Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Using Infusional Gemcitabine: Immune Cell...

Area of Science:

• Oncology
• Immunotherapy
• Rectal Cancer Research

Background:

• Standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) uses capecitabine or 5-fluorouracil.
• Gemcitabine, a radiosensitizer, possesses immunomodulatory properties.
• The impact of preoperative gemcitabine with radiotherapy on LARC microenvironment and long-term survival requires further elucidation.

Purpose of the Study:

• To evaluate the efficacy and immunomodulatory effects of neoadjuvant concurrent gemcitabine and radiotherapy in LARC.
• To assess long-term survival outcomes, pathological complete response (pCR), and immune cell infiltration.
• To compare outcomes with historical controls receiving capecitabine-based chemoradiation.

Main Methods:

• Phase II clinical trial update involving 40 patients with LARC.
• Treatment: neoadjuvant chemoradiotherapy (external beam radiation with weekly infusional gemcitabine) followed by surgery and adjuvant capecitabine.
• Secondary analysis included immunohistochemistry for immune cell infiltration (pre- and post-treatment) and comparison with historical controls.

Main Results:

• Updated median progression-free survival (PFS) of 70 months; estimated 5-year PFS and overall survival (OS) were 54.4% and 67.5%, respectively.
• Gemcitabine significantly increased total immune cell infiltration (p=0.026), CD8+ T cell density (p=0.001), and PD-L1+ immune cells (p=0.032) in resected tumors.
• Toxicities and pCR rates were comparable to established regimens.

Conclusions:

• Neoadjuvant infusional gemcitabine chemoradiotherapy provides durable survival and significant immune cell enrichment in LARC.
• The observed immunomodulatory effects, including increased CD8+ T cells and PD-L1+ cells, suggest potential for enhanced systemic disease control.
• Further research combining gemcitabine with immunotherapy is warranted to improve outcomes in LARC.