Investigating the Correlation Between Pre-Treatment Imaging-Derived Body Composition, Chemotherapy Dose Adjustment, and Treatment Efficacy in Gynecological Cancer Patients "

Endometrial cancer ranks sixth in incidence among women worldwide and is rising, while ovarian cancer, though less common, remains the leading cause of gynecologic cancer mortality. Standard adjuvant chemotherapy for these malignancies includes paclitaxel (dose based on body surface area, BSA) and carboplatin (dose based on AUC). However, BSA-based dosing does not account for variations in body composition, which can significantly influence drug distribution, toxicity, and treatment efficacy.

Retrospective analysis of 124 endometrial cancer patients at National Cheng Kung University Hospital demonstrated that CT-derived skeletal muscle parameters (SMA, SMI) are significantly associated with grade ≥3 hematologic toxicities and outperform traditional clinical judgment for risk prediction. Patients experiencing severe hematologic toxicity within the first two cycles are more likely to experience repeated toxicities in subsequent cycles.

This trial integrates prospective randomized controlled trial (RCT) and retrospective target trial emulation.

Prospective RCT: 294 patients will be stratified by cancer stage and randomized 1:1 to intervention vs. control groups. The intervention group will undergo AI-assisted risk stratification based on preoperative CT body composition analysis, with high-risk patients receiving a 15% paclitaxel dose reduction from cycle 1. The control group will receive standard-of-care dosing adjustments based on clinical judgment.

Retrospective analysis: Patients diagnosed from 2012-2024 with available CT images and complete treatment records will be analyzed using propensity score methods to control for confounders.

Primary endpoint: incidence of grade ≥3 leukopenia or neutropenia within the first two cycles.

Secondary endpoints: chemotherapy cycle delay (>7 days), hospitalization rate, HRQoL (CIPN, EORTC-QoL), two-year PFS and OS, cost-effectiveness (ICER, VBP).

The trial hypothesizes that AI-guided dosing adjustments will reduce severe hematologic toxicity rates from 75% to 60% without compromising relative dose intensity (>85%), thereby achieving both clinical and economic benefits.

Inclusion criteria

• Able to comprehend and willing to participate in this clinical trial, with signed informed consent.
• Underwent an abdominal computed tomography (CT) scan within three months prior to surgical treatment, with a non-contrast-enhanced single-slice image at the third lumbar vertebral level available for body composition analysis.
• Histologically or cytologically confirmed diagnosis of endometrial cancer or ovarian cancer.
• Age between 20 and 80 years.
• Good performance status (ECOG performance status of 0, 1, or 2).
• Adequate hematologic parameters:

• Hemoglobin ≥10 g/dL
• White blood cell count ≥3,000/μL
• Neutrophil count ≥1,500/μL
• Platelet count ≥100,000/μL
• Adequate organ function:

• Total bilirubin ≤1.5 times the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) / Aspartate aminotransferase (AST) ≤2.5 times ULN (≤5.0 times ULN for patients with liver metastases).
• Creatinine ≤ ULN. Exclusion Criteria

• Presence of other major diseases that may be exacerbated by chemotherapy (e.g., autoimmune diseases).

• History of other malignancies within the past two years before trial enrollment, except for adequately treated non-melanoma skin cancer, stage 0 cervical carcinoma, or ductal carcinoma in situ of the breast.

• Requirement for concurrent treatment of unrelated diseases during the trial period, including chemotherapy, radiotherapy, or investigational drugs.

• Mental status deemed unsuitable for participation in the clinical trial. 5. Expected survival time of less than six months. 6. Poor-quality abdominal CT images, clearly attributable to the following causes:

• Motion artifacts due to poor patient compliance.
• Noticeable scoliosis or kyphosis.
• Multiple lumbar vertebral compression fractures.
• Significant generalized edema.
• Presence of metallic implants in the lumbar spine or abdomen.
• Abdominal stoma or significant abdominal wall defects.
• Marked asymmetry or localized atrophy/deficiency of the core abdominal musculature.