Translating spared and delayed tumor-draining lymph node irradiation into clinical practice: Current clinical trials and future directions.

Sparing lymph node irradiation is emerging as a promising strategy to leverage the synergy between radiotherapy and immunotherapy for definitive cancer treatment. Recent preclinical research highlighted the pivotal role of the communication between the primary irradiated tumor and tumor-draining lymph nodes (DLNs) and demonstrated immunological advantages of delaying DLN irradiation compared to traditional concurrent approaches. By temporally separating tumor irradiation from lymph node irradiation, this strategy preserves a potent anti-tumor immune response while maintaining effective control of the primary irradiated tumor and tumor-positive lymph nodes. These findings have sparked a surge of clinical interest with inspiring studies designed to implement sparing and delaying DLN irradiation into clinical practice. The present work provides an overview of ongoing clinical trials categorized by tumor localization.