Clinical trial NCT04022018: Study on Adaptive Radiotherapy and Multimodal Information of Cervical Cancer Assisted by Artificial Intelligence
Official title: Study on Adaptive Radiotherapy and Multimodal Information of Cervical Cancer Assisted by Artificial Intelligence
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cervical Cancer
Radiotherapy Side Effect
Biomarker
Artificial Intelligence
Keywords: cervical cancer
adaptive radiotherapy
side effects
Lead sponsor: The University of Hong Kong-Shenzhen Hospital
Sponsor class: OTHER
First posted: 2019-07-16
Enrollment: 122
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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).

Detailed description: 1. Introduction and background 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.
2. Hypothesis and purpose Main endpoint: adaptive radiotherapy can reduce level 3 side effects or not. Secondary endpoint: 1. The differences of 2-year progression-free survival and overall survival between two groups. 2. To analyze Physical dosimetry differences between two groups, and the correlation between physical dosimetry differences and prognosis also will be evaluated. 3. To analyze the prediction and prognostic factors of adaptive radiotherapy for cervical cancer, and to provide supporting data for the subsequent optimization of cervical cancer treatment. 4. To evaluate the effectiveness of AI and conduct cost-benefit analysis.
3. Trial methodology and design 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.

   Meanwhile, concurrent chemotherapy regimen is cisplatin 40mg/m2/week (the maximum weekly dose should less than or equal to 70mg and no more than 6cycles). 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, PET/CT, MRI and other multimodal information. Fifth is cost-benefit analysis of AI.
4. Anticipated result and potential impact Adaptive radiotherapy can reduce side effects and obtain prognosis and prognostic factors of adaptive radiotherapy.

Eligibility criteria: Inclusion Criteria:

1. pathologically confirmed cervical squamous cell carcinoma or adenocarcinoma without treatment before;
2. Age: ≥18 years old;
3. 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;
4. Eastern Cooperative Oncology Group(ECOG)score ≤2;
5. 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.
6. provide informed consent.

Exclusion Criteria:

1. women in pregnancy or nursing;
2. contraindications to chemoradiotherapy;
3. subjects participating in other clinical trials or participating in other clinical trials within 30 days;

Primary outcomes:
measure: the difference in grade 3 side effects between the two groups
timeFrame: 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:
measure: 2-year PFS differences between the two groups
timeFrame: 2-year PFS
measure: 2-year OS differences between the two groups
timeFrame: 2-year OS
measure: the correlation between physical dosimetry differences and prognosis
timeFrame: correlation between physical dosimetry differences and 2year PFS
measure: the predictive factors for the response rate of concurrent chemoradiotherapy for cervical cancer
timeFrame: 3 months after radiotherapy
measure: the prognostic factors for the 2-year overall survival rate of patients with cervical cancer after concurrent chemoradiotherapy
timeFrame: 2 years after radiotherapy
measure: the time difference between labor and an artificial intelligence to design radiotherapy plans
timeFrame: 2years
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: HongKong University Shenzhen Hospital
state: Guangdong
Study officials:
affiliation: HongKong University Shenzhen Hospital
name: Zhi-Yuan Xu, master
role: PRINCIPAL_INVESTIGATOR
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