MH-ART vs CF-IMRT in Postoperative Cervical/Endometrial Cancer (ARTISAN)

A Multicenter, Non-Inferiority, Phase III Randomized Controlled Trial Comparing Moderately Hypofractionated Online Adaptive Radiotherapy（MH-ART） vs. Conventional Fractionated Intensity-Modulated Radiotherapy（CF-IMRT） in Postoperative Cervical Cancer and Endometrial Cancer

This is an investigator-initiated, prospective, national multi-center, phase III, randomized, open-label, non-inferiority clinical study. The hypothesis is that using online adaptive radiotherapy technology for moderately fractionated radiotherapy in post-operative patients with cervical/endometrial cancer may reduce radiotherapy-related toxicity and improve quality of life while ensuring target coverage. The objective is to evaluate treatment-related toxicity and efficacy of moderately fractionated online adaptive radiotherapy compared to conventionally fractionated intensity-modulated radiotherapy in post-operative cervical and endometrial cancer patients, aiming to provide a more precise, convenient, and cost-effective treatment option for patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; Endometrial Cancer
• Intervention / Treatment: Radiation: Moderately fractionated radiotherapy using online adaptive radiotherapy technology; Radiation: Conventionally fractionated radiotherapy using image-guided intensity-modulated radiotherapy technology.

Detailed Description

Randomization:

Intervention Group: Moderately fractionated radiotherapy using online adaptive radiotherapy technology.

Control Group: Conventionally fractionated radiotherapy using image-guided intensity-modulated radiotherapy technology.

Stratification Factors for Randomization:Participating study center; Disease type (Cervical cancer / Endometrial cancer); Receipt of concurrent chemotherapy

Study Objectives:

Primary Endpoint: Acute adverse reactions/toxicity Secondary Endpoints: Late adverse reactions/toxicity, 3-year local control rate, 3-year distant metastasis rate, 3-year progression-free survival (PFS), 3-year overall survival (OS), 3-year disease-free survival (DFS), quality of life, cost-effectiveness analysis related to treatment.

Study Population:

Planned Sample Size: 228 participants

Inclusion Criteria:

1. Participants must be fully voluntary and have decision-making capacity, providing written informed consent within 30 days prior to enrollment.
2. Age ≥18 years and ≤75 years.
3. ECOG performance status of 0-1, and expected to tolerate lying supine for half an hour.
4. Have undergone radical surgery for cervical cancer (procedure: radical hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy) or surgery for endometrial cancer (procedure: total hysterectomy + bilateral salpingo-oophorectomy ± pelvic and/or para-aortic lymph node dissection/sampling or sentinel lymph node biopsy).
5. For participants with cervical cancer, the following criteria must be met:

(1)Pathologically diagnosed with cervical squamous cell carcinoma or adenocarcinoma.

(2)Must have at least one of the following high-risk factors; or have other risk factors requiring postoperative radiotherapy: High-risk factors: Pelvic lymph node metastasis, or positive surgical margin, or parametrial invasion.

Other risk factors: Middle or deep one-third stromal invasion, regardless of tumor size and LVSI status; Tumor size ≥4cm, regardless of depth of stromal invasion and LVSI status; Adenocarcinoma: Tumor size ≥2cm, or positive LVSI, regardless of depth of stromal invasion.

6.For participants with endometrial cancer, the following criteria must be met: Endometrioid adenocarcinoma: Grade 3 with superficial myometrial invasion, accompanied by substantial LVSI or age ≥70 years; Grade 2 with deep myometrial invasion, accompanied by substantial LVSI or age ≥60 years; Grade 3 with deep myometrial invasion; FIGO 2009 Stage II-IIIC1.

Non-endometrioid adenocarcinoma: FIGO 2009 Stage I-IIIC1 (serous carcinoma, clear cell carcinoma, mixed type).

7.Participants with high-risk factors may receive a vaginal brachytherapy boost following the completion of external beam radiotherapy.

8.Participants with high-risk cervical cancer must receive concurrent sensitizing chemotherapy for ≥4 cycles.

9.Participants must be eligible to receive sequential or sandwich adjuvant chemotherapy as planned.

Study Duration: September 2025 to September 2030 Participant Involvement Period: Follow-up for over 3 years after radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaorong Hou, Professor; Phone Number: +86 18612672203; Email: houxr@pumch.cn
• Study Contact Backup: Name: Zihan Yan; Phone Number: +86 17860628938; Email: yanzihan_zora@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
      • Contact: Xiaorong Hou, Professor; Phone Number: +86 18612672203; Email: houxr@pumch.cn
      • Contact: Zihan Yan; Phone Number: +86 17860628938; Email: yanzihan_zora@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be fully voluntary and have decision-making capacity, providing written informed consent within 30 days prior to enrollment.
2. Age ≥18 years and ≤75 years.
3. ECOG performance status of 0-1, and expected to tolerate lying supine for half an hour.
4. Have undergone radical surgery for cervical cancer (procedure: radical hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy) or surgery for endometrial cancer (procedure: total hysterectomy + bilateral salpingo-oophorectomy ± pelvic and/or para-aortic lymph node dissection/sampling or sentinel lymph node biopsy).
5. For participants with cervical cancer, the following criteria must be met:

(1)Pathologically diagnosed with cervical squamous cell carcinoma or adenocarcinoma.

(2)Must have at least one of the following high-risk factors; or have other risk factors requiring postoperative radiotherapy: High-risk factors: Pelvic lymph node metastasis, or positive surgical margin, or parametrial invasion.

