3025 - The Addition of Pembrolizumab to Neoadjuvant Chemoradiotherapy and the Risk of Developing Postoperative Anastomotic Leakage for ESCC: An Analysis from a Prospective Cohort

S. Li, W. Qi, H. Li, J. Chen, and S. Zhao; Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Purpose/Objective(s): Currently, the standardized treatment option for locally advanced esophageal squamous cell cancer (ESCC) is neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy. Multiple studies have been performed to investigate the efficacy of combination of NCRT with immune checkpoint inhibitors for ESCC patients. However, concerns have raised regarding potentially increased risk of postoperative anastomotic leakage (AL) after NCRT. In the present study, we aim to compared to the difference of postoperative AL rate between NCRT with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced ESCC. Materials/

Methods: The gastric fundus (GF) was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established.
Results: A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p<0.05). Multivariate logistic regression analysis indicated that tumor length (p=0.012), volume of GF (p=0.003) and mean dose of GF (p=0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy.
Conclusion: Based on our prospective database, no significantly difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period. Abstract 3025 – Table 1:Baseline characteristics of included patients

Characteristics		Characteristics
Age (years)		Smoking status
=65	79 (49.4%)	Yes	103 (64.4%)
>65	81 (50.6%)	No	57 (35.6%)
cT stage		Drinking history
T2	18 (11.3%)	Yes	98 (61.3%)
T3	135 (84.4%)	No	62 (38.7%)
T4	7 (4.4%)	Co-morbidity
cN stage		Yes	67 (41.9%)
N0	7 (4.4%)	No	93 (58.1%)
N1	61 (38.1%)	Tumor location
N2 22	75 (46.9%)	Upper third	21 (13.1%)
N3 33	17 (10.6%)	Middle third	50 (31.3%)
Stage		Lower third	85 (53.1%)
II	7 (4.4%)	GEJ	4 (2.5%)
IIIA	9 (5.6%)	Location of anastomosis
IIIB	123 (76.9%)	Cervical anastomosis	56(49.6%)
IVA	21 (13.1%)	Intrathoracic anastomosis	68 (42.5%)
BMI	21.97 (16.43-30.89)	Concurrent chemotherapy regimen
Volume of Gastric fundus	15.47 (4.8-41.4cm3)	Pembrolizumab+paclitaxel+carboplatin	107 (67.9%)
Sex		paclitaxel+carboplatin	22 (13.8%)
Male	133 (83.1%)	Cisplatin+S-1/5-fluorouracil	31 (19.3%)
Female	27 (16.9%)	RT modality
Tumor length	4cm (1-15 cm)	IMRT	6 (47.5%)
		VMRT	84 (52.5%)