Acute toxicities of patients with locally advanced rectal cancer treated with intensified chemoradiotherapy within the CAO/ARO/AIO-12 trial: comparing conventional versus VMAT planning at a single center

Abstract

In locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is regarded as standard treatment. We assessed acute toxicities in patients receiving conventional 3D-conformal radiotherapy (3D-RT) and correlated them with dosimetric parameters after re-planning with volumetric modulated arc therapy (VMAT). Patients were randomized within the multicenter CAO/ARO/AIO-12 trial and received 50.4 Gy in 28 fractions and simultaneous chemotherapy with fluorouracil and oxaliplatin. Organs at risk (OAR) were contoured in a standardized approach. Acute toxicities and dose volume histogram parameters of 3D-RT plans were compared to retrospectively calculated VMAT plans. From 08/2015 to 01/2018, 35 patients with LARC were treated at one study center. Thirty-four patients were analyzed of whom 1 (3%) was UICC stage II and 33 (97%) patients were UICC stage III. Grade 3 acute toxicities occurred in 5 patients (15%). Patients with acute grade 1 cystitis (n = 9) had significantly higher Dmean values for bladder (29.4 Gy vs. 25.2 Gy, p < 0.01) compared to patients without bladder toxicities. Acute diarrhea was associated with small bowel volume (grade 2: 870.1 ccm vs. grade 0–1: 647.3 ccm; p < 0.01) and with the irradiated volumes V5 to V50. Using VMAT planning, we could reduce mean doses and irradiated volumes for all OAR: Dmean bladder (21.9 Gy vs. 26.3 Gy, p < 0.01), small bowel volumes V5–V45 (p < 0.01), Dmean anal sphincter (34.6 Gy vs. 35.6 Gy, p < 0.01) and Dmean femoral heads (right 11.4 Gy vs. 25.9 Gy, left 12.5 Gy vs. 26.6 Gy, p < 0.01). Acute small bowel and bladder toxicities were dose and volume dependent. Dose and volume sparing for all OAR could be achieved through VMAT planning and might result in less acute toxicities.

THeragnostic utilities for neoplastic DisEases of the rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: interim safety analysis

“…The most common toxicities of nCRT treatment for LARC have already been widely evaluated in several studies. They often seem to correlate with the synergistic effect of CHT and depend significantly on the volume of healthy tissue irradiated [ 23 ].…”

THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy (THUNDER 2) phase II trial: Interim Safety Analysis

“…The most common toxicities of nCRT treatment for LARC have already been widely evaluated in several studies. They often seem to correlate with the synergistic effect of chemotherapy and depend signi cantly on the volume of healthy tissue irradiated [23].…”