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.

Effect evaluation of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

Retrospective analysis on 77 cases of T4b hypopharyngeal carcinoma treated by non-surgical treatments / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.

Proteinemia as a Prognostic Factor in Colorectal Cancers beyond Surgery and Chemotherapy

Background: Globally, 1,096,601, 704,376, and 48,541 new colon, rectum, and anus cancer cases were recorded in 2018, respectively. Besides, 551,269, 310,394 and 19,129 cases of colon, rectum, and anus cancer deaths occurred in the same year. As a result, these cancers ranked in the third level of cancer incidence, and in the second level of cancer mortality. As it is known, all cancer patients are subjected to cancerinduced and therapy-induced nutritional deficiencies (mainly of proteins and calories). The present study aimed to assess proteins level in colorectal cancer (CRC) patients who underwent surgery and chemotherapy. Methods: A combined retrospective and prospective study was performed. The present study enrolled 100 CRC patients with their data on surgical procedures and chemotherapy management. Assessments of the studied samples were conducted as a baseline before receiving chemotherapy and preoperatively as P0, while the period after that was termed as P1. The serum samples were collected to measure protein concentration. Total Protein Kit, Micro was used. Results: The mean age of the patients was 50.7±12.88 years old. Only 8% had a positive CRC family history. Rectosigmoid cancer represented the most frequent site, figured in 41% of the cases, followed by rectum cancer. Multiple sites of CRC metastasis were recorded in 15% of the patients. All patients received chemoradiation. Folinic acid (leucovorin), 5-FU, and oxaliplatin (FOLFOX) was the most used regimen, administered in 40% of the patients. Oxaliplatin and capecitabine (also called Xeloda) (XELOX) were administered in 14% of the patients. Folinic acid (leucovorin), 5-FU, oxaliplatin, and irinotecan (FOLFOXIRI) were administered in 16% of the patients. Single-agent oxaliplatin or carboplatin were administered in 6% of the patients, each. 5-FU plus leucovorin was administered to 12% of the patients. Three patients received irinotecan, and oxaliplatin (IROX). One patient received folinic acid (leucovorin), 5-FU and irinotecan (FOLFIRI). Also, Gemzar was administered to two patients only. A total of 80% of the patients underwent several surgical procedures. Anterior perineal resection (APR) and total mesorectal excision (TME) were the most common two surgeries, performed in 20 and in 30% of the patients, respectively. In P0 status, 44% of the patients suffered from low protein levels, and 13% of the patients were within the normal level. These findings were statistically different (p=0.03). After CRC management (i.e., P1 status), 70% of the patients had protein deficiency. These results have strong significant differences (p=0.000). The mean of protein concentration declined gradually after management, from 8.82±0.9 μg/L to 6.210.78 μg/L, with a strong association between a reduction in proteins levels towards deficiency and surgical procedures and chemotherapy protocols (p=0.000). Conclusion: The incidence of CRC is increasing annually, and the chance of being diagnosed with this type of cancer has risen in recent years. In the present study, the male to female ratio was 1:1.5, and the 5th decade of life was themost common age for the diagnosis of CRC. A negative family history and bowel inflammatory diseases (IBD) history did not exclude people from exposure to the incidence of CRC. Colorectal cancer with localized and moderately differentiated adenocarcinoma were the most common types in the present work. Tumor distance from the anal verge seems to be very important and plays a significant role in the choosing of surgical intervention types and chemoradiation protocols. Colorectal cancer acts as a complex condition and, in addition to its management, nutritional state influences it in different mechanisms. Most patients suffered from hypoproteinemia after surgery and chemoradiation. As a result, alteration in the treatment outcomes, delaying in wound healing, and an increase in postoperative complications may occur. (AU)

Evaluation of survival of patients with locally advanced head and neck cancer treated in a single center / Avaliação da sobrevida de pacientes com câncer de cabeça e pescoço localmente avançado tratados em um único centro

