽

Neoadjuvant Chemoradiotherapy ◽

Progression Free Survival ◽

Intraepithelial Neoplasia ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Loss Of Appetite ◽

A Prospective Study

e17000 Background: This study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy plus nimotuzumab followed by surgery for advanced cervical cancer. Methods: The inclusion criteria of this study were as follows: age: 18-75 years old; ECOG 0-1; FIGO stages IB2-IIIB; not eligible for surgery. IMRT with a total dose of 50-54 Gy was delivered to the tumor and the whole uterus, and 45-48.6 Gy to the high-risk regions. Weekly cisplatin or nedaplatin was administered concurrently with IMRT. Weekly nimotuzumab was given for 6 cycles. Patients were then assessed for clinical tumor response and operability. For those who were candidates for surgery, radical hysterectomy and pelvic lymph node dissection were performed 5-6 weeks after the completion of neoadjuvant therapy. Results: Twenty-eight patients were enrolled. Stage distributions were as follows: IB2, 3 pts; IIA, 5 pts; IIB, 16 pts; IIIA, 2 pts; IIIB, 2 pts. Twenty six (92.8%) patients completed ≥ 5 cycles of chemotherapy, and all completed ≥5 cycles of nimotuzumab. Complete clinical response and partial response were found in 8 patients (28.5%) and 20 patients (71.5%), respectively. Four patients were not eligible for surgery and 2 candidates refused surgery. They were not included in this analysis. Radical surgery was performed for the remaining 22 patients. Among them, 8 (36.4%) had complete pathology response, 9 (40.9%) presented with persistent atypical cells or cervical intraepithelial neoplasia, and 5 (22.7%) presented with macroscopic and/or microscopic residual disease. Median follow-up was 22 months (range, 5-39 months). The 2-year locoregional control rate, progression-free survival rate, distant metastasis-free survival rate, and overall survival rate were 95.0%, 85.2%, 84.0%, and 90.0%, respectively. Acute toxicity profiles were mainly manifested as marrow suppression, nausea, diarrhea, and loss of appetite. They were mild in general and easily manageable. Chronic toxicities were mainly limited to grade 1. No severe late toxicities were observed Conclusions: This treatment approach is highly effective and safe in advanced cervical cancer. Further studies are warranted to confirm the findings. Clinical trial information: NCT01938105.

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MRI Radiomic Features: A Potential Biomarker for Progression-Free Survival Prediction of Patients With Locally Advanced Cervical Cancer Undergoing Surgery

Frontiers in Oncology ◽

10.3389/fonc.2021.749114 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mengting Cai ◽

Fei Yao ◽

Jie Ding ◽

Ruru Zheng ◽

Xiaowan Huang ◽

...

Keyword(s):

Cervical Cancer ◽

Validation Cohort ◽

Locally Advanced ◽

Progression Free Survival ◽

Risk Groups ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Training Cohort ◽

Clinical Model ◽

Locally Advanced Cervical Cancer

ObjectivesTo investigate the prognostic role of radiomic features based on pretreatment MRI in predicting progression-free survival (PFS) of locally advanced cervical cancer (LACC).MethodsAll 181 women with histologically confirmed LACC were randomly divided into the training cohort (n = 126) and the validation cohort (n = 55). For each patient, we extracted radiomic features from whole tumors on sagittal T2WI and axial DWI. The least absolute shrinkage and selection operator (LASSO) algorithm combined with the Cox survival analysis was applied to select features and construct a radiomic score (Rad-score) model. The cutoff value of the Rad-score was used to divide the patients into high- and low-risk groups by the X-tile. Kaplan–Meier analysis and log-rank test were used to assess the prognostic value of the Rad-score. In addition, we totally developed three models, the clinical model, the Rad-score, and the combined nomogram.ResultsThe Rad-score demonstrated good performance in stratifying patients into high- and low-risk groups of progression in the training (HR = 3.279, 95% CI: 2.865–3.693, p < 0.0001) and validation cohorts (HR = 2.247, 95% CI: 1.735–2.759, p < 0.0001). Otherwise, the combined nomogram, integrating the Rad-score and patient’s age, hemoglobin, white blood cell, and lymph vascular space invasion, demonstrated prominent discrimination, yielding an AUC of 0.879 (95% CI, 0.811–0.947) in the training cohort and 0.820 (95% CI, 0.668–0.971) in the validation cohort. The Delong test verified that the combined nomogram showed better performance in estimating PFS than the clinical model and Rad-score in the training cohort (p = 0.038, p = 0.043).ConclusionThe radiomics nomogram performed well in individualized PFS estimation for the patients with LACC, which might guide individual treatment decisions.

