Background/Objectives: Recent advancements in the treatment of LACC have focused on improving outcomes through systemic treatment intensification. Therefore, this review aims to analyze the brachytherapy (BT) techniques employed in recent studies that are likely to change upcoming clinical guidelines, and to discuss the evolving role of IGABT in optimizing patient outcomes. Methods: This review focuses on BT practices reported across main phase III trials—OUTBACK, INTERLACE, CALLA, and KEYNOTE A18—compared with the EMBRACE I study. Analyzed parameters include BT modality, dose prescription techniques, imaging guidance, and overall treatment time (OTT). Results: In EMBRACE I, MRI-based IGABT was mandatory, with 43% of patients receiving an intracavitary/interstitial (IC/IS) applicator; cumulative EQD2 D90 HR-CTV was 90 Gy with a median OTT of 46 days. The OUTBACK trial relied predominantly on point A-based BT, with limited use of volume-based BT (28%). The INTERLACE trial reported mixed BT approaches: 70% point A-based, 30% volume-based, and 20% 2D BT. A median cervical dose of 79.4 Gy was reported. CALLA maintained strong protocol adherence, with 60% volume-based BT and a median tumor EQD2 dose of 83 Gy, although lower in the Japan cohort. In the KEYNOTE A 18 cohort, volume-based BT was performed in 88% of patients, with a median D90 HR-CTV dose of 87 Gy; IC/IS applicators were used in 23% of cases. Conclusions: Across these major studies, the following consistent pattern emerges: the quality and technique of BT impact survival outcomes and toxicity profile in LACC. MRI-based IGABT—with the use of IC/IS applicators when needed—is essential.

Vulvar cancer is a relatively rare neoplasm. The essential treatment is surgery for the primary tumour. However, postoperative recurrence rates are high, even in early-stage disease when tumour-free surgical margins are achieved or in the absence of associated risk factors (lymph node metastases, deep stromal invasion or invasion of the lymphatic vascular space). Radiotherapy plays an important role in the treatment of vulvar cancer. Adjuvant treatment after surgery as well as primary treatment of locally advanced vulvar cancer (LAVC) is composed of two key radiotherapy treatment scenarios, external beam radiation therapy (EBRT) either combined or not combined with brachytherapy (BT). In a recurrence setting, where surgery is not an option, BT alone or in combination with EBRT can be used. Compared to EBRT, BT has the radiobiological potential to improve dose to the target volume, minimise the dose to organs at risk, and facilitate hypofractionated-accelerated treatment. This narrative review presents recent data on the role of BT in the treatment of primary and/or recurrent vulvar cancer, including radiobiological, clinical, and therapeutic aspects.

Radiobiology has evolved from a mechanistic model based on DNA damage and response factors into a more complex model that includes effects on the immune system and the tumor microenvironment (TME). Irradiation has an immunomodulatory effect that can manifest as increased anti-tumor immunity or immunosuppression. Irradiation promotes an inflammatory microenvironment through the release of pro-inflammatory cytokines and endothelial damage, which recruit immune system cells to the irradiated area. Radiation-induced immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) and tumor antigens, triggers an anti-tumor immune response of both innate and adaptive immunity. Anti-tumor immunity can manifest at a distance from the irradiated area, a phenomenon known as the abscopal effect (AE), which involves dendritic cells and CD8+ T cells. Irradiation also produces an immunosuppressive effect mediated by tumor-associated macrophages (TAMs) and regulatory T lymphocytes (Tregs), which counterbalances the immunostimulatory effect. In this work, we review the mechanisms involved in the radiation-induced immune response, which support the combined treatment of RT and immunotherapy, focusing, where possible, on gynecologic cancer.