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Prophylactic para-aortic radiotherapy (PART) can mitigate the risk of para-aortic recurrence in locally advanced cervical cancer (LACC). However, target volume delineation for the para-aortic region is inconclusive. Based on studies evaluating the mapping of para-aortic nodes, margin expansions around the aorta and inferior vena cava (IVC) were suggested to achieve coverage of para-aortic region. However, anatomic principles that govern the distribution of lymphatics may more accurately define the para-aortic regions that determine the effectiveness and potentially reduce the dose to the intestine and further lower incidence of gastrointestinal (GI) toxicity. This study aimed to compare patient-reported GI toxicity and outcomes between anatomy- and margin-based prophylactic PART in patients with LACC.

We reviewed data of 160 patients with LACC who underwent CCRT with prophylactic PART during 2014–2019 at two tertiary medical centers. Para-aortic regions were drawn by margin expansion of 7–10 mm around aorta and IVC or anatomic para-aortic region atlas published by Takiar et al. (Figure 1). The upper border of PART was at the level of left renal vein. The prescribed dose of PART was 45 Gy. Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was used to assess acute GI toxicity. Vx indicated the volume (mL) of small bowel or duodenum that received a radiation dose of x Gy.

Eighty-four and 76 patients received margin-based and anatomy-based PART, respectively. Median follow-up time was 40.1 months (IQR: 25.5–58.9). The V45 and V30 of small bowel and duodenum were significantly lower in the anatomy-based PART group compared with margin-based PART group (small bowel, V45: 159.6 ± 32.8 vs. 188.7 ± 47.4, p<0.001; V30: 615.3 ± 131.0 vs. 742.6 ± 127.1, p<0.001; duodenum, V45: 8.3 ± 3.9 vs. 16.1 ± 5.9, p<0.001; V30: 19.8 ± 6.2 vs. 26.9 ± 6.4, p<0.001, respectively). The V15 of small bowel and duodenum were not significantly different between groups. Patients who received anatomy-based PART experienced significantly less patient-reported severe toxicity (PRO-CTCAE score ≥3) than patients who received margin-based PART in terms of frequency of diarrhea (7.9% vs. 20.2%; p=0.03), severity of abdominal pain (3.9% vs. 14.3%; p=0.03), and interference of abdominal pain (2.6% vs. 11.9%; p=0.03). The patterns of failures were not different between groups (Table 1). The sites of PALN failures of these two patients were above the level of left renal vein. There was no in-field or marginal PALN failure in these two groups. The 3-year overall survival and disease-free survival for margin-based PART vs. anatomy-based PART were 80.9% vs. 84.9% (p=0.61) and 71.8% vs. 77.4% (p=0.47), respectively.

Anatomy-based PART can reduce the dose-volume to the small bowel and duodenum, and lower the incidence of severe patient-reported GI toxicity. The patterns of failure and survival outcomes were similar between para-aortic delineations.