Background/Objectives: The aim of the study was to evaluate interobserver variability in the determination of the primary tumor for radiotherapy treatment planning in esophageal squamous cell carcinoma (ESCC). Methods: Sixteen patients with locally advanced ESCC were included in the analysis. In all patients positron emission tomography with computed tomography (PETC/CT) and magnetic resonance (MR) scans for radiotherapy planning were performed. Five experienced radiation oncologists delineated the primary tumor based on CT alone, MR alone, PET/CT, CT with fused MR and PET/CT with fused MR. Mean tumor volumes were calculated for each patient and imaging modality. The generalized conformity index (CIgen) was calculated to assess agreement in tumor determination. Results: The mean tumor volumes and CIgen for CT alone, MR alone, PET/CT, CT with fused MR and PET/CT with fused MR were 33.1 cm³, 30.2 cm³, 38.1 cm³, 31.9 cm³, 36.2 cm³ and 0.59, 0.64, 0.66, 0.63, 0.71, respectively. CIgen was significantly higher using PET/CT with fused MR compared to CT (p < 0.001) and PET/CT (p = 0.002) and using PET/CT compared to CT (alone) (p = 0.003). Conclusions: Our study showed higher agreement in primary tumor determination in ESCC using PET/CT compared to CT alone. Higher agreement was also found using PET/CT with fused MR compared to CT alone and PET/CT.

Background/Objectives: Total neoadjuvant therapy (TNT), integrating systemic chemotherapy and radiotherapy before surgery or surveillance, has become a standard approach for locally advanced rectal cancer (LARC). However, optimal sequencing strategies and long-term outcomes of watch-and-wait (W&W) following sandwich TNT remain insufficiently characterized. We evaluated oncologic outcomes and treatment response in patients treated with an institutional sandwich TNT protocol. Methods: We conducted a retrospective cohort study of consecutive patients with LARC treated with sandwich TNT (induction chemotherapy followed by hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost [IMRT-SIB] chemoradiotherapy and consolidation chemotherapy) at the Institute of Oncology Ljubljana between 2016 and 2023. The primary endpoint was an overall complete response (CR; pathological [pCR] and clinical [cCR]). Secondary endpoints included tumor regression grade (TRG), major pathological response (MPR), R0 resection rate, organ preservation, overall survival (OS), and disease-free survival (DFS). Results: Among 205 patients (median age 61 years), overall CR was 29.5% (pCR 19.3% and cCR 10.2%). Major pathological response (TRG 3–4) occurred in 37.6%. R0 resection was achieved in 94.5%. In the W&W cohort (n = 21), local regrowth occurred in 33.3% (95% CI, 14.6–57.0%) over a median follow-up of 4.96 years. Total mesorectal excision (TME)-free survival at 5 years was 73.1% (95% CI, 55.0–97.2%). Estimated 5-year OS was 81.1% (95% CI, 75.5–87.2%) and 5-year DFS was 75.2% (95% CI, 69.0–82.0). In multivariable analysis, non-R0 resection (HR 6.06, 95% CI, 1.99–18.42), MRI circumferential resection margin positivity (HR 3.11, 95% CI, 1.53–6.33), and MRI extramural vascular invasion positivity (HR 1.97, 95% CI, 1.05–3.91) remained independent predictors of DFS. Conclusions: Institutional sandwich TNT yields meaningful tumor response and durable survival in MRI-defined high-risk LARC. Structured W&W offers organ preservation with acceptable oncologic control under intensive surveillance.

Background/Objectives: Total neoadjuvant therapy (TNT), integrating systemic chemotherapy and radiotherapy before surgery or surveillance, has become a standard approach for locally advanced rectal cancer (LARC). However, optimal sequencing strategies and long-term outcomes of watch-and-wait (W&W) following sandwich TNT remain insufficiently characterized. We evaluated oncologic outcomes and treatment response in patients treated with an institutional sandwich TNT protocol. Methods: We conducted a retrospective cohort study of consecutive patients with LARC treated with sandwich TNT (induction chemotherapy followed by hypofrac-tionated intensity-modulated radiotherapy with simultaneous integrated boost [IMRT-SIB] chemoradiotherapy and consolidation chemotherapy) at the Institute of Oncology Ljubljana between 2016 and 2023. The primary endpoint was an overall complete response (CR; pathological [pCR] and clinical [cCR]). Secondary endpoints included tumor regression grade (TRG), major pathological response (MPR), R0 resec-tion rate, organ preservation, overall survival (OS), and disease-free survival (DFS). Results: Among 205 patients (median age 61 years), overall CR was 29.5% (pCR 19.3% and cCR 10.2%). Major pathological response (TRG 3–4) occurred in 37.6%. R0 resec-tion was achieved in 94.5%. In the W&W cohort (n=21), local regrowth occurred in 33.3% (95% CI 14.6–57.0%) over a median follow-up of 4.96 years. Surgery-free sur-vival at 5 years was 73.1% (95% CI 55.0–97.2%). Estimated five-year OS was 81.1% (95% CI 75.5–87.2%) and 5-year DFS was 75.2% (95% CI 69.0–82.0%). In multivariable analysis, non-R0 resection (HR 6.06), MRI circumferential resection margin positivity (HR 3.11), and extramural vascular invasion positivity (HR 1.97) remained independ-ent predictors of DFS. Conclusions: Sandwich TNT yields meaningful tumor response and durable survival in MRI-defined high-risk LARC. Structured W&W offers organ preservation with acceptable oncologic control under intensive surveillance.