Abstract Introduction: Even with improved treatment outcomes with multimodality approaches, the question of what is the best initial treatment for locally advanced head and neck cancer still remains unanswered. Objective: To review the overall survival of a large cohort of head and neck cancer, patients with locally advanced head and neck cancer treated in a single institution. Material and methods: We studied a cohort of patients with locally advanced head and neck cancer treated in our institution in the last fifteen years. To gather a large sample of patients with adequate follow-up time, a cross-check between ours and Fundação Oncocentro de São Paulo databases were done. We included patients with head and neck cancer, clinical or pathological staging III or IV, treated with surgery followed by radiotherapy or surgery plus chemoradiation or radiotherapy alone or chemoradiation alone. Results: 796 patients with locally advanced head and neck cancer were included, 88% male, 44% age >60 years and 76% stage IV. The tumor location was the oral cavity (34%), oropharynx (27%), hypopharynx (17%) and larynx (17%). The treatment groups were chemoradiation alone (39.7%), surgery plus chemoradiation (26.3%), surgery followed by radiotherapy (18.5%) and radiotherapy alone (15.5%). Comparing the clinical variables between the treatment groups significant differences in age and clinical stage were observed. With a median follow up of 7.5 years (1-16 years), for the entire cohort, the overall survival at 5 and 10 years was 34.8% and 28%. The overall survival at 5 and 10 years was 16.7% and 12.2% for radiotherapy alone, 38.8% and 26.3% for surgery followed by radiotherapy, 28% and 16.6% for chemoradiation alone, and 37.3% and 23.2% for surgery plus chemoradiation. The staging IV (p = 0.03) and radiotherapy alone (p = 0.05), had a worst survival in multivariate analysis. Surgical groups vs. chemoradiation alone had no significant difference for overall survival. Conclusion: The present study is the largest cohort of locally advanced head and neck cancer of Brazilian patients to evaluate treatment outcomes. Although there were significant clinical differences between surgical and radiotherapy groups, surgery or chemoradiation alone as the initial treatment resulted in no significant difference in survival.

Resumo Introdução: Mesmo com a melhora dos desfechos de tratamento com abordagens multimodais, a dúvida sobre qual seria o melhor tratamento inicial para o câncer de cabeça e pescoço localmente avançado ainda permanece sem resposta. Objetivo: Mostrar a sobrevida global de uma grande coorte de pacientes com câncer de cabeça e pescoço localmente avançado tratados em uma única instituição. Material e método: Projetamos uma coorte de pacientes com câncer de cabeça e pescoço localmente avançado tratados em nossa instituição nos últimos 15 anos. Para reunir uma grande amostra de pacientes com tempo de seguimento adequado, foi realizada uma verificação cruzada entre nosso banco de dados e o banco de dados da fundação oncocentro de São Paulo. Foram incluídos os pacientes com câncer de cabeça e pescoço, estadiamento clínico ou histopatológico III ou IV, tratados com cirurgia seguida de radioterapia ou quimiorradioterapia ou radioterapia isolada ou quimiorradioterapia isolada. Resultados: Foram incluídos 796 pacientes com câncer de cabeça e pescoço localmente avançado, sendo 88% do sexo masculino, 44% com idade > 60 anos e 76% no estágio IV. O tumor estava localizado na cavidade oral (34%), orofaringe (27%), hipofaringe (17%) e laringe (17%). Os grupos de tratamento foram quimiorradioterapia (39,7%), cirurgia seguida de radioterapia ou quimiorradioterapia (26,3%), cirurgia seguida de radioterapia (18,5%) e radioterapia isolada (15,5%). Comparando as variáveis clínicas entre os grupos de tratamento, foram observadas diferenças significativas de idade e estágio clínico. Com uma mediana de tempo de seguimento de 7,5 anos (1-16 anos) para toda a coorte, a sobrevida global em 5 e 10 anos foi de 34,8% e 28%. A sobrevida global em 5 e 10 anos foi de 16,7% e 12,2% para radioterapia isolada, 38,8% e 26,3% para cirurgia seguida de radioterapia, 28% e 16,6% para quimiorradioterapia e 37,3% e 23,2% para cirurgia seguida de radioterapia ou quimiorradioterapia. O estágio IV (p = 0,03) e a radioterapia isolada (p = 0,05) apresentaram pior sobrevida na análise multivariada. Grupos cirúrgicos versus quimiorradioterapia não apresentaram diferença significante para a sobrevida global. Conclusão: O presente estudo é a maior coorte de câncer de cabeça e pescoço localmente avançado de pacientes brasileiros para avaliação dos desfechos do tratamento. Embora houvesse diferenças clínicas significativas entre os grupos cirúrgico e radioterápico, a cirurgia ou a quimiorradioterapia, como tratamento inicial, não apresentaram diferenças significantes em relação à sobrevida.

