Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Combined pretreatment with 18F-FDG PET/CT and Comet assay guides the concurrent chemoradiotherapy of locally advanced cervical cancer: study protocol for a randomized controlled trial

Authors: Shengjun Ji, Qunchao Hu, Jiahao Zhu, Jie Chen, Qingqing Chen, Zhengcao Liu, Chen Shen, Ru Yang, Haoyao Sun, Jinchang Wu, Ke Gu

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

Cisplatin-based chemoradiation is the standard of care for patients with locally advanced cervical cancer. Nevertheless, an increasing number of radio-resistant tumors still recur.

Methods and design

Three hundred cervical cancer patients with FIGO stages IB2–IVA and no para-aortic lymphadenopathy (> 10 mm) will be enrolled. All patients will be randomly divided into four arms to receive either (1) intensity modulated radiation therapy (IMRT), (2) RapidArc, (3) positron emission tomography/computed tomography (PET/CT) with F-18 fluorodeoxyglucose (FDG), or (4) Comet assay-guided IMRT, PET/CT, and Comet assay-guided RapidArc. All patients will receive definitive radiotherapy consisting of external beam whole pelvic radiation therapy and high-dose rate intracavitary brachytherapy. Cisplatin 30 mg/m2 weekly will be administered concurrently for five courses. Two to four cycles of TP (Taxol 135 mg/m2, D1, and DDP 75 mg/m2, D1–3) sequential chemotherapy will be performed according to MRI or PET/CT after cisplatin-based chemoradiation. The primary outcome measure is progression-free survival, and the second outcome measures are overall survival and time to progression.

Discussion

RapidArc has an obvious advantage in improving the degree of target coverage, improving organs at risk, sparing healthy tissue, and significantly reducing the treatment time. FDG-PET/CT can increase the agreement between biopsies and delineated tumor volume and has the potential to positively impact the course of treatment. The Comet assay is attractive as a potential clinical test of tumor radiosensitivity. During radiotherapy, accurately defining disease areas is critical to avoid the unnecessary irradiation of normal tissue. Based on FDG-PET/CT and Comet assay, higher doses can be safely delivered to accurate tumor volumes, while the doses to the bladder and rectum are relatively low.

