Total neoadjuvant therapy using short course radiation with or without SIB to lateral pelvic lymph nodes in locally advanced ugly rectal cancer.
Authors: RAHUL KRISHNATRY, Aditi Jain, Mufaddal Khuzema Kazi, Shivakumar Gudi, Devankshi Rane, Purva Pawar, Anant Ramaswamy, Prabhat Ghanshyam Bhargava, Purvi Haria, Suman Kumar, Mukta Ramadvar, Vikas S. Ostwal, Avanish Saklani, Reena Engineer
Journal: Journal of Clinical Oncology (2024)

30 Background: Optimal management for lateral pelvic lymph nodes (LPLN) in Ugly locally advanced rectal cancer (LARC) is unknown &amp; is associated with worse outcomes. We hypothesise that total neo-adjuvant (TNT) using Short-course radiotherapy (SCRT) with SIB to lateral pelvic lymph nodes would improve outcomes. Methods: All consecutive patients of LARC with LPLN treated with SCRT-based TNT from Jan 2021 – Dec 2022 were reviewed (IEC No: 4116). The LPLN (external, internal, common iliac or obturator) was considered radiologically significant based on joint clinic review with classical criteria. They were divided into two groups (SIB-IMRT: up to 30Gy/5#; or not). The chemotherapy schedule was similar to RAPIDO study, followed by TME +/- LPLN dissection based on radiological response assessed in joint clinic. Two groups were compared for baseline features using Fisher’s exact/Chi-Square tests as appropriate. Outcomes were reviewed for overall response in LPLN (radiological or pathological), disease outcomes &amp; toxicity (acute radiotherapy CTCAE v5, 30-day Clavien Dindo post-surgical, &amp; HRQL EOTRC QLQ-C30). Results: From 398 patients, 83 (20.8%) were identified with LPLN receiving SCRT with TNT, of which 44 (53.01%) received a SIB boost. Overall, 40% were aged ≤ 45 years, 50% had poor histology (signet, PDAC, Mucinous), 35% had EMVI, and 83% were N2+. The two groups had a similar distribution of baseline features (p&gt;0.05) &amp; were matched for poor prognostic factors. The patients who received a boost were 20% more likely to complete TNT and undergo TME than patients who did not (81.8% vs 61.5%; p=0.0099), mainly due to a significantly lesser event of disease progression before surgery, rendering them inoperable (25% vs 33.3%; p=0.024). Boost was associated with an increased overall response at LPLN by 20% (84.1% vs 64.1%; p=0.011) &amp; decreased need for PLND by 15% in patients considered for surgery (15.9% vs 30.56%; p=0.072). At a median follow-up of 18 months, 26 patients (31.33%) identified with disease progression were similarly distributed in two groups with similar patterns (all but one had distant metastasis, of which 6 had loco-regional failures). A total of 17 deaths with a non-significant trend of higher 18-month OS observed (boost: 83.4+6.3 vs 75.6+7.8%; HR:2.29(CI:0.85 - 6.19; p=0.09). None of the patients had acute &gt; grade 3 CTCAE v5 toxicity within 4 weeks of radiotherapy completion. Four (4.8%) deaths were chemotherapy-related, &amp; one post-surgery toxicity with similar &gt; grade 3 Clavien Dindo complications in two arms. EORTC QLQ C-30 PROM scores were similar in two groups. Conclusions: In ugly, poor biology LARC, TNT with SCRT-SIB to LPLN seem safe &amp; feasible with improved response, treatment completion &amp; operability without significantly increase in toxicity rates. Long-term prospective studies are warranted to identify significant survival impact.