High serum superoxide dismutase activity improves radiation-related quality of life in patients with esophageal squamous cell carcinoma

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. Intensity-modulated radiation therapy and volume-modulated arc therapy have become the main treatments for esophageal carcinoma; however, side effects caused by radiotherapy greatly impact the quality of life in these patients. This study aimed to explore the impact of serum superoxide dismutase (SOD) levels on the prognosis of patients with ESCC undergoing radiotherapy. METHODS: Patients aged between 18 and 80 years with lower-middle ESCC who underwent radiotherapy were eligible for this assessment. Adverse events, responses, treatment outcomes, and overall survival (OS) were assessed. Between 2012 and 2014, 195 patients were enrolled, of which 65 were assigned to the low- and high-SOD groups based on their serum SOD values. RESULTS: The baseline characteristics were similar between the two groups, except for the T staging. Adverse events in the low-SOD group were significantly higher than those in the high-SOD group (radiation esophagitis, p=0.007; radiation pneumonitis, p=0.032; leukopenia, p=0.023; thrombocytopenia, p=0.037; anemia, p=0.041). There were no significant differences in response, treatment outcomes, or OS. CONCLUSION: In conclusion, high serum SOD activity improved post-radiotherapy quality of life but did not impact the prognosis of patients with ESCC. To the best of our knowledge, this study is the first to report that serum SOD activity is associated with radiation-induced toxicity and moderately increased radiotherapeutic response in patients with ESCC undergoing radiotherapy.

Identificação e correlação molecular e dinâmica de proteínas relacionadas à resistência ao tratamento neoadjuvante em células tumorais circulantes de pacientes com câncer de reto localmente avançado / Molecular and dynamic evaluation of proteins related to resistance to neoadjuvant treatment with chemoradiotherapy in circulating tumor cells of patients with locally advanced rectal cancer

INTRODUÇÃO: A quimiorradioterapia neoadjuvante (QRTN) consolidou-se como a principal estratégia para o tratamento do câncer de reto localmente avançado (CRLA). No entanto, respostas heterogêneas são observadas com o tratamento neoadjuvante, com apenas 15-20% dos pacientes com resposta patológica completa (RPC). Diante da necessidade de estratificar os pacientes em respondedores e não respondedores à QRTN antes do seu início, com o objetivo de aprimorar a seleção daqueles com maior probabilidade de obter uma RPC, vários estudos avaliam a identificação de possíveis biomarcadores. O objetivo primário deste estudo prospectivo foi analisar se a ausência da expressão do homólogo B de RAD23 (RAD23B) e da timidilato sintase (TYMS) nas células tumorais circulantes (CTCs) se correlacionaria com a RPC para os pacientes submetidos à QRTN e, assim, identificar possíveis respondedores ao tratamento. Os desfechos secundários foram avaliar a cinética das CTCs antes (C1) e após QRTN (C2), além da correlação da expressão de marcadores de resposta imune, como o Tumor Growth Factor ß Receptor I (TGF-ßRI) e Programmed Death ligand-1 (PD-L1) com a sobrevida livre de doença (SLD) e sobrevida global (SG). MÉTODOS: Entre 2016 e 2020, 63 pacientes com CRLA (cT3/T4 e/ou N+) submetidos a QRTN foram incluídos no estudo. As CTCs foram isoladas por ISET e avaliadas por imunocitoquímica. A expressão de RAD23B, TYMS, PD-L1 e TGF-ßRI foi avaliada nesta ordem de prioridade de acordo com o objetivo primário do estudo em cada momento de coleta e a disponibilidade de células (contagem de CTCs > 0) na amostra. RESULTADOS: Em C1, RAD23B foi detectado em 54,1% dos pacientes sem RPC e sua ausência em 91,7% dos pacientes com RPC (p = 0,014); Na segunda coleta, dos 13 pacientes com RPC, 10 não apresentaram expressão de RAD23B nas CTCs. Para os pacientes que não obtiveram RPC com QRTN, 51,7% apresentavam a expressão de RAD23B em CTC em C2 (p = 0,06). Na análise univariada (OR =0,077;IC 95%, 0,009-0,661; p = 0,019) e multivariada (OR= 0,064;CI 95%, 0,006-0,75; p = 0,029) para RPC, observamos que a expressão de RAD23B foi associado com menor chance de resposta em comparação com os pacientes com a ausência da expressão do RAD23B na C1. A ausência da expressão da TYMS foi observado em 90% dos pacientes com RPC e sua expressão em 51,7% sem RPC (p = 0,057). Na avaliação da cinética da CTCs pacientes com CTC2> CTC1 (cinética desfavorável) tiveram pior SLD (p = 0,00025) e SG (p = 0,0036) em comparação com aqueles com CTC2 ≤CTC1 (cinética favorável). A expressão de TGF-ßRI em qualquer momento das coletas correlacionou-se com pior SLD (p = 0,059). CONCLUSÃO: Demonstramos uma possível correlação entre a ausência de expressão de RAD23B e TYMS nas CTCs com a RPC, sendo um resultado importante para identificar os respondedores ao tratamento neoadjuvante, ajudando individualizar a abordagem terapêutica. Além disso, a cinética desfavorável e a expressão de TGF-ßRI nas CTCs se correlacionaram com pior sobrevida

