Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer

Abstract

for the German Rectal Cancer Study Group IMPORTANCE Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. OBJECTIVE To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population

Evaluation of Efficacy and Tolerance of Radical Radiotherapy and Radiochemotherapy in Treatment of Locally Advanced, Unresectable Rectal Cancer

“… 53 On the other hand, CAO/ARO/AIO-12 study revealed that CRT followed by consolidation chemotherapy led to higher rates of pathological complete response compared with induction. 54 Aforementioned clinical trials are designed for pts in good PS. Such prolonged TNT may be for some pts unbearable.…”

Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview

“…Short-term results of CAO/ARO/AIO-12 and OPRA trials showed improved pCR and cCR, improved compliance to CRT and grade 3 to 4 toxicity rate reduction, when comparing consolidation and induction TNT [ 38 , 39 ]. Recently, the CAO/ARO/AIO-12 trial long-term results confirmed consolidation TNT safety in terms of oncological endpoints, chronic toxicity, quality of life and stool incontinency [ 40 ]. However, long-term results in terms of 3-years disease free survival (DFS) from the phase 2 randomized OPRA trial are still awaited.…”

“…All of these and also infectious complications, which were particularly relevant in the RAPIDO trial [ 30 ], are reported in the most recent meta-analyses demonstrating the higher risk of developing also serious (Grade III/IV) AEs for TNT patients [ 32 , 45 ]. Moreover, the CAO/ARO/AIO-12 trial showed grade 3–4 AEs during CRT were more frequent in the induction group compared to the consolidation group [ 40 ].…”

Debating Pros and Cons of Total Neoadjuvant Therapy in Rectal Cancer

“…For instance, the hypoxic and acidic TME as a consequence of CRT is responsible for slowing down cell cycling, down-regulating DNA damage responses, reducing apoptosis, and increasing autophagy properties [ 82 ]. A series of in vitro experiments in CRC cell lines showed that low oxygen levels result in a decreased expression of pro-apoptotic proteins and contribute to resistance to oxaliplatin [ 83 ]. Another study reported the association between aerobic glycolysis and 5-FU resistance [ 84 ].…”