Trial registration

ClinicalTrials.​gov Protocol Registration and Results System Receipt Release Date: May 21, 2017 – Retrospectively registered. NCT03163979.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
Nogueira-Rodrigues A, Moralez G, Grazziotin R, Carmo CC, Small IA, Alves FV, Mamede M, Erlich F, Viegas C, Triginelli SA. Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer. Cancer. 2014;120:1187–93.CrossRefPubMed
3.
Tharavichitkul E, Pinitpatcharalerd A, Lorvidhaya V, Kamnerdsupaphon P, Pukanhaphan N, Sukthomya V, Chitapanarax I, Galalae R. Impact of incomplete plan to treatment results of concurrent weekly cisplatin and radiotherapy in locally advanced cervical cancer. J Radiat Res. 2011;52:9–14.CrossRefPubMed
4.
Zhai D-Y, Yin Y, Gong G-Z, Liu T-H, Chen J-H, Ma C-S, Lu J. RapidArc radiotherapy for whole pelvic lymph node in cervical cancer with 6 and 15 MV: a treatment planning comparison with fixed field IMRT. J Radiat Res. 2013;54:166–73.CrossRefPubMed
5.
Cozzi L, Dinshaw KA, Shrivastava SK, Mahantshetty U, Engineer R, Deshpande DD, Jamema S, Vanetti E, Clivio A, Nicolini G. A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy. Radiother Oncol. 2008;89:180–91.CrossRefPubMed
6.
Legge F, Chiantera V, Macchia G, Fagotti A, Fanfani F, Ercoli A, Gallotta V, Morganti AG, Valentini V, Scambia G. Clinical outcome of recurrent locally advanced cervical cancer (LACC) submitted to primary multimodality therapies. Gynecol Oncol. 2015;138(1):83–8.CrossRefPubMed
7.
Rose PG, Java J, Whitney CW, Stehman FB, Lanciano R, Thomas GM, Di Silvestro PA. 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. J Clin Oncol. 2015;33(19):2136–42.CrossRefPubMedPubMedCentral
8.
Shi X, Meng X, Sun X, Xing L, Yu J. PET/CT imaging-guided dose painting in radiation therapy. Cancer Lett. 2014;355:169–75.CrossRefPubMed
9.
Bowman KJ, Al-Moneef MM, Sherwood BT, Colquhoun AJ, Goddard JC, Griffiths T, Payne D, Singh S, Butterworth PC, Khan MA. Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo. Int J Cancer. 2014;134:1102–11.CrossRefPubMed
10.
Marples B, Longhurst D, Eastham AM, West C. The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines. Br J Cancer. 1998;77(7):1108–14.CrossRefPubMedPubMedCentral
11.
Alongi F, Fersino S, Levra NG, Mazzola R, Ricchetti F, Fiorentino A, Ruggieri R, Malfatti V, Cavalleri S, Salgarello M. Impact of 18F-choline PET/CT in the decision-making strategy of treatment volumes in definitive prostate cancer volumetric modulated radiation therapy. Clin Nucl Med. 2015;40:e496–500.CrossRefPubMed
12.
13.
14.
Miccò M, Vargas HA, Burger IA, Kollmeier MA, Goldman DA, Park KJ, Abu-Rustum NR, Hricak H, Sala E. Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer. Euro J Radiol. 2014;83:1169–76.CrossRef
15.
Ramlov A, Kroon PS, Jürgenliemk-Schulz IM, De Leeuw AA, Gormsen LC, Fokdal LU, Tanderup K, Lindegaard JC. Impact of radiation dose and standardized uptake value of (18) FDG PET on nodal control in locally advanced cervical cancer. Acta Oncol. 2015;54:1567–73.CrossRefPubMed
16.
Kidd EA, Siegel BA, Dehdashti F, Grigsby PW. The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival. Cancer. 2007;110:1738–44.CrossRefPubMed
17.
Beriwal S, Kannan N, Sukumvanich P, Richard SD, Kelley JL, Edwards RP, Olawaiye A, Krivak TC. Complete metabolic response after definitive radiation therapy for cervical cancer: patterns and factors predicting for recurrence. Gynecol Oncol. 2012;127:303–6.CrossRefPubMed
18.
Kidd EA, Siegel BA, Dehdashti F, Rader JS, Mutic S, Mutch DG, Powell MA, Grigsby PW. Clinical outcomes of definitive intensity-modulated radiation therapy with fluorodeoxyglucose–positron emission tomography simulation in patients with locally advanced cervical cancer. Int J Radiat Oncol. 2010;77:1085–91.CrossRef
19.
Goutham HV, Mumbrekar KD, Vadhiraja BM, Fernandes DJ, Sharan K, Parashiva GK, Kapaettu S, Sadashiva SRB. DNA double-strand break analysis by γ-H2AX foci: a useful method for determining the overreactors to radiation-induced acute reactions among head-and-neck cancer patients. Int J Radiat Oncol. 2012;84:e607–12.CrossRef
20.
Greulich-Bode K, Zimmermann F, Müller W-U, Pakisch B, Molls M, Würschmidt F. Clinical, molecular-and cytogenetic analysis of a case of severe radio-sensitivity. Curr Genomics. 2012;13:426.CrossRefPubMedPubMedCentral
21.
Gunasekarana V, Raj GV, Chand P. A comprehensive review on clinical applications of comet assay. J Clin Diagno Res. 2015;9:GE01.
22.
Santoro R, Ferraiuolo M, Morgano GP, Muti P, Strano S. Comet assay in cancer chemoprevention. Methods Mol Biol. 2016;1379:99–105.CrossRefPubMed
23.
Osaki JH, Espinha G, Magalhaes YT, Forti FL. Modulation of RhoA GTPase activity sensitizes human cervix carcinoma cells to γ-radiation by attenuating DNA repair pathways. Oxid Med Cell Longev. 2016;2016:6012642.CrossRefPubMed
24.
Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol. 1995;31:1341–6.CrossRef
25.
Lim K, Small W, Portelance L, Creutzberg C, Jürgenliemk-Schulz IM, Mundt A, Mell LK, Mayr N, Viswanathan A, Jhingran A. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer. Int J Radiat Oncol. 2011;79:348–55.CrossRef
26.
Forrest J, Presutti J, Davidson M, Hamilton P, Kiss A, Thomas G. A dosimetric planning study comparing intensity-modulated radiotherapy with four-field conformal pelvic radiotherapy for the definitive treatment of cervical carcinoma. Clin Oncol. 2012;24:e63–70.CrossRef
27.
GIBB, R. & MASSEY, J. B., 1980. Radium dosage: SI units andthe Manchester System. British Journal of Radiology. 53,1100–1101.
28.
29.
Palma D, Vollans E, James K, Nakano S, Moiseenko V, Shaffer R, McKenzie M, Morris J, Otto K. Volumetric modulated arc therapy for delivery of prostate radiotherapy: comparison with intensity-modulated radiotherapy and three-dimensional conformal radiotherapy. Int J Radiat Oncol. 2008;72:996–1001.CrossRef
30.
Lin LL, Mutic S, Low DA, LaForest R, Vicic M, Zoberi I, Miller TR, Grigsby PW. Adaptive brachytherapy treatment planning for cervical cancer using FDG-PET. I Int J Radiat Oncol. 2007;67:91–6.CrossRef
31.
Zhao J, Guo Z, Zhang H, Wang Z, Song L, Ma J, Pei S, Wang C. The potential value of the neutral comet assay and γH2AX foci assay in assessing the radiosensitivity of carbon beam in human tumor cell lines. Radio Oncol. 2013;47:247–57.CrossRef
Metadata
Title
Combined pretreatment with 18F-FDG PET/CT and Comet assay guides the concurrent chemoradiotherapy of locally advanced cervical cancer: study protocol for a randomized controlled trial
Authors
Shengjun Ji
Qunchao Hu
Jiahao Zhu
Jie Chen
Qingqing Chen
Zhengcao Liu
Chen Shen
Ru Yang
Haoyao Sun
Jinchang Wu
Ke Gu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2800-7

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Effectiveness of a psycho-educational intervention to prevent postpartum parental distress and enhance infant well-being: study protocol of a randomized controlled trial

Methodology

Are randomised controlled trials positivist? Reviewing the social science and philosophy literature to assess positivist tendencies of trials of social interventions in public health and health services

Research

Financial management of large, multi-center trials in a challenging funding milieu

Study protocol

Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the gastroduodenal artery stump for prevention of pancreatectomy hemorrhage

Study protocol

Follow-up study regarding the medium-term effectiveness of the home-visiting program “Pro Kind” at age 7 years: study protocol for a randomized controlled trial

Study protocol

Feasibility and acceptability of PrE-operative Physical Activity to improve patient outcomes After major cancer surgery: study protocol for a pilot randomised controlled trial (PEPA Trial)