Creation of High-Quality Robust Pancreas Plans for Daily Adaptive Hypofractionated Stereotactic Radiotherapy on the 0.35T MRI Linac

Abstract

Neoadjuvant chemoradiotherapy (NCRT) has been shown to increase survival in patients with locally advanced esophageal cancer (EC) compared to surgery alone. A single intensive protocol of NCRT (NP) was previously tested in phase I and II trials at our Center, resulting in encouraging results, thus becoming our standard in trimodality approach. Therefore, the aim of this analysis was to evaluate the efficacy and safety of this NP in the daily clinical practice and "real life" patients. Materials/Methods: Data of EC patients treated at our Center from January 2008 to December 2017 were prospectively collected. The NP schedule consists of an induction phase of weekly administered docetaxel, cisplatin, and 5-fluorouracil (TCF) for 3 weeks, followed by a concomitant phase of weekly TCF for 5 weeks concurrent with radiotherapy (50-50.4 Gy in 25-28 fractions). Primary endpoints were overall survival (OS), progression-free survival (PFS) and pathological complete response (pCR or ypT0N0). Secondary endpoint was toxicity. Results: 122 consecutive patients were included in the analysis, 55 (45.1%) squamous cell carcinoma (SCC) and 67 (54.9%) adenocarcinoma (ADC). The estimated median follow-up time was 62.1 months (95% CI 50-67.6 months). The median OS and PFS were 78.5 months (95% CI 42.3-not reached) and 39.5 months (95% CI 27.8-82.6), respectively. The 3-and 5-years OS rates were 64.2% (95% CI 54.7-72.2) and 54.8% (95% CI 44.7-63.9), and the corresponding PFS rates were 51.1% (95% CI 41.8-59.6) and 42.7% (95% CI 33.1-51.9), respectively. After NP, 107 (87.7%) patients underwent surgery, 105 of them (98.1%) achieved a radical resection (R0) and 55 (51.4%) a pCR, including 71.1% of SCC patients and 37.1% of ADC patients (p Z 0.001). Resected patients had a better OS than unresected patients (median: 97.4 vs 17. 8 months, HR 0.24, 95% CI 0.12-0.47, p<0.0001) and PFS (median: 46.2 vs 4.9 months, HR 0.28, 95% CI 0.15-0.52, p<0.0001). Patients with a pCR had a significantly lower risk of death (median OS: 117 vs 30.6 months, HR 0.3, 95% CI 0.16-0.56, p<0.0001) and disease relapse (median DFS: 117 vs 24.2 months, HR 0.35, 95% CI 0.2-0.61, p<0.0001). Of 119 (97.5%) patients who completed the NP, 32 (26.9%) experienced grade 3 acute hematological toxicity and 23 (19.3%) acute grade 3 non-hematological events. A potentially treatment-related death occurred in 4 (3.4%) patients. Tumor relapse occurred in 52 (42.6%) patients, with a systemic, loco-regional and mixed pattern of recurrence in 31 (59.6%), 7 (13.5%), and 14 (26.9%) patients, respectively. Conclusion: This retrospective study suggests that this intensive NP was able to achieve a high pCR rate and considerable long-term survival also in "real life" patients. Further research is necessary to evaluate whether surgery on demand is feasible in selected patients, such as complete responders with SCC.