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Objectives: To analyze the results of interstitial (IRT) high-dose-rate (HDR) brachytherapy (BT) in the primary treatment of patients with unresectable superior sulcus tumors (SST) combined with external beam radiotherapy (EBRT). Methods: Between 2013 and 2023, seven patients with unresectable SST were treated with combined BT and EBRT with or without concomitant chemotherapy. The patients' median age was 64 years (range, 49–79 years) and median tumor volume was 146.8 cm3 (range, 29.3–242.3 cm3). A median BT dose of 8 Gray (Gy) (range, 5–10 Gy) was prescribed and delivered in a single fraction. A median EBRT dose of 54 Gy (range, 30–59 Gy) was prescribed and administered normofractionated (single dose: 1.8 Gy). Results: We report the results of seven patients with SST treated with combined BT and EBRT and followed for a median of 38 months. The overall clinical response rate was 83.33% with five out of six patients achieving local control, while one out of six (16.66%) showed local and general progression. No deaths were attributed to the treatment itself; rather, one patient died during the course of therapy as a result of systemic progression. The most common radiation-related adverse events were grade I–II fatigue and mild paresthesia. No severe toxicity (CTCAE ≥ III°) was observed with interstitial high-dose-rate (HDR) BT combined with EBRT. Conclusions: For patients with unresectable superior sulcus tumors, interstitial HDR BT in combination with EBRT is a feasible treatment option that offers the potential for local control and long-term survival. The findings of this study should be validated in a larger patient cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: The NEORECT trial explored the use of circulating tumor DNA (ctDNA) dynamics as a biomarker to monitor treatment response in rectal cancer patients undergoing nCRT. Although ctDNA patterns showed some correlation with treatment outcomes, specificity was low, indicating limitations in using ctDNA alone to predict pathologic remission. The findings highlight the potential and challenges of ctDNA-based monitoring, suggesting that broader genetic analysis and larger studies are needed to enhance precision in non-surgical management approaches. Background/Objectives: Locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). As this approach achieves complete pathologic remissions (pCR) in approximately 30% of patients, it raises the question of whether surgery is always necessary. Non-surgical strategies, such as "watch and wait" (W&W), have shown similarly promising outcomes. However, there is an unmet need for reliable biomarkers predicting pCR. Analysis of circulating tumor DNA (ctDNA) has shown potential for monitoring treatment response and detecting minimal residual disease. We hypothesized that monitoring ctDNA changes during nCRT might facilitate the identification of individuals who achieve pCR. Methods: In the prospective single-center NEORECT trial, the plasma of forty rectal cancer patients was collected before, during, and after nCRT and before TME. Informative somatic mutations were identified in tissue biopsies by NGS and subsequently used for ctDNA quantification by dPCR. Results: The results identified three distinct ctDNA patterns: increase, decrease, and absence. Remarkably, undetectable DNA was observed in good responders, while a tenfold ctDNA increase was associated with the emergence of new metastases. Despite these insights, ctDNA alone demonstrated low specificity, with no significant correlation to pCR or long-term prognosis. A multimodal approach incorporating routinely available clinical parameters remains inadequate for accurately predicting pCR prior to TME. Conclusions: In conclusion, the NEORECT trial establishes the feasibility of ctDNA-based personalized monitoring for rectal cancer patients undergoing nCRT. However, the utility of ctDNA in enhancing pCR prediction for a W&W strategy warrants further investigation. Larger studies integrating multi-gene analyses and expanded clinical datasets are essential in the future. [ABSTRACT FROM AUTHOR]