Application of FLIC model to predict adverse events onset in neuroendocrine tumors treated with PRRT

Abstract

To develop predictive models of side effect occurrence in GEPNET treated with PRRT. Metastatic GEPNETs patients treated in our centre with PRRT (177Lu-Oxodotreotide) from 2019 to 2020 were considered. Haematological, liver and renal toxicities were collected and graded according to CTCAE v5. Patients were grouped according with ECOG-PS, number of metastatic sites, previous treatment lines and therapies received before PRRT. A FLIC model with backward selection was used to detect the most relevant predictors. A subsampling approach was implemented to assess variable selection stability and model performance. Sixty-seven patients (31 males, 36 females, mean age 63) treated with PRRT were considered and followed up for 30 weeks from the beginning of the therapy. They were treated with PRRT as third or further lines in 34.3% of cases. All the patients showed at least one G1–G2, meanwhile G3–G5 were rare events. No renal G3–G4 were reported. Line of PRRT administration, age, gender and ECOG-PS were the main predictors of haematological, liver and renal CTCAE. The model performance, expressed by AUC, was > 65% for anaemia, creatinine and eGFR. The application of FLIC model can be useful to improve GEPNET decision-making, allowing clinicians to identify the better therapeutic sequence to avoid PRRT-related adverse events, on the basis of patient characteristics and previous treatment lines.

Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms

“…Interesting study was made by Scalorbi et. all, where authors tried to find predictive factors of myelo-, nephro-, and hepatotoxicity by using a Firth’s logistic regression with intercept correction (FLIC) model [ 14 ]. On the cohort of 87 patients treated with 177 Lu-Oxodotreotide, (7.4 GBq iv per administration, with 8 ± 2 weeks interval) the subgroup of 67 patients—36 females and 31 males, with mean age of 63 was retrospectively analyzed.…”

“…These results may arise from different type of chemotherapy, which was used in both trials. Scalorbi et al, also noted there is an association between splenectomy and the risk of hematological complications, which can suggest that spleen removal can be a protective factor of this type of toxicity [ 14 ]. The limitation of that study is relatively short time of observation, which was 30 weeks from the beginning of the therapy.…”

An Overview of Regression Models for Adverse Events Analysis

“…As the event probabilities may be underestimated in those setting [ 24 ], it can be combined with useful type of penalization (e.g., Firth’s correction) to reduce biases [ 25 ]. Variants of Firth’s corrections have also been developed to improve the estimates of ORs [ 26 ]; they may be particularly useful for analyses of rare but serious AEs [ 27 , 28 ] with case-control designs [ 22 ]. Case-control designs The ORs directly stemming from the logistic regression are known to be interesting for risk evaluation in the case-control study designs, in which the baseline probability is not available.…”

“…As the event probabilities may be underestimated in those setting [ 24 ], it can be combined with useful type of penalization (e.g., Firth’s correction) to reduce biases [ 25 ]. Variants of Firth’s corrections have also been developed to improve the estimates of ORs [ 26 ]; they may be particularly useful for analyses of rare but serious AEs [ 27 , 28 ] with case-control designs [ 22 ].…”