Total neoadjuvant treatment to increase the clinical complete response rate for distal locally advanced rectal cancer (TESS): A study protocol of a prospective, open-label, multicenter, single-arm, phase 2 trial.

BACKGROUND: Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open-label, multicenter, single-arm, phase 2 study, is underway. METHODS: Main inclusion criteria include cT3-4aNany or cT1-4aN+ rectal adenocarcinoma aged 18-70y; Eastern Cooperative Oncology Group (ECOG) performance 0-1; location ≤5 cm from anal verge. Ninety-eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease-free survival; locoregional recurrence-free survival; acute toxicity; surgical complications; long-term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment. DISCUSSION: The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

CLK2 Expression Is Associated with the Progression of Colorectal Cancer and Is a Prognostic Biomarker.

Background: CLK2 is a splicing regulator and expressed ubiquitously in various malignancies. The study is aimed at exploring the potential roles of CLK2 in the development of colorectal cancer (CRC). Methods: Real-time PCR and analyses of The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) database were utilized to evaluate the CLK2 gene transcription level and protein level of colorectal cancer (CRC) tissue. The chi-squared and logistic regression tests were used to evaluate the relationship between CLK2 and clinicopathologic features. Kaplan-Meier survival curve and Cox regression analysis were performed to explore the prognostic significance of CLK2. The association between CLK2 expression and immune landscapes was explored by CIBERSORT and ESTIMATE. Furthermore, GSEA (Gene Set Enrichment Analysis) and alternative splicing (AS) analyses were performed to investigate the relationship between CLK2 expression and downstream signaling pathway. Results: The CLK2 expression was upregulated in CRC in both transcript and protein level. The elevated expression of CLK2 was correlated with local invasion and poor prognosis. Furthermore, CLK2 induced tumor cell adhesion and thereby promotes local invasion of CRC. The CLK2 expression significantly inhibited plasma cells and eosinophil infiltration and showed no relationship with immune and stromal scores of CRC samples. CLK2 might involve in Notch signaling pathway by regulating the AS of CTBP1. Conclusions: CLK2 might be a potential prognostic biomarker and therapeutic target for colorectal cancer.

[Surgical treatment of Siewert II adenocarcinoma of the esophagogastric junction].

OBJECTIVE: To explore the outcomes after surgical treatment of esophagogastric junction carcinoma (EGJC). METHODS: One hundred and eighty-five patients with EGJC undergoing surgery from October 2000 to September 2006 at the Cancer Hospital of Shantou University were reviewed retrospectively. The clinical outcomes were compared between transthoracic and transabdominal approach. RESULTS: Of the 185 patients, 133 underwent operation via transthoracic approach and 52 via transabdominal approach. The postoperative complication rates were 10.5%(14/133) and 11.5%(6/52) and the 1-, 3-, 5-year overall survival rates were 83.9%, 44.5%, 32.9% and 86.0%, 38.0%, 30.0% in transthoracic and transabdominal groups respectively, and the difference were not statistically significant (both P>0.05). CONCLUSION: Surgical approach should be individualized for EGCJ.