Planned Non-operative Management for Rectal Cancer

Radio(Chemo)Therapy Dose Escalation in Non-operative Management for Rectal Cancer: A Prospective NOM-3 Observational Study

The investigators propose to conduct an observational study on consecutive patients with low-lying or mid rectal cancers smaller than 5 cm in length and less than 50% of rectal circumferential extent. The aim of this study is to test a hypothesis that escalation of either radiation or chemotherapy dose of the routine preoperative radio(chemo)therapy leads to an increase of clinical complete response rate. The planned sample size of 23 patients was calculated based on the assumption that clinical complete response rate after routine preoperative radio(chemo)therapy is 34% [1] and expected rate after radio(chemo)therapy dose escalation is 75% [2-4]. An endorectal high dose rate iridium brachytherapy boost (2 fractions of 10 Gy) will be added after the routine preoperative treatment consisted of external beam radiotherapy (5 × 5 Gy) combined with sequential 3 cycles of consolidation FOLFOX4. However, for patients with involvement of the anal canal, additional 3 cycles of consolidation FOLFOX4 (6 cycles in total) will be added instead of brachytherapy boost to avoid severe post-radiation toxicity.

Additional three cycles of consolidation chemotherapy consisted of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4).

Three additional cycles of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4) consolidation chemotherapy

Clinical complete response will be assessed by digital rectal examination, endoscopy and MRI. The analysis will take place 6 months after the start of treatment of a last enrolled patient.

Regrowth rate will be accessed at 2 years in patients undergoing watch-and-wait. The analysis will take place 12 months after the start of treatment of a last enrolled patient.

Anorectal function will be assessed by LARS scale before treatment and one year after the radiation start.

Acute and late toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE), version 5.

Inclusion Criteria: Adenocarcinoma of the rectum classified clinically as T2, T3a-c or T4b but only with superficial infiltration of the vagina or prostate; tumour accessible by digital rectal examination; tumour ≤5 cm in length and ≤50% of rectal circumferential extent; N0-N2, but mesorectal node <7 mm and no lateral nodes enlargement); extramural vascular invasion but not larger than 7 mm in the largest dimension; M0. Operable patient Patient having read the information note and having signed the informed consent Follow-up possible Exclusion Criteria: Inoperable patient cT1, cT3d, large T4, tumour ≥5cm or ≥50 of rectal circumferential extent Enlargement of lateral nodes or any node ≥8 mm in diameter Patient presenting metastasis at diagnosis Previous pelvic irradiation Simultaneous progressive another cancer Close follow-up uncertain.

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Rijkmans EC, Cats A, Nout RA, van den Bongard DHJG, Ketelaars M, Buijsen J, Rozema T, Franssen JH, Velema LA, van Triest B, Marijnen CAM. Endorectal Brachytherapy Boost After External Beam Radiation Therapy in Elderly or Medically Inoperable Patients With Rectal Cancer: Primary Outcomes of the Phase 1 HERBERT Study. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):908-917. doi: 10.1016/j.ijrobp.2017.01.033. Epub 2017 Jan 20.

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