Phase I De-escalated RT in Endometrial Cancer

Area of Science:

• Gynecologic Oncology
• Radiation Oncology
• Medical Oncology

Background:

• The safety and efficacy of hypofractionated-radiation (hypo-RT) combined with chemotherapy for locally advanced endometrial cancer remain largely unknown.
• This study aimed to evaluate the safety of hypo-RT when sequenced after chemotherapy in this patient population.

Purpose of the Study:

• To assess the safety and tolerability of a treatment regimen involving adjuvant chemotherapy followed by hypofractionated radiation therapy (hypo-RT) for locally advanced endometrial cancer.
• To determine the rates of acute and late high-grade toxicities (G3-5) in gastrointestinal, genitourinary, and hematologic systems.

Main Methods:

• A phase I trial enrolled patients with FIGO 2009 stage III-IVA endometrioid adenocarcinoma or any stage serous, clear cell, or carcinosarcoma.
• Patients underwent surgical staging, adjuvant chemotherapy, and intensity-modulated radiation therapy (25 Gy/5 fractions) to the vaginal cuff and pelvis.
• Primary endpoints included acute and late high-grade toxicities; secondary endpoints included quality of life and survival outcomes.

Main Results:

• Twenty-five patients were enrolled and evaluable. Most completed chemotherapy (21/25) and all completed hypo-RT (25/25).
• Acute high-grade toxicities were 0% for GI and GU, and 12% for hematologic. Late high-grade toxicities were 0% for GI and GU, and 4% for hematologic.
• No G4-5 toxicities were observed. At a median follow-up of 24.7 months, recurrence rates were 4% in-field and 16% distant; cancer-related deaths were 8%.

Conclusions:

• Hysterectomy followed by adjuvant chemotherapy and hypo-RT is a safe treatment strategy for locally advanced endometrial cancer.
• The regimen demonstrated a low incidence of high-grade toxicities, indicating good tolerability.
• This combined modality approach warrants further investigation in a randomized clinical trial to confirm efficacy.