TY  - JOUR
AU  - Gani, Cihan
AU  - Fokas, Emmanouil
AU  - Polat, Bülent
AU  - Ott, Oliver J
AU  - Diefenhardt, Markus
AU  - Königsrainer, Alfred
AU  - Böke, Simon
AU  - Kirschniak, Andreas
AU  - Bachmann, Robert
AU  - Wichmann, Dörte
AU  - Bitzer, Michael
AU  - Clasen, Stephan
AU  - Grosse, Ulrich
AU  - Hoffmann, Rüdiger
AU  - Götz, Martin
AU  - Hofheinz, Ralf-Dieter
AU  - Germer, Elisabeth
AU  - Germer, Christoph-Thomas
AU  - Fietkau, Rainer
AU  - Martus, Peter
AU  - Zips, Daniel
AU  - Rödel, Claus
TI  - Organ preservation after total neoadjuvant therapy for locally advanced rectal cancer (CAO/ARO/AIO-16): an open-label, multicentre, single-arm, phase 2 trial.
JO  - The lancet / Gastroenterology & Hepatology
VL  - 10
IS  - 6
SN  - 2468-1253
CY  - London
PB  - Elsevier
M1  - DKFZ-2025-00968
SP  - 562 - 572
PY  - 2025
AB  - Total neoadjuvant therapy has been shown to increase pathological complete response and disease-free survival in patients with locally advanced rectal cancer after total mesorectal excision (TME). We hypothesised that total neoadjuvant therapy could maximise the number of patients attaining a clinical complete response who could then be instead referred to organ preservation with watch and wait.This open-label, multicentre, single-arm, phase 2 study (CAO/ARO/AIO-16) was conducted at four centres across Germany. Patients aged 18 years or older with histologically confirmed cT1-2N1-2 or cT3a-dN0/N1-2 rectal adenocarcinoma up to 12 cm from the anal verge and without distant metastases received chemoradiotherapy. Radiotherapy was administered in daily fractions of 1·8 Gy, 5 days per week, starting at day 1 and ending at day 38, for a total of 28 fractions and total dose of 50·4 Gy. Concomitant fluorouracil (250 mg/m2 per day as a continuous venous infusion from day 1 to day 14 and day 22 to day 35) and oxaliplatin (50 mg/m2 intravenously on days 1, 8, 22, and 29) were administered. Chemoradiotherapy was followed by three cycles of consolidation FOLFOX (fluorouracil [2400 mg/m2 over 46 h by continuous venous infusion], oxaliplatin [100 mg/m2 intravenously as a 2-h infusion], and leucovorin [400 mg/m2 intravenously as a 2-h infusion]) starting on days 57, 71, and 85. Response assessment was scheduled on day 106 after the start of total neoadjuvant therapy and included digital rectal examination, rectoscopy, and pelvic MRI. In case of a clinical complete response, patients were scheduled for a watch and wait surveillance protocol. Patients with a near clinical complete response on day 106 were offered a second assessment on day 196. In case of conversion to a clinical complete response on this repeated assessment, the same watch and wait surveillance protocol was initiated. Alternatively, local excision was considered on day 196 if technically feasible. In all other cases, immediate TME surgery was recommended. The primary endpoint was the clinical complete response rate on day 106 or 196 assessed in patients who started chemoradiotherapy (intention-to-treat population). Toxicity was also assessed in this patient population. The study was registered with ClinicalTrials.gov (NCT03561142) and is complete.Between June 1, 2018, and Oct 7, 2020, we enrolled 93 patients, of whom 91 (mean age 61 years [SD 10]; 61 [67
KW  - Humans
KW  - Rectal Neoplasms: therapy
KW  - Rectal Neoplasms: pathology
KW  - Neoadjuvant Therapy: methods
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Aged
KW  - Adenocarcinoma: therapy
KW  - Adenocarcinoma: pathology
KW  - Fluorouracil: administration & dosage
KW  - Fluorouracil: therapeutic use
KW  - Antineoplastic Combined Chemotherapy Protocols: therapeutic use
KW  - Antineoplastic Combined Chemotherapy Protocols: administration & dosage
KW  - Organ Sparing Treatments: methods
KW  - Oxaliplatin: administration & dosage
KW  - Adult
KW  - Chemoradiotherapy
KW  - Chemoradiotherapy, Adjuvant
KW  - Leucovorin: administration & dosage
KW  - Watchful Waiting
KW  - Fluorouracil (NLM Chemicals)
KW  - Oxaliplatin (NLM Chemicals)
KW  - Leucovorin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40347958
DO  - DOI:10.1016/S2468-1253(25)00049-4
UR  - https://inrepo02.dkfz.de/record/301283
ER  -