Comparison of Thrombocytopenia and Splenomegaly in Locally Advanced Rectal Cancer Patients Receiving Total Neoadjuvant Therapy With and Without Immunotherapy
Shuwen Li, Mingxu Yan, Qiong Ma, Yiqun Sun, Zhen Zhang, Lijun Shen, Juefeng Wan, Hui Zhang, Ruiyan Wu, Fan Xia, Yaqi WangABSTRACT
Background
Thrombocytopenia is a common toxicity of oxaliplatin‐based chemotherapy and may be linked to hepatic sinusoidal obstruction and splenic enlargement. In the TORCH trial, adding PD‐1 blockade to an oxaliplatin‐containing total neoadjuvant therapy (TNT) regimen improved tumor response in patients with locally advanced rectal cancer (LARC), but thrombocytopenia appeared more frequent and more severe. Here, we evaluated whether adding PD‐1 blockade to TNT increased thrombocytopenia risk and explored its association with hepatic injury and splenomegaly.
Methods
We retrospectively reviewed 181 LARC patients treated at Fudan University Shanghai Cancer Center. The cohort included 44 patients who received long‐course chemoradiotherapy (LCRT) followed by oxaliplatin‐containing chemotherapy (Ox‐TNT), 41 who received LCRT followed by irinotecan‐based chemotherapy (Iri‐TNT), and 96 who received short‐course radiotherapy plus six cycles of CAPOX and toripalimab (iTNT). We collected serial blood test results and measured liver and spleen volumes before and after treatment. Thrombocytopenia was graded according to CTCAE v5.0.
Results
Among 181 patients, thrombocytopenia occurred in 118 (65.2%), and splenomegaly in 69 (38.1%). Both events were most frequent in iTNT group, with incidences of 83.3% and 61.5%, respectively. Rates were lower in Ox‐based TNT group (50.0% and 13.6%) and in Iri‐based TNT group (39.0% and 9.8%), respectively. Platelet count showed an inverse correlation with both increased AST level ( p < 0.001) and splenic volume ( p < 0.001). In multivariate analysis, iTNT ( p = 0.002), splenomegaly ( p = 0.003), and older age ( p = 0.004) were independently associated with G2‐4 thrombocytopenia. Factors that independently predicted splenomegaly included iTNT ( p < 0.001), direct bilirubin ( p = 0.031), hepatomegaly ( p = 0.032), and AST ( p = 0.032). In the iTNT group, splenomegaly ( p = 0.009) and older age ( p = 0.033) remained associated with G2‐4 thrombocytopenia. Lower CD8 + CD28 + T cells and higher NK cells were associated with thrombocytopenia.
Conclusions
PD‐1 blockade added to TNT was associated with more severe thrombocytopenia than conventional TNT in LARC patients, possibly through greater hepatic injury and splenomegaly.