Radiomics and Machine Learning in Anal Squamous Cell Carcinoma: A New Step for Personalized Medicine?  
[PERSON]  
1 Radiation Oncology Department, Hopital Haut-Leveque, CHU Bordeaux, 33600 Pessac, France 12 Institut de Mathematiques de Bordeaux CNRS UMR 5251 & Universite de Bordeaux, MOnc Team, INRIA Bordeaux-Sud-Ouest, Talence, 33076 Bordeaux, France; [EMAIL_ADDRESS]  
[PERSON]  
3 Division of Radiation Oncology, Department of Oncology, McGill University, Montreal, QC H4A 3J1, Canada; [EMAIL_ADDRESS] (P.S.); [EMAIL_ADDRESS] (T.V.); [EMAIL_ADDRESS] (V.V.)  
3 [PERSON]  
3 Division of Radiation Oncology, Department of Oncology, McGill University, Montreal, QC H4A 3J1, Canada; [EMAIL_ADDRESS] (P.S.); [EMAIL_ADDRESS] (T.V.); [EMAIL_ADDRESS] (V.V.)  
3 [PERSON]  
3 Division of Radiation Oncology, Department of Oncology, McGill University, Montreal, QC H4A 3J1, Canada; [EMAIL_ADDRESS] (P.S.); [EMAIL_ADDRESS] (T.V.); [EMAIL_ADDRESS] (V.V.)  
3 [PERSON]  
3 Division of Radiation Oncology, Department of Oncology, McGill University, Montreal, QC H4A 3J1, Canada; [EMAIL_ADDRESS] (P.S.); [EMAIL_ADDRESS] (T.V.); [EMAIL_ADDRESS] (V.V.)  
3 [PERSON]  
disease has evolved from non-conservative surgery, namely abdomino-perineal resection (APR), to concomitant chemo-radiotherapy (CRT), based on the results of phase III trials performed in the 1990s [4,5]. This is because, apart from modest improvements such as better chemotherapy management [6,7] and modern intensity-modulated radiation therapy (IMRT) techniques, no major therapeutic progress has been made. Currently, the standard of care for non-metastatic ASCC thus relies on a combination of mitomycin and 5-fluorouracilacil-based chemotherapy (CT) and up to 59.4 Gy radiation doses to the tumor volume, with salvage APR saved in case of loco-regional relapse. This association allows for organ preservation and achieves good curative results with around 80% 5-year overall survival (OS) and excellent local control (LC) for T1-T2, N0 localized tumors. However, cure rates are lower for more advanced cases (T3-T4 or N-positive), with up to 30%-40% loco-regional or metastatic relapses, justifying the need to explore ways to improve these outcomes [8,9].  
Numerous trials have explored different hypotheses, for example, RT dose escalation to more than 60 Gy or neo-adjuvant CT in the ACCORD 03 trial [10], but all failed to demonstrate efficacy on unselected non-metastatic patients. Recent efforts aim to escalate the treatment by adding targeted therapies, epidermal growth factor receptor (EGFR) inhibitors, to classic CRT, but proof of efficacy is still lacking [11, 12, 13]. One of the foreseeable solutions is to better identify patient subgroups, in order to individualize the treatment by escalating or de-escalating it following estimated risk stratification. To this matter, large trials are being conducted like the PLATO trial (ISRCTN88455282), that aims to personalize the RT dose in three separate groups for low, intermediate and high-risk disease (ACT3, ACT4 and ACT5).  
To this day, there is no reliable way to predict which patients will experience disease recurrence following CRT. This ability to foretell response to CRT at baseline would be of significant clinical benefit, as it would allow personalized treatment and adjusted follow-up. It is trusted that novel areas of study, like radiomics and machine learning (ML), could be of critical help in better identifying upstream which patients would benefit most from treatment adjustment, justifying this critical review of the literature [14].