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Comparison of Nedaplatin- and Cisplatin-Based Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer Patients: A Propensity Score Analysis

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001265 ◽

2018 ◽

Vol 28 (5) ◽

pp. 1029-1037

Author(s):

Ping Li ◽

Rui Zhang ◽

Zhihua Nie ◽

Mengjuan Long ◽

Gong Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Propensity Score ◽

Concurrent Chemoradiotherapy ◽

Propensity Score Analysis ◽

Locally Advanced ◽

Progression Free Survival ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

Score Analysis

PurposeThe aim of this study was to evaluate the efficacy of using nedaplatin to replace cisplatin for concurrent chemoradiotherapy (CCRT) in patients with newly diagnosed locally advanced cervical cancer.MethodsThe medical records of 155 patients with cervical cancer who had undergone CCRT with cisplatin (n = 85) or nedaplatin (n = 70) between January 2012 and January 2017 were retrospectively reviewed. Propensity score analysis with 1:1 matching with the nearest neighbor matching method was performed to assess response rates, progression-free survival, overall survival, and toxicity between 2 groups.ResultsPropensity score matching identified 63 patients in each group. After matching, compared with patients treated with cisplatin-based concurrent chemoradiotherapy (CisRT), we found that patients treated with nedaplatin-based concurrent chemoradiotherapy (NedaRT) had a significant higher recurrence rate (25.4% vs 42.9%; P = 0.04). In addition, the 3-year progression-free survival rate for NedaRT group was also worse than that for the CisRT group (52.2% vs 63.4%, P = 0.03). There was no difference in the overall response rates between the CisRT and NedaRT groups (87.3% and 90.5%, respectively; P = 0.57). The rates of 3-year overall survival and grades 3 to 4 toxicities were similar between the 2 groups.ConclusionsThe clinical outcome of this cohort of patients with locally advanced cervical cancer treated with CCRT did in no way provide support for the use of nedaplatin in place of cisplatin in chemoradiation and demonstrated no equivalence of the 2 drugs. Cautions should be taken for the replacement among platinum complexes in cancer treatment.

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Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2014.57.7122 ◽

2015 ◽

Vol 33 (19) ◽

pp. 2136-2142 ◽

Cited By ~ 52

Author(s):

Peter G. Rose ◽

James Java ◽

Charles W. Whitney ◽

Frederick B. Stehman ◽

Rachelle Lanciano ◽

...

Keyword(s):

Cervical Cancer ◽

Prognostic Factors ◽

Gynecologic Oncology ◽

Locally Advanced ◽

Progression Free Survival ◽

Pelvic Recurrence ◽

Gynecologic Oncology Group ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer

Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes.

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Therapeutic efficacy of epidermal growth factor receptor monoclonal antibody combined with concurrent chemoradiotherapy in treatment of locally advanced cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17012 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17012-e17012

Author(s):

Wenli Chen ◽

Tao Li ◽

Wei Zhang ◽

Jialin Yang ◽

Jian Wang ◽

...

Keyword(s):

Cervical Cancer ◽

Concurrent Chemoradiotherapy ◽

Locally Advanced ◽

Survival Rates ◽

Progression Free Survival ◽

Control Group ◽

Study Group ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Locally Advanced Cervical Cancer

e17012 Background: There are few studies about epidermal growth factor receptor monoclonal antibody nimotuzumab for the treatment of locally advanced cervical cancer. We aimed to assess the therapeutic efficacy and analyse prognostic factors of chemoradiotherapy combined with nimotuzumab in cervical cancer (stage IIB-IVA) . Methods: We retrospectively analyzed 23 patients with locally advanced cervical cancer(stage IIB-IVA) ,who received concurrent chemoradiotherapy combined with nimotuzumab from 2012 to 2014 (the study group) ,and 30 patients with the similar baseline characteristics who received concurrent chemoradiotherapy alone (the control group). The overall response rates, 5-year overall survival rates, progression-free survival and acute adverse events of the two groups were compared .Multivariate prognostic analysis was performed by a Cox proportional hazards model. Results: The median follow-up time were 46 months (IQR 16-60) in the study group and 42 months (2-60) in the control group.The overall response rates were 87% and 73.3% (P = 0.384) . The 5-year overall survival rates were 63.6% and 36.1% (hazard ratio 2.208,95% CI 0.878-5.557,P = 0.092) .The median progression-free survival in the study group was not achieved (95%CI 9-55) versus 27 months (1-60) in the control group (hazard ratio 2.635, 95% CI 1.030-6.737, P= 0.043).Multivariate prognostic analysis indicated that stage and whether to be combined with nimotuzumab were the influential factors for progression-free survival time.Adverse events were similar between groups.The most common grade 3 or 4 adverse events during treatment in the study group versus the control group were leucopenia(9 [39%] vs 11 [36%]),thrombocytopenia (3 [13%] vs 6 [20%]),anaemia (4 [17%] vs 4 [13%]). Conclusions: Concurrent chemoradiotherapy combined with nimotuzumab in the treatment can improve the progression-free survival time of advanced cervical cancer, while not increasing the incidence of adverse reactions.However, because of the small size of sample in this research, these findings suggest that it is necessary to perform a prospective study with expanded sample size.

