Magnetic resonance-guided radiotherapy (MRgRT) represents a promising new image guidance technology for radiation treatment delivery combining an onboard MRI scanner with radiation delivery technology. By enabling real-time low-field or high-field MRI acquisition, it facilitates improved soft tissue delineation, adaptive treatment, and motion management. Now that MRgRT has been available for nearly a decade, research has shown the technology can be used to effectively shrink treatment margins to either decrease toxicity (in breast, prostate cancer, and pancreatic cancer) or facilitate dose-escalation and improved oncologic outcomes (in pancreatic and liver cancer), as well as enabling indications that require clear soft tissue delineation and gating (lung and cardiac ablation). In doing so, the use of MRgRT has the potential to significantly improve the outcomes and quality of life of the patients it treats. The present narrative review aims to describe the rationale for MRgRT, the current and forthcoming state of technology, existing studies, and future directions for the advancement of MRgRT, including associated challenges.

Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research shows that increased nodal involvement is a critical predictor of worse prognosis, raising questions about whether biological subtype or anatomic stage has a greater influence on outcomes in these discordant cases. We hypothesized that overall survival (OS) remains worse for LA-HR+/HER2- BC compared to ES-TNBC, despite both being classified as PPS IB. Methods: Using the National Cancer Database, we identified patients with LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2) and ES-TNBC (T1N0, grade 2–3) treated between 2004 and 2017. Patients without complete primary tumor stage, biomarker status, grade, TNM staging, or treated with neoadjuvant therapy were excluded. The primary endpoint was OS. Multivariable Cox regression evaluated OS between LA-HR+/HER2- BC and ES-TNBC. Results: Among 45,818 patients (17,359 LA-HR+/HER2- BC and 28,459 ES-TNBC), LA-HR+/HER2- BC had significantly worse 6-year OS (86.1% vs. 90.4%; HR = 1.63; p < 0.0001). Among patients receiving appropriate therapies, patients with LA-HR+/HER2- BC had 35% relatively higher risk of death (HR = 1.35; 1.24–1.48; p < 0.0001). These results highlight that LA-HR+/HER2- breast cancer has worse survival compared to ES-TNBC, despite both being classified as PPS IB and receiving all appropriate treatments. Conclusions: Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information.