INTRODUCTION: Neoadjuvant chemoradiotherapy (NCRT) has established itself as the main strategy for the treatment of locally advanced rectal cancer (LARC). However, heterogeneous responses are observed with neoadjuvant treatment, with only 15-20% of patients with complete pathological response (pCR). Given the need to stratify patients into responders and non-responders to NCRT prior to its initiation, in order to improve the selection of those most likely to obtain a pCR, several studies have assessed the identification of potential biomarkers capable of stratifying and monitoring the patient's response. The primary objective of this prospective study was to analyze whether the absence of RAD23 homolog B expression (RAD23B) and thymidylate synthase (TYMS) in circulating tumor cells (CTCs) would correlate with pCR for patients undergoing NCRT and thus identify possible responders to treatment. The secondary outcomes were to evaluate the kinetics of CTCs before (C1) and after NCRT (C2), in addition to the correlation of the expression of immune response markers, such as Tumor Growth Factor ß Receptor I (TGF-ßRI) and Programmed Death ligand- 1 (PD-L1) with clinical outcomes such as disease-free survival (DFS) and overall survival (OS). METHODS: Between 2016 and 2020, 63 patients (pts) with LARC (cT3 / T4 or N +) submitted to NCRT were included in the study. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). The expression of RAD23B, TYMS, PD-L1 and TGF-ßRI was evaluated in this order of priority according to the primary objective of the study at each time of collection (C1, C2 and C3) and the availability of cells (CTC count> 0) in the sample. RESULTS: In C1, RAD23B was detected in 54.1% of patients without pCR and its absence in 91.7% of patients with pCR (p = 0.014). In the second collection, of the 13 patients with pCR, 10 did not show RAD23B expression in the CTCs. For patients who did not obtain pCR with NCRT, 51.7% had RAD23B expression in CTC in C2 (p = 0.06). In the univariate (OR = 0.077; 95% CI, 0.009-0.661; p = 0.019) and multivariate (OR = 0.064; 95% CI, 0.006-0.75; p = 0.029) logistic regression models for pCR, we observed that the expression of RAD23B was associated with a lower chance of response compared to patients with the absence of RAD23B expression in C1. The absence of TYMS expression was observed in 90% of patients with pCR and its expression in 51.7% without pCR (p = 0.057). In the evaluation of CTCs kinetics patients with CTC2> CTC1 (unfavorable kinetics) had worse DFS (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤CTC1 (favorable kinetics). TGF-ßRI expression at any time of the collections was correlated with worse DFS (p = 0.059). CONCLUSION: We demonstrated a possible correlation between the absence of RAD23B and TYMS expression in CTCs with pCR, being an important result to identify respondents to neoadjuvant treatment, helping to individualize the therapeutic approach. In addition, the unfavorable kinetics and expression of TGF-ßRI in CTCs correlated with worse survival.

Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma / 中华医学杂志(英文版)

BACKGROUND@#The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC.@*METHODS@#We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS).@*RESULTS@#The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019).@*CONCLUSIONS@#CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

Outcomes of oesophageal cancer treated with neoadjuvant compared with definitive chemoradiotherapy

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.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Predictive value of magnetic resonance imaging characteristics before and after radiotherapy for the occurrence of severe radiation-induced late rectal injury in patients with rectal cancer / 中华胃肠外科杂志