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Human papillomavirus status in advanced cervical cancer: predictive and prognostic significance for curative radiation treatment

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200503000-00015 ◽

2005 ◽

Vol 15 (2) ◽

pp. 278-284 ◽

Cited By ~ 3

Author(s):

K. Lindel ◽

P. Burri ◽

H. U. Studer ◽

H. J. Altermatt ◽

R. H. Greiner ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Human Papillomavirus ◽

Progression Free Survival ◽

Hpv Infection ◽

Radiation Response ◽

Advanced Cervical Cancer ◽

Free Survival ◽

E2 Gene ◽

Local Progression

Human papillomavirus (HPV) infection plays a major role in oncogenesis of squamous cell carcinoma of the cervix. This study was performed to investigate if HPV status and E2 gene integrity are prognostic parameters for clinical outcome and predictive for radiation response. Forty women with locally advanced cervical cancer treated with curative radiotherapy were analyzed for HPV infection and E2 gene integrity by multiplex polymerase chain reaction. Statistical analyses were performed for overall survival, disease-free survival (DFS), local progression-free survival, and treatment response (clinical complete remission). Twenty-eight (70%) of 40 carcinomas were HPV positive. The only significant factor for a better overall survival, DFS, and local progression-free survival was HPV positivity (P < 0.02, P = 0.02, and P < 0.05, log-rank, respectively). HPV-positive tumors had a significantly better clinical complete remission (67% vs 33%, P = 0.04, Fisher's exact test). An intact E2 gene region showed a trend for a better DFS (P = 0.1, log-rank). This study reveals HPV as an independent prognostic parameter for outcome and radiation response. Integration of the virus genome into host cell DNA might be a molecular target to determine the treatment response of HPV-positive cancers.

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Endostar, an Anti-angiogenesis Inhibitor, Combined with Chemoradiotherapy for Locally Advanced Cervical Cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504021x16318716607908 ◽

2021 ◽

Author(s):

Heming Lu ◽

Yuying Wu ◽

Xu Liu ◽

Huixian Huang ◽

Hailan Jiang ◽

...

Keyword(s):

Cervical Cancer ◽

Locally Advanced ◽

Angiogenesis Inhibitor ◽

Progression Free Survival ◽

Late Toxicity ◽

Advanced Cervical Cancer ◽

Term Survival ◽

Free Survival ◽

Locally Advanced Cervical Cancer ◽

The Impact

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an anti-angiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar(CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT)and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for 2 cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116patientswere enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1-and 2-year PFS were 91.4% vs. 82.1% and 80.8% vs. 63.5%（p=0.091）, respectively. The1-and 2-year distance metastasis-free survival （DMFS）were92.7% vs. 81.1% and 86.0% vs. 65.1%（p=0.031）, respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS), compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm whenVEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

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Safety and Efficacy of Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Radical Surgery Alone in Locally Advanced Cervical Cancer Patients

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000658 ◽

2016 ◽

Vol 26 (4) ◽

pp. 722-728 ◽

Cited By ~ 6

Author(s):

Lin Gong ◽

Jia-Wen Zhang ◽

Ru-Tie Yin ◽

Ping Wang ◽

Hui Liu ◽

...

Keyword(s):

Cervical Cancer ◽

Neoadjuvant Chemotherapy ◽

Adverse Effects ◽

Radical Surgery ◽

Locally Advanced ◽

Progression Free Survival ◽

Advanced Cervical Cancer ◽

Free Survival ◽

Safety And Efficacy ◽

Locally Advanced Cervical Cancer

ObjectivesThis study aimed to evaluate the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with locally advanced cervical cancer (LACC).MethodsEight hundred patients with LACC received either NACT followed by RS (NACT–RS) or RS alone. The primary outcome measures assessed the efficacy and adverse effects of NACT. Secondary outcome measures compared the preoperative clinical stage to the postoperative pathologic stage in NACT–RS and RS patients, assessed intraoperative and postoperative complications, including the adverse effects of postoperative radiotherapy and radiochemotherapy, and estimated the 5-year progression-free survival and 5-year overall survival.ResultsThe clinical response to NACT was 89.54%. Patients in the NACT–RS group had lower preoperative hemoglobin levels (115.20 vs 122.04 g/L, P < 0.001), a longer operative time (mean, 233.66 vs 224.37 minutes, P = 0.008), more intraoperative bleeding (750.34 vs 684.41 mL, P = 0.011), a shorter duration of catheter use (mean, 29.84 vs 32.14 days, P = 0.036), and a lower incidence of postoperative complications (7.30% vs 13.62%, P = 0.002) and postoperative radiotherapeutic and radiochemotherapeutic adverse effects (3.16% vs 4.63%, P < 0.001) compared to patients in the RS group. The 5-year progression-free survival and 5-year overall survival were 80.30% and 81.10% in the NACT–RS group and 81.00% and 78.50% in the RS group (P > 0.05). Pathological poor differentiation, nonsquamous cell carcinoma, parametrial invasion, positive pelvic lymph node, and lymphovascular invasion (P < 0.05) were independent risk factors for recurrence.ConclusionsNeoadjuvant chemotherapy may reduce RS-associated complications and postoperative radiotherapeutic and radiochemotherapeutic adverse effects in Chinese patients with LACC.

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