Clinicopathological Features, Clinical Efficacy on 101 Cases of Rectal Gastrointestinal Stromal Tumors, and the Significance of Neoadjuvant Therapy

Objective: To investigate the clinicopathological features, clinical efficacy on 101 cases of rectal gastrointestinal stromal tumors (GISTs), and the significance of Imatinib Mesylate (IM) neoadjuvant therapy.Methods: The clinicopathological features, treatment methods, peri-operative data, and prognosis of the patients were summarized and analyzed on 101 patients with rectal GISTs, who received treatment in the Gastrointestinal Department of West China Hospital of SichuanUniversity and the Affiliated Hospital of Guizhou Medical University from August 2002 toNovember 2020 in China. Results: A total of 101 patients, including 64 males and 37 females, were aged from 22 to 79 years (55.4±12.2 years). Among 70 patients with direct surgery, which included 8 very low risk cases, 10 low risk cases, 7 intermediate risk cases, and 45 high risk cases. Cox regression analysis showed that post-operative IM adjuvant treatment improved disease-free survival (DFS) and overall survival (OS) of 52 intermediate and high risk patients. Among the 31 patients who received neoadjuvant therapy, the objective response rate (ORR) was 83.9% (26/31), and the disease control rate (DCR) reached 96.8% (30/31). Diameter subgroup analysis: (1) Among the 36 patients with a diameter ≤ 5 cm, two patients received IM neoadjuvant therapy, while 34 patients received direct surgery. Both univariate and Cox regression analysis did not find that neoadjuvant therapy affects DFS and OS. (2) Among the 65 patients of diameter >5 cm, 29 received IM neoadjuvant therapy and 36 received direct surgery. Patients who underwent neoadjuvant therapy had less blood loss (P=0.022) , shorter post-operative hospital stay (P=0.001), increased anal preservation proportion (93.1% VS72.2% , P=0.031), decreased enterostomy proportion (10.3% VS 33.3%, P=0.037) than those who underwent direct surgery. Cox regression analysis suggested that neoadjuvant therapy and post-operative IM adjuvant therapy improved DFS. Conclusion: Rectal GISTs is relatively rare and is a highly malignant tumor, post-operative oral IM therapy can improve DFS and OS of intermediate and high risk patients. In patients with rectal GISTs with diameter > 5 cm, IM neoadjuvant therapy can improve the anal preservation proportion , preserve the structure and function of the organs, reduce enterostomy proportion, and improve prognosis.

ISR for T1-2 Low Rectal Cancer: A Japanese Approach

The evolution over the past 20 years of anal preservation in rectal cancer surgery has been truly remarkable. Intersphincteric resection (ISR) reported by Schiessel in 1994 in Australia has been shown to enable anal preservation even for cancers quite close to the anus. In Japan, ISR via the detachment of the anal canal between the internal and external sphincters and excision of the internal sphincter first began to be practiced in the latter half of 1990. A multicenter Phase II trial of ISR in Japan suggested that 70% of the cases had relatively good function with less than 10 points of Wexner score but around 10% had severe incontinence that would not be improved for long term. The primary end point of the clinical study, 3-year local recurrence rate, was 13.2% across the overall cohort (T1, 0%; T2, 6.9%; and T3, 21.6%). When ISR is performed on T1/T2 rectal cancers, sufficient circumferential resection margin can be obtained even without preoperative chemoradiotherapy, and local recurrence rate was acceptably low. Based on these evidences, ISR is a currently important, standard treatment option among anal-preserving surgeries for T1/T2 low-lying rectal cancers. In Japan, a feasibility study (LapRC trial) of laparoscopic ISR on Stage 0 and Stage 1 low rectal cancer showed excellent outcomes. A prospective Phase II clinical trial targeting low rectal cancers within 5 cm from the anal verge (ultimate trial) is being performed and awaiting the results in near future.

Preoperative radiotherapy combined with simultaneous chemotherapy with capecitabine plus oxaliplatin versus surgery alone: A single-centered, phase II study in patients with mid/low rectal cancer.

609 Background: Though total mesorectal excision (TME) has proved to effectively decrease local recurrence rate of mid/low rectal cancer, the efficacy of preoperative radiotherapy in Asian patients remains unclear. The present study aimed to compare the efficacy of TME alone versus TME after preoperative radiotherapy and simultaneous chemotherapy with capecitabine plus oxaliplatin in Chinese patients with stage II and III mid/low rectal adenocarcinoma. Methods: Patients (n=192) aged between 18 and 70 years enrolled from March 23, 2008 to August 2, 2012 were randomly divided into two groups. Group A (n=97) received preoperative radiotherapy and simultaneous chemotherapy [46-50 GY/23-25 with oxaliplatin 100 mg/m2 (D1) and capecitabine 1,000 mg/m2 (bid, D1-15), repeated since D22], which was followed by TME; while patients in group B (n=95) underwent TME alone. While disease free survival (DFS) was the primary endpoint; the following were evaluated as secondary endpoints: pathological response rate, pathologic complete response (PCR) rate, anal preservation rate, local recurrence rate, distant metastasis rate, acute toxic effects, and late toxic effects. Results: Excluding the drop outs, 90 and 94 patients were analyzed in group A and B, respectively. The median follow-up time was 29 (range: 0 to 59) months. PCR was achieved for 32 patients (35.6%). The median survival time and overall survival (OS) rate in group A were 24 months and 92.5% (95% CI: 88.3-96.7), respectively; while the same were 34 months and 88.7% (95% CI: 84.8-92.6) in group B. The median DFS time was 22 and 31 months in group A and B, respectively; and the overall DFS was 86.1% (95% CI: 81.6-90.6%) and 80.6% (95% CI: 74.8-85.4%) in both groups. No significant differences were observed between groups in OS rate (p=0.323), overall DFS, (p=0.612), and anal preservation rate (p=0.849). Conclusions: Preoperative radiotherapy combined with chemotherapy of capecitabine plus oxaliplatin could result in higher PCR rate. However, studies with long follow up and large sample are recommended to demonstrate the efficacy of this treatment strategy over TME alone. Clinical trial information: ChiCTR-TRC-00000122.