Esophageal cancer is a malignant tumor with a high incidence in China. At pesent, advanced esophageal cancer patients are still frequently encountered. The primary treatment for resectable advanced esophageal cancer is surgery-based multimodality therapy, including preoperative neoadjuvant therapy, such as chemotherapy, chemoradiotherapy or chemotherapy plus immunotherapy, followed by radical esophagectomy with thoraco-abdominal two-field or cervico-thoraco-abdominal three-field lymphadenectomy via minimally invasive approach or thoracotomy. In addition, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy, or immunotherapy may also be administered if suggested by postoperative pathological results. Although the treatment outcome of esophageal cancer has improved significantly in China, many clinical issues remain controversial. In this article, we summarize the current hotspots and important issues of esophageal cancer in China, including prevention and early diagnosis, treatment selection for early esophageal cancer, surgical approach selection, lymphadenectomy method, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and nutritional support treatment.
Humans ; Esophageal Neoplasms/surgery* ; Combined Modality Therapy ; Neoadjuvant Therapy/methods* ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Esophagectomy/methods*

The efficacy of surgery alone for locally advanced esophageal squamous cell carcinoma (ESCC) is limited. In-depth studies concerning combined therapy for ESCC have been carried out worldwide, especially the neoadjuvant treatment model, including neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy combined with immunotherapy (nICT), neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), etc. With the advent of the immunity era, nICT and nICRT have attracted much attention from researchers. An attempt was thus made to take an overview of the evidence-based research advance regarding the neoadjuvant therapy of ESCC.
Humans ; Esophageal Squamous Cell Carcinoma/surgery* ; Neoadjuvant Therapy ; Esophageal Neoplasms/surgery* ; Chemoradiotherapy ; Esophagectomy

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Currently, the standard of clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) for local advanced rectal cancer generally lacks pathological examination, the cCR judged by the current standard is still far from the real pathological complete response. After nCRT, due to the presence of tissue edema and fibrosis, MRI is highly uncertain in determining the staging of local lesions. The precision of colonoscopy biopsy is generally low because residual cancer foci exist primarily in the muscular layer, which limits the determination of cCR by colonoscopy biopsy. Local excision through the anus can resect the whole intestinal wall tissue, which is relatively accurate and close to the real state of remission of the lesion, but there are many problems, such as affecting anal function, high rate of complications, and increased difficulty of following radical surgery. Based on the present diagnosis of cCR, the authors put forward the concept of modified cCR (m-cCR) which combined with the pathological standard of transanal multipoint full-layer puncture biopsy. It is possible to improve the accuracy of cCR, and improve the safety of cCR patients who receive wait-and-watch therapy without increasing complications or affecting anal function. The exact conclusion needs to be confirmed by further studies.
Humans ; Neoadjuvant Therapy ; Treatment Outcome ; Neoplasm Recurrence, Local/diagnosis* ; Watchful Waiting ; Rectal Neoplasms/surgery* ; Chemoradiotherapy

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.
Antineoplastic Combined Chemotherapy Protocols ; Chemoradiotherapy/methods* ; Disease-Free Survival ; Humans ; Neoadjuvant Therapy/methods* ; Neoplasm Staging ; Neoplasms, Second Primary/pathology* ; Rectal Neoplasms/therapy* ; Rectum/pathology* ; Treatment Outcome

INTRODUCTION: We report outcomes of patients with oesophageal cancer treated with neoadjuvant chemoradiotherapy (NACRT) plus surgery or definitive chemoradiotherapy (chemoRT) at our institution. METHODS: We retrospectively reviewed patients who underwent chemoRT from 2005 to 2017. The primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS) and toxicities. RESULTS: We identified 96 patients with median age of 64 years and squamous cell carcinoma in 82.3%. Twenty-nine patients (30.2%) received NACRT plus surgery, 67 patients (69.8%) received definitive chemoRT. Median follow-up was 13.5 months. The 3/5-year OS were 26.4%/13.4%, and 59.6%/51.6% in the definitive chemoRT and NACRT plus surgery groups, respectively. The 3/5-year DFS were 19.3%/12.3%, and 55.7%/37.2% in the definitive chemoRT and NACRT plus surgery groups, respectively. NACRT plus surgery significantly improved OS (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.22-0.72, CONCLUSION NACRT plus surgery improved OS and DFS. However, in view of treatment-related complications, careful selection of patients is warranted. With the predominant histology of our cohort being squamous cell carcinoma (SCC), our results may be more relevant for those with SCC.
Chemoradiotherapy ; Esophageal Neoplasms/pathology* ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies

