Adaptive Radiotherapy in Patients With Gynecological Tumors (ProART)

Prospective Randomized Validation of Adaptive Radiotherapy in Patients With Gynecological Tumors and Indication for Radiotherapy

Prospective randomized evaluation of adaptive radiotherapy in the definitive radiotherapy of locally advanced gynecologic carcinoma (e.g. cervical carcinoma, endometrial carcinoma, vaginal carcinoma), in the postoperative situation or first series of external beam radiotherapy and in patients in whom radical surgery or HDR brachytherapy as dose boost is not an option.

Study Overview

• Status: Recruiting
• Conditions: Cervical Carcinoma; Radiation; Adaptive Radiotherapy; Image Guided Radiotherapy; Gynecological Tumor; Optimization; Curative Treatment; Adaptive Radiation Therapy
• Intervention / Treatment: Radiation: Adaptive Radiotherapy

Detailed Description

Online-adaptive radiotherapy (ART) makes it possible to adapt the dose distribution to the anatomical changes online immediately before each radiation fraction. Adaptive radiotherapy is a further development of image-guided radiotherapy (IGRT), which is now standard in radiotherapy. Here, a cone-beam CT (CBCT) is also performed at the beginning of each fraction, which is used to position the patients in relation to the radiation field arrangement of the initial radiation plan approved for the series. In contrast to ART, with IGRT the radiation plan cannot be adapted to deformations in the body from radiation fraction to radiation fraction, e.g. due to different rectum and bladder fillings.

In ART mode, the online adaptive treatment plan for the current treatment is then selected and approved by the specialist online onboard in all cases in which the current target volume for the tumor expansion is not sufficiently covered by the initial treatment plan pre-planned for the series with its planned tolerances, or surrounding normal tissue is exposed too much. If the ART plan does not show any clear dosimetric advantages over the reference plan, especially if the initial plan covers the target volume of the day well, there are no dose increases and the normal tissues are spared as intended, the initial radiation plan from the planning CT can also be used as in IGRT. The aim of this study is to treat at least 15 patients with locally advanced gynecological carcinoma (mainly cervical carcinoma, endometrial carcinoma, vaginal carcinoma), who are to receive definitive radiotherapy at the Department for Radiotherapy at the University Hospital Essen, in ART mode on the Ethos therapy device over an initial 10 radiation fractions. The dose distribution is always compared with the adaptive and the initial plan for the radiation series on the anatomy of the day by the specialist and medical physics expert. The aim of this study is to prospectively investigate what percentage of patients benefit from ART when using standard PTV margins and how to recognize the corresponding patients early in the series. Secondarily, it will be investigated in what proportion of patients the risk organ burden and the safety margins around the clinical target volume can be reduced with ART compared to IGRT and how large this reduction can be.

The EORTC and CTC AE toxicitiy scales and further assessment scales will be evaluated in order to quantify objective and subjective side effects.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Germany / NRW
    • Essen, Germany / NRW, Germany, 45147
      • Recruiting
      • Department for Radiotherapy, University Hospital Essen, National Center for Tumor Diseases (NCT) West
      • Contact: Maja Guberina, PD Dr. med. (MD), specialist; Phone Number: +492017232321; Email: maja.guberina@uk-essen.de
      • Contact: Ina Grübel
      • Principal Investigator: Maja Guberina, PD Dr. med. (MD)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

ECOG 0-1 confirmation by histophatology MR of the pelvis staging

Exclusion Criteria:

Recurrent disease Prior Radiotherapy in pelvic region stage pM1 or cM1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional Arm; Adaptive Radiotherapy	Radiation: Adaptive Radiotherapy; Adaptive Radiotherapy, online onboard adaptation of dose distribution with a specialist radiation oncologist and a medical physicist; Other Names: Adaptive Radiation Therapy
Active Comparator: Standard conventional Treatment Arm, IGRT	Radiation: Adaptive Radiotherapy; Adaptive Radiotherapy, online onboard adaptation of dose distribution with a specialist radiation oncologist and a medical physicist; Other Names: Adaptive Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rectal Toxicity	Rectum, EORTC CTC-AE (Common Toxicity Criteria (CTC) of the European Organisation for Research and Treatment of Cancer (EORTC)) 1-5, [score 1: nearly no toxicity, asymptomatic changes - score 5: worst outcome (death)]	2 weeks to 5 years
Bladder Toxicity	Bladder, EORTC CTC-AE (Common Toxicity Criteria (CTC) of the European Organisation for Research and Treatment of Cancer (EORTC)) 1-5, [score 1: nearly no toxicity, asymptomatic changes - score 5: worst outcome (death)]	2 weeks to 5 years
Skin Toxicity	Skin, EORTC CTC-AE (Common Toxicity Criteria (CTC) of the European Organisation for Research and Treatment of Cancer (EORTC)) 1-5, [score 1: nearly no toxicity, asymptomatic changes - score 5: worst outcome (death)]	2 weeks to 5 years
Lymph-Edema grade	Lymph-Edema, EORTC CTC-AE ( (Common Toxicity Criteria (CTC) of the European Organisation for Research and Treatment of Cancer (EORTC)) 1-3, [score 1: nearly no toxicity, asymptomatic changes - score 3: worst outcome, severe symptoms; limiting self care ADL]	2 weeks to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival	5 years
Overall Survival	Overall Survival	5 years

Collaborators and Investigators

• Sponsor: University Hospital, Essen

Publications and helpful links

General Publications

• Guberina M, Santiago Garcia A, Khouya A, Pottgen C, Holubyev K, Ringbaek TP, Lachmuth M, Alberti Y, Hoffmann C, Hlouschek J, Gauler T, Lubcke W, Indenkampen F, Stuschke M, Guberina N. Comparison of Online-Onboard Adaptive Intensity-Modulated Radiation Therapy or Volumetric-Modulated Arc Radiotherapy With Image-Guided Radiotherapy for Patients With Gynecologic Tumors in Dependence on Fractionation and the Planning Target Volume Margin. JAMA Netw Open. 2023 Mar 1;6(3):e234066. doi: 10.1001/jamanetworkopen.2023.4066.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: December 30, 2023
• First Submitted That Met QC Criteria: January 19, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: radiation; optimization; adaptive radiotherapy; Cervical carcinoma; curative treatment; adaptive radiation therapy; gynecological tumor; image guided radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma
• Other Study ID Numbers: 23-11675-BO

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: Yes
• product manufactured in and exported from the U.S.: Yes