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In the current study we analysed the dosimetric data on patients enrolled in a prospective phase II study on volume de-escalation in neoadjuvant chemoradiotherapy (CRT) of locally advanced rectal cancer (LARC) compared to an historical matched-control patient group.

This study included 103 patients with LARC (T2 low-lying/T3, N0-N1) and compared a prospective group with an historical group. Fifty-two patients were enrolled in the prospective study. De-escalated treatment volumes, due to the exclusion of elective nodal irradiation, were delineated. The CTV included the primary tumor and mesorectum with vascular supply containing the perirectal and presacral nodes. The PTV was defined by the CTV with a margin of 1 cm in all directions. Radiation therapy was delivered with a total dose of 50.4 (28fx/1.8Gy) using 3-dimensional conformal techniques. The control group (51 patients) received standard treatment. In both, concomitant fluoropyrimidine-based chemotherapy was associated. We analysed dose parameters of the main organs at risk (OARs) for the two groups (reduced vs standard volumes): small bowel (V5, V10, V15, V20, V30, V45), bladder (Dmax, V5, V10, V15, V35, V50) and femoral heads (V52). Treatment interruptions (≥ 5 days) due to adverse events were the primary clinical endpoint of this analysis. The dosimetric variables were compared using the independent sample t-test. A 2-sided p value of 0.05 was considered significant.

The mean volume of de-escalated PTV was 495.5cc ± 169.8cc (range, 231.0cc– 920.3cc) compared with standard PTV (mean 1055.37cc ± 204.44cc; range, 620.6cc – 1696.9cc). The V5, V10, V15, V20, V30, V45 of small bowel were significantly lower in the reduced volumes group (mean 170.9cc, 131.8cc, 54.1cc, 35.2cc, 25.5cc, 13.4cc respectively), in comparison with the standard group (mean 531.3cc, 429.4cc, 302.0cc, 231.8cc, 139.3cc, 60.2cc respectively; p<0.001). The Dmax, V5, V10, V15, V35, V50 of the bladder were also significantly lower in the experimental group (mean 65.7Gy, 94.1%, 90.4%, 65.3%, 13.1%, 2.5% respectively) than in the control group (mean 55.9Gy, 100.6%, 99.2%, 94.1%, 56.7%, 6.6% respectively; p<0.033). Moreover, the left and right femoral heads V52Gy was lower in the first group (p=0.042). Treatment interruptions due to gastrointestinal toxicity in the two groups was 11.5% vs 41.1%, respectively (p=0.001).

This is the first study to show significant dose reduction for OARs given by the reduction of target volume in LARC compared to the historical group, while improving clinical outcomes as shown in the final report of the study protocol. This is probably related to the biological effect associated with the low number of interruption days and to the early stage of the selected population.