Objective: Severe radiation-induced late rectal injury (sRLRI) directly affects the quality of life of patients with rectal cancer. Effective prediction of sRLRI before surgery may provide important information for the selection of surgical strategies and perioperative managements. The purpose of this study is to evaluate the feasibility of predicting sRLRI based on magnetic resonance imaging (MRI) features before and after radiotherapy for rectal cancer. Methods: This was a diagnostic study. Clinical and imaging data of 90 patients with rectal cancer receiving long-term radiotherapy from June 2013 to July 2018 in the Sixth Affiliated Hospital of Sun Yat-sen University were collected retrospectively. Case inclusion criteria: (1) rectal cancer was diagnosed by pathology and age of ≥ 18 years old; (2) patients received neoadjuvant chemoradiotherapy and anterior rectal resection; (3) follow up time ≥ 3 years; (4) patients had no history of other neoplasm. Exclusion criteria: (1) patients did not receive MRI examination in our hospital within 2 weeks before and/or 8 weeks after radiotherapy; (2) images were not good enough for evaluation; (3) medical records were incomplete; (4) patients had severe gastrointestinal diseases. According to the RTOG/EORTC classification criteria for radiation reactions, severe complications of grade 3-4 requiring surgical management were defined as sRLRI. T2WI and DWI images before and after radiotherapy were evaluated. The rectal wall thickness, bladder wall thickness, rectal sacral spacing and apparent diffusion coefficient (ADC) were measured. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above indicators for sRLRI. Results: Among the 90 patients with rectal cancer, 34 (37.8%) developed sRLRI. Before radiotherapy, the median rectal wall thickness of sRLRI and non-sRLRI patients was 4.530 mm and 4.355 mm, respectively; the median bladder wall thickness was 3.962 mm and 3.868 mm, respectively; the median rectal sacral spacing was 15.557 mm and 12.433 mm, respectively; the median ADC value of rectal wall was 1.620 ×10(-3) mm(2)/s and 1.653 ×10(-3) mm(2)/s, respectively. There were no significant differences in above indicators between sRLRI and non-sRLRI patients (all P>0.05). After radiotherapy, compared with non-sRLRI patients, sRLRI patients had increased rectal wall thickness (median: 8.239 mm vs. 6.223 mm, Z=-3.512, P=0.001), rectal sacral spacing (median: 17.728 mm vs. 13.885 mm, Z=-2.247, P=0.025), and change of rectal wall thickness after radiotherapy (median: 98.106% vs. 49.584%, Z=-4.169, P<0.001). After radiotherapy, there were no significant differences in the bladder wall thickness and its change value, the ADC value of rectal wall and its change rate before and after radiotherapy between the two groups (all P>0.05). The area under the curve (AUC) of the change rates of rectal wall thickness after radiotherapy, rectal wall thickness and rectal sacral spacing after radiotherapy for predicting sRLRI was 0.763, 0.722 and 0.642, respectively, while the sensitivity was 85.3%, 70.6% and 76.5%, respectively, and the specificity was 64.3%, 71.4% and 57.1%, respectively. Conclusion: Based on MRI examinations, assessments of rectal wall thickness after radiotherapy, the change rate of rectal wall thickness after radiotherapy, and rectal sacral spacing after radiotherapy are helpful for evaluating the risk of sRLRI after radiotherapy for patients with rectal cancer.

Effects of radical radiotherapy combined with different regimens of chemotherapy on radiation intestinal injury in patients with non-metastatic anal squamous cell carcinoma / 中华胃肠外科杂志

