Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests
Authors: Geel Jennifer A. , Hramyka Artsiom , du Plessis Jan , Goga Yasmin , Van Zyl Anel , Hendricks Marc G. , Naidoo Thanushree , Mathew Rema , Louw Lizette , Carr Amy , Neethling Beverley , Schickerling Tanya M. , Omar Fareed , Du Plessis Liezl , Madzhia Elelwani , Netshituni Vhutshilo , Eyal Katherine , Ngcana Thandeka V.Z. , Kelsey Tom , Ballott Daynia E. , Metzger Monika L. ,   for the South African Children's Cancer Study Group, Stones David , Cockroft Ruellyn , Davidson Alan , Andrade Anabela , Buchner Ane , Van Eyssen Ann , van Emmenes Barry , Rowe Biance , Stannard Clare , Stefan Cristina , Reynders David , MacKinnon Diane , Mathews Elmarie , Omar Fareed , Desai Farieda , Steytler Gesami , Naidu Gita , Poole Janet , Parkes Jeanette , Vermeulen Johani , Lecuona Karin , Thomas Karla , Bennett Kate , Reddy Kershinee , Moodley Keshnie , Pillay Komala , Kruger Mariana , van Heerden Jaques , Wainwright Linda , Schoonraad Leila , de Jager Lourens , Bassingthwaighte Mairi , Vaithilingum Manickavallie , Moonsamy Nicolene , Wedi Oloko , Radebe Palessa , Uys Ronelle , Poyiadjis Stelios , Ngcana Thandeka , Naidoo Thanushree , Thejpal Rajendra , Schwyzer Rosemarie , Du Plessis Johannes , Hendricks Candice , Hesseling Pieter , Vanemmenes Barry , Schoeman Judy , Adamjee Mohamed , Chitnis Milind , Hartley Pat , Mathiassen Wendy , Millar Alistair , Wright Colleen , Beringer Nadia , Mahlachana Ngoakoana , Nkabi Thandeka , Flood Jade , Jonas Mampoi , Van Staaden Hamidah , Naicker Thurandrie , Schubert Pawel , Masoka Bulelwa 
Published: October 2024

PURPOSE
Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers.

METHODS
Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers.

RESULTS
Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%.

CONCLUSION
Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.