Local advanced gastric cancer (LAGC) accounts for a large proportion of annual newly diagnosed gastric cancer patients in China. There is a general consensus for D2 radical gastrectomy followed by postoperative adjuvant chemotherapy for LAGC patients, and this therapeutic strategy has been confirmed by a series of clinical trials to obviously improve the patients' prognosis; however, the recurrence rate is still high (about 50%-80% in advanced stage), which makes it difficult to further improve the long-term survival. Perioperative therapy, especially whether preoperative neoadjuvant therapy (NAT) can improve the efficacy of patients with LAGC, has been paid more and more attention. NAT is mainly defined as a preoperative chemotherapy or chemoradiotherapy, aiming at increasing curative resection rate by downstaging tumor, eliminating micrometastases, and autologously testing of anti-cancer drug sensitivity etc. However, there are still some controversy whether LAGC patients could gain survival benefit from NAT and also lack of general consensus for this issue. In this paper, the author reviews and analyzes the current situation of perioperative therapies for LAGC patients, especially emphasize the results of neoadjuvant chemotherapy or chemoradiotherapy reported by various high-level clinical studies. The preliminary effect of perioperative chemotherapy combined with molecular targeted or immunotherapy has also aroused great interest and attention. While we continue to carry out NAT and look forward to more new high-level evidence trials on NAT, we must emphasize again that R0 gastrectomy remains the most important therapeutic modality for the patients with LAGC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Gastrectomy/methods* ; Humans ; Lymph Node Excision ; Neoadjuvant Therapy ; Neoplasm Staging ; Perioperative Care/trends* ; Stomach Neoplasms/therapy*

Perioperative treatment is critical to improve the outcomes of patients with advanced gastric cancer. There are three therapeutic modes of perioperative treatment for resectable gastric cancer: neoadjuvant chemotherapy+ D1/D2 surgery+ adjuvant chemotherapy, D0/D1 surgery+ adjuvant radiochemotherapy, and D2 surgery+ adjuvant chemotherapy. Over the decades, a large number of clinical studies had been conducted to optimize the perioperative treatment mode of gastric cancer, including the postoperative radiotherapy and chemotherapy, and perioperative chemotherapy, and to explore the feasibility of preoperative radiochemotherapy, targeted therapy, and immunotherapy in advanced gastric cancer. After nearly 20 years of development and exploration, although the perioperative treatment mode for advanced gastric cancer has become standardized, there are still some core issues that need to be solved urgently, including the selection of population for perioperative treatment, the limitation of efficaly evaluation criteria, insufficient emphasis on laparoscopic exploration before neoadjuvant treatment, and lack of exploration in esophagogastric junction cancer. We should fully integrate the current clinical research data into clinical practice, adopt a multidisciplinary diagnosis and treatment mode, and follow the principles of standardized diagnosis and treatment based on a multi-dimensional analysis of patient characteristics, and formulate the most reasonable treatment strategy to ultimately benefit patients.
Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Esophagogastric Junction ; Gastrectomy ; Humans ; Lymph Node Excision ; Neoadjuvant Therapy ; Perioperative Care ; Stomach Neoplasms/therapy*

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.
Adenocarcinoma/therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Capecitabine/administration & dosage* ; Chemoradiotherapy, Adjuvant ; Esophagogastric Junction/surgery* ; Gastrectomy ; Humans ; Lymph Node Excision ; Neoadjuvant Therapy ; Neoplasm Staging ; Oxaliplatin/administration & dosage* ; Prognosis ; Prospective Studies ; Retrospective Studies ; Stomach Neoplasms/therapy*

The goal of rectal cancer treatment should be to better protect organ function and improve patients' quality of life on the basis of ensuring radical resection. The current evidence has proved the superiority of perioperative chemoradiotherapy in reducing local recurrence and improving long-term survival. From the perspective of organ function protection, however, perioperative chemoradiotherapy has both disadvantages and advantages. Despite the great help in improving long-term outcomes, adverse reactions of chemoradiotherapy can aggravate defecation, urination and sexual dysfunction. Also, for patients with significant or complete remission, if the treatment strategy of local resection or close follow-up is selected, organ function can be preserved to the greatest extent. The key to the choice of treatment is to evaluate preoperatively whether pathological complete response is achieved. It should be kept in mind that preserving organ itself is not the same as protecting organ function. For patients who need perioperative chemoradiation, the optimal treatment methods should be chosen based on the patient's condition. Surgeons should fully evaluate organ function before operation, select the appropriate treatment strategy, pay special attention to the protection of important organs and nerves during surgeries, and carry out close postoperative follow-up and organ function rehabilitation as soon as possible, so as to reduce the incidence of dysfunction and the impact on the quality of life.
Chemoradiotherapy ; Humans ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Quality of Life ; Rectal Neoplasms/surgery* ; Treatment Outcome ; Watchful Waiting