Online Adaptive Radiotherapy Cervical Cancer With Reduced Margin for Cervical Cancer

NCT05880485Active, Not RecruitingPHASE1, PHASE2INTERVENTIONAL

Summary

Online adaptive radiotherapy (oART) has demonstrated to be feasible to reduce planning target volume (PTV) margins for cervical cancer. To explore the value of reduced margins in oART for cervical cancer, we conducted a prospective clinical trial to determine the clinical efficacy and toxicity of reduced margins.

Key Facts

Lead Sponsor

Peking Union Medical College Hospital

Enrollment

30

Start Date

2023-02-02

Completion Date

2023-11-06

Study Type

INTERVENTIONAL

Official Title

A Prospective Study to Evaluate Online Adaptive Radiotherapy in Cervical Cancer With Reduced Margin

Interventions

online adaptive radiotherapy

Conditions

Uterine Cervical Neoplasm

Eligibility

Age Range

18 Years – 75 Years

Sex

FEMALE

Inclusion Criteria:

1. Patients must be informed of the investigational nature of this study and give written informed consent before treatment.
2. Age ≥18 years and ≤ 75 years.
3. Patients with newly histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, et al.
4. No evidence of para-aortic metastatic lymph nodes (MLNs) and inguinal lymph nodes on CT, MRI or positron emission tomograph (PET)/CT.
5. No contraindications to CT scanning.
6. No evidence of distant metastasis (FIGO stage IVB).
7. Adequate marrow: neutrophile granulocyte count ≥1.5\*10\^9/L, hemoglobin ≥ 80 g/L, platelet count ≥100\*10\^9/L.
8. Normal liver and kidney function: Creatinine (Cr) \< 1.5 mg/dl, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) \< 2\*upper limit of normal (ULN).

Exclusion Criteria:

1. With common iliac MLNs.
2. Tumor extended to the lower third of the vagina.
3. Tumor spread to mucosa of the bladder or rectum.
4. Prior surgery (including pelvic or para-aortic lymph nodes resection, except for tumor biopsy), radiotherapy or chemotherapy to primary tumor or nodes.
5. Prior malignancy.
6. History of previous radiotherapy to the abdomen or pelvis.
7. Pregnancy or lactation.
8. Active inflammatory bowel disease, or history of severe stomach or duodenal ulcer.
9. Active infection with fever.
10. Patients with unacceptable risk that intracavitary brachytherapy can not be conducted.
11. Any severe disease which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control, and emotional disturbance.

Outcome Measures

Primary Outcomes

Patient-reported acute toxicity

Patient-reported acute toxicity evaluated with European Organization for Research and Treatment of Cancer Quality of Life C30 (EORTC QLQ-C30) 3.0 questionnaire

Time frame: From the start of treatment to 3 months after treatment

Physician-reported acute toxicity

Physician-reported acute toxicity evaluated with Common Terminology Criteria for Adverse Events (CTCAE) 5.0

Time frame: From the start of treatment to 3 months after treatment

Secondary Outcomes

Late toxicity evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme

Evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme

Time frame: 2-year

The irradiated doses of organs at risk

The organs at risk includes bladder, rectum, bone marrow, femur head left, femur head right and bowel that may be irradiated near the target volume

Time frame: Through study completion, an average of eight month

The dose coverage of target volume as assessed by planing tumor volume V100%

Planing tumor volume V100%, defined as the planing tumor volume receiving at least 100% of the prescribed dose (V100%), is used to evaluate the dose coverage of target volume.

Time frame: Through study completion, an average of eight month

Target volume contouring accuracy

For every target in each fraction, the evaluation of accuracy for target contouring are categorized as follow: no edits, minor edits, moderate edits, major edits and not applicable.

Time frame: Through study completion, an average of eight month

Response evaluation evaluated with RECIST 1.1

Evaluated with RECIST 1.1

Time frame: One month after treatment

Movement of the uterus during per radiotherapy fractions

The pre- and post-treatment CBCT scans will be obtained during per treatment. The uterus intra-fractional motion were evaluated by comparison of uterus centroid from pre-treatment CBCT and uterus centroid from post-treatment images.

Time frame: Through study completion, an average of eight month

Movement of the cervix during per radiotherapy fractions

The pre- and post-treatment CBCT scans will be obtained during per treatment. The cervix intra-fractional motion were evaluated by comparison of cervix centroid from pre-treatment CBCT and cervix centroid from post-treatment images.

Time frame: Through study completion, an average of eight month

Progression-free survival

Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever is first.

Time frame: 2-year

Personalized margin for cervical cancer

Pre- and post-treatment images are uploaded to the online adaptive radiotherapy simulator to re-delineate the target volume and determine the personalized margin range.

Time frame: Six month after treatment

Locations

Peking Union Medical College Hospital, Beijing, China

Linked Papers

2022-11-07

Spare the Bowel, Don't Spoil the Target: Optimal Margin Assessment for Online Cone Beam Adaptive Radiation Therapy (OnC-ART) of the Cervix

The standard treatment for locally advanced cervical cancer involves pelvic chemoradiation. Intensity modulated radiation therapy planning requires expansion of the cervix and uterus clinical target volume (CTV) by 1.5 to 2 cm to account for motion. With online cone beam adaptive radiation therapy (OnC-ART), interfractional movement is accounted for, which can potentially lead to smaller CTV to planned target volume (PTV) margins. In this study, we attempted to determine the optimal CTV-to-PTV margin for adequate coverage with OnC-ART and factors that can affect CTV coverage. A retrospective cohort of 21 patients with cervical cancer treated with definitive chemoradiation was included. Nine patients treated with nonadaptive radiation had the uterocervix contoured on pretreatment cone beam computed tomography (CBCT) and end-treatment CBCTs. Anterior-posterior, lateral, and superior-inferior shifts and the average shift in all directions were calculated. A CTV-to-PTV expansion was determined and verified on a validation cohort of 12 patients treated with OnC-ART. The average anterior-posterior, lateral, and superior-inferior shifts with standard deviation were 0.32 ± 1.55 cm, 0.12 ± 2.31 cm, and 1.67 ± 3.41 cm, respectively. A uniform 5-mm expansion around the pretreatment CTV covered 98.85% ± 1.23% of the end-treatment CTV. This 5-mm expansion was applied to our validation cohort treated with OnC-ART, and 98.39% ± 3.0% of the end-treatment CTV was covered. Time between CBCTs >30 minutes and change in bladder volume were significantly correlated to CTV coverage. Based on our analysis, a CTV-to-PTV margin of 5 mm is adequate to encompass 98% of the CTV. A significantly reduced margin could potentially decrease the toxicities associated with radiation for patients with cervical cancer and lead to improved patient reported toxicity outcomes. We recommend physicians begin with a 5-mm margin and assess adequate coverage with image guidance during daily adaptation.

Linked Investigators

Allen Yen

Kevin Albuquerque

Online Adaptive Radiotherapy Cervical Cancer With Reduced Margin for Cervical Cancer