Study on Adaptive Radiotherapy and Multimodal Information of Cervical Cancer Assisted by Artificial Intelligence

NCT04022018 | Unknown

• 1 other identifier: hkuszh2019119
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

The standard treatment for non-operative cervical cancer is concurrent external radiation therapy and chemotherapy followed by brachytherapy. During the period of radiotherapy, organ movement and tumor shrinkage may lead to insufficient or excessive radiation dose for the tumor and organs at risk. Adaptive radiotherapy can use images information acquired during treatment as feedback to reduce errors. Total 122 cases of cervical cancer with stage IB2-IVA will be randomly enrolled. Concurrent external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of control group patients. Concurrent adaptive external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of experimental group patients. CT repositioning will be performed after 15fractions of external radiotherapy, then new target volume will be contoured and new radiotherapy plan will be formulated with the assistance of artificial intelligence program. New radiotherapy plan will be performed from the 17th fraction external radiotherapy. Information on side effects, survival, dosimetry, imaging, clinical features, and cost-effectiveness will be collected. The statistical analysis is as follows, First is the difference in grade 3 side effects between the two groups. Second is 2-year PFS and OS differences between the two groups. Third is relationship between dosimetric differences and prognosis. Fourth one is to analyze the prognostic and predictive factors of adaptive radiotherapy from the patient's clinical characteristics, Positron emission tomography-computed tomography(PET/CT), Magnetic Resonance Imaging(MRI) and other multimodal information. Fifth is cost-benefit analysis of Artificial Intelligence(AI).

Conditions

Cervical Cancer; Radiotherapy Side Effect; Biomarker; Artificial Intelligence

Keywords

cervical cancer; adaptive radiotherapy; side effects

Outcome Measures

Primary Outcomes (1)

• the difference in grade 3 side effects between the two groups

  Hematologic toxicity, bladder and rectal radiotherapy toxicity were recorded according to the evaluation criteria of common adverse events (CTCAE version 4.03).

  The acute radiotherapy reaction occur from the first day to 90 days after the end of radiotherapy, and the late radiotherapy reaction occur 90 days after radiotherapy.

Secondary Outcomes (6)

• 2-year PFS differences between the two groups

  2-year PFS

• 2-year OS differences between the two groups

  2-year OS

• the correlation between physical dosimetry differences and prognosis

  correlation between physical dosimetry differences and 2year PFS

• the predictive factors for the response rate of concurrent chemoradiotherapy for cervical cancer

  3 months after radiotherapy

• the prognostic factors for the 2-year overall survival rate of patients with cervical cancer after concurrent chemoradiotherapy

  2 years after radiotherapy

Study Arms (2)

Adaptive radiotherapy group

EXPERIMENTAL

Concurrent adaptive external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of adaptive radiotherapy group patients. CT repositioning will be performed after 15fractions of external radiotherapy, then new target volume will be contoured and new radiotherapy plan will be formulated with the assistance of artificial intelligence program. New radiotherapy plan will be performed from the 17th fraction external radiotherapy.

Radiation: Adaptive radiotherapy

Control group

ACTIVE COMPARATOR

Concurrent external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of control group patients.

Radiation: no adaptive radiotherapy

Interventions

Adaptive radiotherapy RADIATION

CT repositioning will be performed after 15fractions of external radiotherapy, then new target volume will be contoured and new radiotherapy plan will be formulated with the assistance of artificial intelligence program. New radiotherapy plan will be performed from the 17th fraction external radiotherapy.

Adaptive radiotherapy group

no adaptive radiotherapy RADIATION

Concurrent external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of control group patients

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• pathologically confirmed cervical squamous cell carcinoma or adenocarcinoma without treatment before;
• Age: ≥18 years old;
• The International Federation of Gynecology and Obstetrics(FIGO) stage: IB2 to IVA, or IVB with only para-aortic lymph node metastasis, refused or could not be treated by surgery;
• Eastern Cooperative Oncology Group(ECOG)score ≤2;
• good bone marrow, hematopoietic and liver and kidney function: absolute neutrophil count (ANC) ≥ 1.5 ☓ 109 / L, the platelet count ≥100 ☓ 109 / L, or hemoglobin \> 90 g/L, serum bilirubin \< 1.5 ☓ upper limit of normal reference value(ULN), aspartate aminotransferase(AST) and alanine aminotransferase(ALT)\< 2.5 ☓ ULN, serum creatinine clearance ≥ 50 ml/min.
• provide informed consent.

