Comparison of thrombocytopenia and splenomegaly in locally advanced rectal cancer patients receiving total neoadjuvant therapy with and without immunotherapy.

e15637 Background: Thrombocytopenia is one of the main adverse effects of oxaliplatin-based chemotherapy, probably due to the hepatic sinusoidal obstruction syndrome and splenomegaly. The integration of PD-1 inhibitors with oxaliplatin-based total neoadjuvant therapy (TNT) has achieved remarkable tumor regression but increased the incidence and severity of thrombocytopenia in patients with locally advanced rectal cancer (LARC) in our previous TORCH trial. Herein, we aimed to compare the thrombocytopenia in LARC patients receiving TNT with and without immunotherapy, and explore the correlation among liver injury, splenomegaly and thrombocytopenia. Methods: We conducted a retrospective study involving 181 LARC patients who received either Ox-based TNT (N = 44, long-course chemoradiotherapy [LCCRT] followed by oxaliplatin-based chemotherapy), Iri-based TNT (N = 41, LCCRT followed by irinotecan-based chemotherapy), or iTNT (N = 96, short-course radiotherapy and 6 cycles of CAPOX and PD-1 inhibitor from TORCH trial [NCT04518280]) at the Fudan University Shanghai Cancer Center. Blood laboratory tests were extracted before, during and after TNT/iTNT. Splenic and hepatic volumes were measured using automated techniques based on CT, MRI, or PET-CT at baseline and at the end of treatment. Thrombocytopenia was graded according to the CTCAE5.0 criteria. Splenomegaly was defined as an increase in spleen volume of more than 30% from baseline. Results: Among the 181 patients, 118 (65.2%) developed thrombocytopenia, and 69 (38.1%) developed splenomegaly. The iTNT group exhibited significantly higher rates of thrombocytopenia (89.6%) and splenomegaly (61.5%) compared to Ox-based TNT group(thrombocytopenia50.0%, splenomegaly13.6%) and Iri-based TNT group(thrombocytopenia61.0%, splenomegaly9.8%). Platelet count was negatively correlated with the increase in AST level (P < 0.001) and spleen volume (P < 0.001). In the multivariate analysis of the entire cohort, immunotherapy(P = 0.002), splenomegaly(P = 0.003) and older age(P = 0.004) were identified as independent predictive factors for G2-4 thrombocytopenia. Additionally, immunotherapy(P < 0.001), direct bilirubin(P = 0.031), hepatomegaly(P = 0.032) and AST(P = 0.032)were identified as independent predictive factors for splenomegaly. In patients receiving iTNT, splenomegaly (P = 0.009) and older age (P = 0.033) were still the major predictive factors for G2-4 thrombocytopenia. Conclusions: In LARC patients, the addition of PD-1 inhibitors to TNT lead to more severe thrombocytopenia compared to traditional TNT, probably due to increased liver injury and splenomegaly.