Exploration of feasible total neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Neoadjuvant radiotherapy and chemotherapy combined with surgery is the standard treatment for patients with locally advanced esophageal cancer, which has been widely applied in clinical practice. Clinical efficacy has also been recognized by clinicians. However, even after the completion of neoadjuvant radiotherapy and subsequent surgical treatment, some patients still have local regional recurrence or distant metastasis in a short period of time. Among them, distant metastasis has become the main failure mode of patients undergoing surgery after neoadjuvant radiotherapy and chemotherapy, indicating that this treatment remains to be further improved. Based on the experience of patients with rectal cancer benefiting from total neoadjuvant therapy, the feasibility and implementation of total neoadjuvant therapy for locally advanced esophageal cancer were discussed in this article.

Sphincter preservation operation and comprehensive treatment for ultra-low rectal cancer / 中华消化外科杂志

In the past 20 years, the multidisciplinary treatment model based on evidence-based medicine has significantly increased the rate of sphincter-preservation operation for rectal cancer. How to preserve rectum and anal function, avoid permanent colostomy, and improve post-operative quality of life of patients while ensuring radical resection of tumor, remains to be a key and hot topic in surgical treatment of rectal cancer. Based on literatures and clinical experiences, the authors summarize issues of sphincter preservation operation and comprehensive treatment, including intersphincteric resection, conformal sphincter preservation operation, total neoadjuvant therapy and radioimmunotherapy, for ultra-low rectal cancer, in order to provide reference for the colleagues.

Efficacy and safety of total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.

Current status and challenges of total neoadjuvant therapy for pancreatic cancer / 中华消化外科杂志

With the development of neoadjuvant therapy, the treatment of pancreatic cancer has entered the era of comprehensive diagnosis and treatment consisting of surgery, chemo-therapy and radiotherapy. In recent years, the concept of 'total neoadjuvant therapy' has become one of the important treatment methods for locally advanced rectal cancer. The authors focus on pancrea-tic cancer, introduce the development status of total neoadjuvant therapy in pancreatic cancer and summarize the current controversies and challenges in the application of total neoadjuvant therapy in pancreatic cancer, in order to further standardize the diagnosis and treatment of pancreatic cancer and improve the overall level of pancreatic cancer treatment in China.

Advances of optimized neoadjuvant therapy in the treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Neoadjuvant chemoradiotherapy is the current standard of care for locally advanced rectal cancer. However, this modality is facing more and more challenges. The research progress on this issue around the world can be summarized into three aspects. The first is to increase the intensity of treatment to obtain better tumor regression, such as adding a second drug during the neoadjuvant chemoradiotherapy, prolonging the interval and receiving sufficient chemotherapy before surgery. Current research data are not sufficient to support strategies for adding drugs or receiving sufficient chemotherapy before surgery, but it may be worth looking forward to adding irinotecan during neoadjuvant chemoradiotherapy, and an appropriate extension of the interval before surgery may also be a good option. Secondly, we can reduce the intensity of treatment to improve the quality of life of patients with a non-inferior clinical outcome, such as non-surgical approach, local excision rather than total mesorectal excision and removal of preoperative radiotherapy. The data of the International Watch & Wait Database (IWWD) suggest that patients with a Watch & Wait strategy have similar long-term survival outcomes as those who have undergone surgery and have pathologic complete response, meanwhile the data are still inadequate to support using local excision instead of total mesorectal excision, or removal of preoperative radiotherapy strategies. Finally, to achieve a precise individual treatment, some potential biomarkers are investigated via genomics, metabolomics and radiomics. But so far, there is no recognized biomarker for clinical treatment in the field of neoadjuvant therapy for rectal cancer. This article summarizes the clinical research progress of locally advanced rectal cancer in recent years from the above three aspects.

Transition of treatment strategy for locally advanced rectal cancer towards "watch and wait" / 中华胃肠外科杂志

Therapeutic goal for locally advance rectal cancer (LARC) patients includes long-term survival and function preservation of pelvic organs. During the recent two decades, treatment strategy for LARC is gradually shifing to minimally invasive surgery, even avoiding a major surgery. "Watch and wait (W&W)" strategy is effective in dramatically decreasing surgical trauma and significantly improving preservation of defecation, urination and sexual function. Total neoadjuvant therapy (TNT) shifts all or part of adjuvant chemotherapy to the neoadjuvant phase and has showed obvious advantage in tumor shrinkage and complete clinical response (cCR) achievement. This article will summarize the transition of treatment strategy of LARC towards W&W from standard treatment. After more than ten years of development, both NCCN and ESMO guidelines recommend stratified neoadjuvant treatment considerations based on distinct risk classifications and especially suggest TNT for LARC patients with advanced diseases, which affirms the value of TNT in tumor shrinkage. Although accumulating data show that pelvic control and organ preservation using W&W strategy after cCR is equal or non-inferior to standard surgery, impact on long-term survival still needs prospective randomized controlled study; no consensus has been achieved for the detail of the W&W strategy. Thus W&W strategy is suggested to applied in hospitals specialized in the treatment of rectal cancer within the framework of multiple disciplinary treatment. In view of special medical conditions of our country, we still need to accumulate more experience and data of W&W strategy for rectal cancer patients with appeals for sphincter preservation and actively participate in international researches.

Analysis on efficacy and safety of total neoadjuvant therapy in patients with locally advanced rectal cancer with high risk factors / 中华胃肠外科杂志

Objective@#To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors.@*Methods@#Data of 101 patients who were diagnosed with stage II-III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II-III rectal cancer by high-resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+ and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm; (4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0-1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow-up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch-and-wait strategy was selected according to the therapeutic effect and patients' wishes. Short-term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed.@*Results@#The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0±1.3. Seventy-five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0±0.9 and 2.8±1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch-and-wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3.@*Conclusion@#TNT is safe and has good short-term efficacy for locally advanced rectal cancer patients with high risk factors.