You may not qualify if:

• women in pregnancy or nursing;
• contraindications to chemoradiotherapy;
• subjects participating in other clinical trials or participating in other clinical trials within 30 days;

Sponsors & Collaborators

• The University of Hong Kong-Shenzhen Hospital: lead

Study Sites (1)

HongKong University Shenzhen Hospital

Shenzhen, Guangdong, 518053, China

RECRUITING

Related Publications (24)

• Arbyn M, Castellsague X, de Sanjose S, Bruni L, Saraiya M, Bray F, Ferlay J. Worldwide burden of cervical cancer in 2008. Ann Oncol. 2011 Dec;22(12):2675-2686. doi: 10.1093/annonc/mdr015. Epub 2011 Apr 6.

  PMID: 21471563 BACKGROUND

• Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.

  PMID: 26808342 BACKGROUND

• Kjaer SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst. 2010 Oct 6;102(19):1478-88. doi: 10.1093/jnci/djq356. Epub 2010 Sep 14.

  PMID: 20841605 BACKGROUND

• Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108. doi: 10.3322/canjclin.55.2.74.

  PMID: 15761078 BACKGROUND

• International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007 Feb 15;120(4):885-91. doi: 10.1002/ijc.22357.

  PMID: 17131323 BACKGROUND

• Dugue PA, Rebolj M, Garred P, Lynge E. Immunosuppression and risk of cervical cancer. Expert Rev Anticancer Ther. 2013 Jan;13(1):29-42. doi: 10.1586/era.12.159.

  PMID: 23259425 BACKGROUND

• Barnholtz-Sloan J, Patel N, Rollison D, Kortepeter K, MacKinnon J, Giuliano A. Incidence trends of invasive cervical cancer in the United States by combined race and ethnicity. Cancer Causes Control. 2009 Sep;20(7):1129-38. doi: 10.1007/s10552-009-9317-z. Epub 2009 Mar 1.

  PMID: 19253025 BACKGROUND

• Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. doi: 10.1056/NEJM199904153401502.

  PMID: 10202165 BACKGROUND

• Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.

  PMID: 19001332 BACKGROUND

• Klopp AH, Moughan J, Portelance L, Miller BE, Salehpour MR, Hildebrandt E, Nuanjing J, D'Souza D, Souhami L, Small W Jr, Gaur R, Jhingran A. Hematologic toxicity in RTOG 0418: a phase 2 study of postoperative IMRT for gynecologic cancer. Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):83-90. doi: 10.1016/j.ijrobp.2013.01.017.

  PMID: 23582248 BACKGROUND

• Tyagi N, Lewis JH, Yashar CM, Vo D, Jiang SB, Mundt AJ, Mell LK. Daily online cone beam computed tomography to assess interfractional motion in patients with intact cervical cancer. Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):273-80. doi: 10.1016/j.ijrobp.2010.06.003. Epub 2010 Nov 23.

  PMID: 21109360 BACKGROUND

• Pathy S, Kumar L, Pandey RM, Upadhyay A, Roy S, Dadhwal V, Madan R, Chander S. Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma. Asian Pac J Cancer Prev. 2015;16(12):5075-9. doi: 10.7314/apjcp.2015.16.12.5075.

  PMID: 26163644 BACKGROUND

• Perez CA, Grigsby PW, Castro-Vita H, Lockett MA. Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 1995 Jul 30;32(5):1275-88. doi: 10.1016/0360-3016(95)00220-S.

  PMID: 7635767 BACKGROUND

• Petereit DG, Sarkaria JN, Chappell R, Fowler JF, Hartmann TJ, Kinsella TJ, Stitt JA, Thomadsen BR, Buchler DA. The adverse effect of treatment prolongation in cervical carcinoma. Int J Radiat Oncol Biol Phys. 1995 Jul 30;32(5):1301-7. doi: 10.1016/0360-3016(94)00635-X.

  PMID: 7635769 BACKGROUND

• Holschneider CH, Petereit DG, Chu C, Hsu IC, Ioffe YJ, Klopp AH, Pothuri B, Chen LM, Yashar C. Brachytherapy: A critical component of primary radiation therapy for cervical cancer: From the Society of Gynecologic Oncology (SGO) and the American Brachytherapy Society (ABS). Brachytherapy. 2019 Mar-Apr;18(2):123-132. doi: 10.1016/j.brachy.2018.11.009. Epub 2019 Jan 18.

  PMID: 30665713 BACKGROUND

• Tsien C, Cao Y, Chenevert T. Clinical applications for diffusion magnetic resonance imaging in radiotherapy. Semin Radiat Oncol. 2014 Jul;24(3):218-26. doi: 10.1016/j.semradonc.2014.02.004.