Other risk factors: Middle or deep one-third stromal invasion, regardless of tumor size and LVSI status; Tumor size ≥4cm, regardless of depth of stromal invasion and LVSI status; Adenocarcinoma: Tumor size ≥2cm, or positive LVSI, regardless of depth of stromal invasion.

6.For participants with endometrial cancer, the following criteria must be met: Endometrioid adenocarcinoma: Grade 3 with superficial myometrial invasion, accompanied by substantial LVSI or age ≥70 years; Grade 2 with deep myometrial invasion, accompanied by substantial LVSI or age ≥60 years; Grade 3 with deep myometrial invasion; FIGO 2009 Stage II-IIIC1.

Non-endometrioid adenocarcinoma: FIGO 2009 Stage I-IIIC1 (serous carcinoma, clear cell carcinoma, mixed type).

7.Participants with high-risk factors may receive a vaginal brachytherapy boost following the completion of external beam radiotherapy.

8.Participants with high-risk cervical cancer must receive concurrent sensitizing chemotherapy for ≥4 cycles.

9.Participants must be eligible to receive sequential or sandwich adjuvant chemotherapy as planned.

Exclusion Criteria:

1. Presence of confirmed distant metastasis or para-aortic lymph node metastasis;
2. Requirement for extended-field radiotherapy encompassing the para-aortic region;
3. Initiation of radiotherapy exceeds the specified time limit after surgery: exceeding 6 months post-surgery if adjuvant chemotherapy was administered, or exceeding 3 months post-surgery if no adjuvant chemotherapy was administered;
4. History of previous abdominal or pelvic radiotherapy;
5. History of or concurrent secondary primary malignancy (except for non-melanoma skin cancer, papillary/follicular thyroid carcinoma, or carcinoma in situ of the breast);
6. History of underlying intestinal diseases such as ulcerative colitis or Crohn's disease;
7. Cervical cancer with pathological types such as adenosquamous carcinoma, small cell carcinoma, clear cell carcinoma, or other special types; Endometrial cancer with pathological types such as undifferentiated carcinoma, carcinosarcoma, or other special types;
8. Pregnant or lactating women;
9. Presence of active infection or fever;
10. Other severe comorbidities that may significantly compromise protocol compliance, such as uncontrolled cardiac disease requiring treatment, renal disease, chronic hepatitis, poorly controlled diabetes, psychiatric disorders, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MH-ART; Moderately fractionated radiotherapy using online adaptive radiotherapy technology.	Radiation: Moderately fractionated radiotherapy using online adaptive radiotherapy technology; Treatment will be delivered using an online adaptive radiotherapy device. A moderately fractionated regimen will be employed, with a prescribed dose of 40.05 Gy in 15 fractions, administered once daily, five times per week.
Other: CF-IMRT; Conventionally fractionated radiotherapy using image-guided intensity-modulated radiotherapy technology.	Radiation: Conventionally fractionated radiotherapy using image-guided intensity-modulated radiotherapy technology.; Intensity-modulated radiotherapy techniques will be used, including FF-IMRT, VMAT, or TOMO. A conventionally fractionated regimen will be employed, with a prescribed dose of 45 Gy in 25 fractions, administered once daily, five times per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Toxicity	Toxicities occurring within 90 days (inclusive) from the start of radiotherapy are defined as acute toxicities. Acute toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Within 90 days (inclusive) from the start of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Late Toxicity	Toxicities occurring more than 90 days after the start of radiotherapy are defined as late toxicities. Late toxicities will be evaluated using the RTOG/EORTC Late Radiation Morbidity Scoring Scheme.	From 90 days after the start of radiotherapy until death from any cause, assessed up to 3 years.
3 years Local Recurrence Rate	The proportion of subjects who do not experience tumor recurrence or progression within the radiation field within 3 years after the end of radiotherapy.	From the end of radiotherapy until local recurrence or death from any cause, assessed up to 3 years.
3 years Distant Metastasis Rate	The proportion of subjects who develop distant metastasis within 3 years after the start of radiotherapy.	From the start of radiotherapy until distant metastasis or death from any cause, assessed up to 3 years.
3 years Progression-Free Survival	The time interval from the start of radiotherapy to the first occurrence of disease recurrence (local, regional, or distant) or death from any cause within 3 years after the start of radiotherapy.	From the start of radiotherapy until the first disease recurrence (local/regional/distant) or death from any cause, assessed up to 3 years.
3 years Overall Survival	The time interval from the start of radiotherapy to death from any cause within 3 years after the start of radiotherapy.	From the start of radiotherapy until death from any cause, assessed up to 3 years.
3 years Disease-Free Survival	The time interval from the start of radiotherapy to the first occurrence of local or regional recurrence, distant metastasis, or death from any cause within 3 years after the start of radiotherapy.	From the start of radiotherapy until the first local/regional recurrence, distant metastasis, or death from any cause, assessed up to 3 years.
Quality of Life	Quality of life will be assessed using the QLQ-C30 questionnaire, in combination with the disease-specific module (QLQ-CX24 for cervical cancer; QLQ-EN24 for endometrial cancer).	Baseline, at the end of radiotherapy, and every 3 months thereafter until 3 years from start of radiotherapy.
Treatment-Related Cost-Effectiveness Analysis	The cost assessment should cover both medical costs and non-medical costs.	From the start of radiotherapy until death from any cause, assessed up to 3 years.

Collaborators and Investigators

• Sponsor: Xiaorong Hou

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: September 24, 2025
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cervical cancer; Endometrial cancer; Moderately fractionated radiotherapy; Acute adverse reactions
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: ARTISAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No