  PMID: 24931097 BACKGROUND

• Ohkubo Y, Ohno T, Noda SE, Kubo N, Nakagawa A, Kawahara M, Abe T, Kiyohara H, Wakatsuki M, Nakano T. Interfractional change of high-risk CTV D90 during image-guided brachytherapy for uterine cervical cancer. J Radiat Res. 2013 Nov 1;54(6):1138-45. doi: 10.1093/jrr/rrt073. Epub 2013 Jun 3.

  PMID: 23732770 BACKGROUND

• Fu ZZ, Peng Y, Cao LY, Chen YS, Li K, Fu BH. Value of apparent diffusion coefficient (ADC) in assessing radiotherapy and chemotherapy success in cervical cancer. Magn Reson Imaging. 2015 Jun;33(5):516-24. doi: 10.1016/j.mri.2015.02.002. Epub 2015 Feb 7.

  PMID: 25660642 BACKGROUND

• Onal C, Yildirim BA, Guler OC, Mertsoylu H. The Utility of Pretreatment and Posttreatment Lymphopenia in Cervical Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy. Int J Gynecol Cancer. 2018 Oct;28(8):1553-1559. doi: 10.1097/IGC.0000000000001345.

  PMID: 30247248 BACKGROUND

• Joo J, Shin HJ, Park B, Park SY, Yoo CW, Yoon KA, Kong SY, Kim YJ, Kim SS, Kim JY. Integration Pattern of Human Papillomavirus Is a Strong Prognostic Factor for Disease-Free Survival After Radiation Therapy in Cervical Cancer Patients. Int J Radiat Oncol Biol Phys. 2017 Jul 1;98(3):654-661. doi: 10.1016/j.ijrobp.2017.02.226. Epub 2017 Apr 13.

  PMID: 28581408 BACKGROUND

• Harry VN, Semple SI, Gilbert FJ, Parkin DE. Diffusion-weighted magnetic resonance imaging in the early detection of response to chemoradiation in cervical cancer. Gynecol Oncol. 2008 Nov;111(2):213-20. doi: 10.1016/j.ygyno.2008.07.048. Epub 2008 Sep 6.

  PMID: 18774597 BACKGROUND

• Escande A, Haie-Meder C, Maroun P, Gouy S, Mazeron R, Leroy T, Bentivegna E, Morice P, Deutsch E, Chargari C. Neutrophilia in locally advanced cervical cancer: A novel biomarker for image-guided adaptive brachytherapy? Oncotarget. 2016 Nov 15;7(46):74886-74894. doi: 10.18632/oncotarget.12440.

  PMID: 27713124 BACKGROUND

• Reuze S, Orlhac F, Chargari C, Nioche C, Limkin E, Riet F, Escande A, Haie-Meder C, Dercle L, Gouy S, Buvat I, Deutsch E, Robert C. Prediction of cervical cancer recurrence using textural features extracted from 18F-FDG PET images acquired with different scanners. Oncotarget. 2017 Jun 27;8(26):43169-43179. doi: 10.18632/oncotarget.17856.

  PMID: 28574816 BACKGROUND

• Schernberg A, Bockel S, Annede P, Fumagalli I, Escande A, Mignot F, Kissel M, Morice P, Bentivegna E, Gouy S, Deutsch E, Haie-Meder C, Chargari C. Tumor Shrinkage During Chemoradiation in Locally Advanced Cervical Cancer Patients: Prognostic Significance, and Impact for Image-Guided Adaptive Brachytherapy. Int J Radiat Oncol Biol Phys. 2018 Oct 1;102(2):362-372. doi: 10.1016/j.ijrobp.2018.06.014. Epub 2018 Jun 18.

  PMID: 29920324 BACKGROUND

Related Links

• National Comprehensive Cancer Network(NCCN)

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Radiation Injuries

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Wounds and Injuries

Study Officials

• Zhi-Yuan Xu, master

  HongKong University Shenzhen Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhi-Yuan Xu, master

CONTACT

+86 18307555170; xuzy@hku-szh.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Total 122 cases of IB2-IVA cervical cancer will be randomly enrolled. Concurrent external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of control group patients. Concurrent adaptive external volumetric rotational intensity modulated radiotherapy and chemotherapy followed by image-guided adaptive brachytherapy is the treatment strategies of experimental group patients. CT repositioning will be performed after 15fractions of external radiotherapy, then new target volume will be contoured and new radiotherapy plan will be formulated with the assistance of artificial intelligence program. New radiotherapy plan will be performed from the 17th fraction external radiotherapy.

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 16, 2019
• Study Start: December 18, 2019
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: March 27, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)