Objective: To investigate the effects of radical radiotherapy combined with different chemotherapy regimens (fluorouracil-based versus docetaxel plus cisplatin) on the incidence of radiation intestinal injury and the prognosis in patients with non-metastatic anal squamous cell carcinoma. Methods: A retrospective cohort study was conducted to recruit non-metastatic anal squamous cell carcinoma patients who underwent chemoradiotherapy in the Sixth Affiliated Hospital of Sun Yat-sen University and Nanfang Hospital from July 2013 to January 2021. Inclusion criteria: (1) newly diagnosed anal and perianal squamous cell carcinoma; (2) completed radical radiotherapy combined with concurrent chemotherapy; (3) tumor could be evaluated before radiotherapy. Exclusion criteria: (1) no imaging evaluation before treatment, or the tumor stage could not be determined; (2) patients undergoing local or radical resection before radiotherapy; (3) distant metastasis occurred before or during treatment; (4) recurrent anal squamous cell carcinoma. A total of 55 patients (48 from the Sixth Affiliated Hospital of Sun Yat-sen University and 7 from Nanfang Hospital) were given fluorouracil (the 5-FU group, n=34) or docetaxel combined with the cisplatin (the TP group, n=21). The evaluation of radiation intestinal injury, hematological toxicity and 3-year disease-free survival (DFS) rate were compared between the two groups. The effects of chemotherapy regimen and other clinicopathological factors on the incidence and severity of acute and chronic radiation intestinal injury were analyzed. The assessment of radiation intestinal injury was based on the American Cancer Radiotherapy Cooperation Group (RTOG) criteria. Results: During radiotherapy and within 3 months after radiotherapy, a total of 45 patients developed acute radiation intestinal injury, including 18 cases of grade 1 (32.7%), 22 cases of grade 2 (40.0%) and 5 cases of grade 3 (9.1%). No patient developed chronic radiation intestinal injury. Among the 34 patients in the 5-FU group, 21 had grade 2-3 radiation intestinal injury (21/34, 61.8%), which was significantly higher than that in the TP group (6/21, 28.6%) (χ(2)=5.723, P=0.017). Multivariate analysis showed that 5-FU chemotherapy regimen was an independent risk factor for radiation intestinal injury (HR=4.038, 95% CI: 1.250-13.045, P=0.020). With a median follow-up period of 26 (5-94) months, the 3-year DFS rate of patients in TP group and 5-FU group was 66.8% and 77.9%, respectively, whose difference was not significant (P=0.478). Univariate analysis showed that the DFS rate was associated with sex, age, tumor location, T stage, N stage, and induction chemotherapy (all P<0.05), while the DFS rate was not associated with chemotherapy regimen or radiation intestinal injury (both P>0.05). Multivariate analysis revealed that age ≥ 50 years old was an independent risk factor affecting the prognosis of patients (HR=8.301, 95% CI: 1.130-60.996, P=0.038). Conclusions: For patients with non-metastatic anal squamous cell carcinoma, radical radiotherapy combined with TP chemotherapy regimen can significantly reduce the incidence of radiation intestinal injury as compared to 5-FU regimen. However, due to the short follow-up time, the effect of different chemotherapy regimens on the prognosis is not yet clear.

Research progress and challenges of neoadjuvant therapy for esophageal squamous cell carcinoma / 中华胃肠外科杂志

Surgery is the main treatment for resectable esophageal squamous cell carcinoma. However, for patients with locally advanced lesions, surgery-based comprehensive treatment is the best treatment strategy. According to the results of some randomized controlled clinical studies and meta-analysis, preoperative neoadjuvant therapy is recommended to improve the survival rate of patients. Neoadjuvant therapy includes neoadjuvant chemotherapy, chemoradiotherapy, targeted therapy and immunotherapy. Great progress has been made in neoadjuvant therapy, but there are still many clinical problems that need to be solved urgently, including the efficacy and safety of neoadjuvant therapy, the choice of neoadjuvant regimen and treatment cycle, the best combination and advantages of multimodal treatment, and the selection of responders to treatment, etc. This article provides a systematic review of the latest developments and existing controversies in neoadjuvant therapy for esophageal squamous cell carcinoma.

Clinical features and prognosis of anastomotic leak after anterior resection for rectal cancer following neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

Objective: To explore clinical features and prognosis of anastomotic leak (AL) after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients. Methods: A retrospective cohort study was performed. Data were retrieved from colorectal cancer database of the Sixth Affiliated Hospital, Sun Yat-sen University. The clinical data of 470 patients with rectal cancer who underwent anterior resection after neoadjuvant chemoradiotherapy at our department from September 2010 to December 2018 were enrolled. Clinical features and outcome of postoperative AL were analyzed. The primary outcomes were the short-term and long-term incidence and severity of AL (ISREC grading standard was adopted). The secondary outcomes were the prognostic indicators of AL, including the secondary chronic presacral sinus, anastomotic stenosis and persistent stoma. Patients received regular follow-up every 3-6 months after surgery, including physical examination, blood test, colonoscopy and image; those received follow-up once a year after postoperative 2-year; those who did not return to our hospital received telephone follow-up. Data of this study were retrieved up to January 2020. Univariate χ(2) test and multivariate logistic analysis were used to identify risk factors of AL and prognostic factors of persistent stoma. Results: There were 331 males (70.4%) with the average age of (53.5±11.6) years. Distance from tumor to anal verge ≤ 5 cm was found in 228 (48.5%) patients. The diverting stoma was performed in 440 (93.6%) patients. After a median follow-up of 28 months, AL was found in 129 (27.4%) patients, including 67 (14.3%) patients with clinical leak (ISREC grade B-C). The median time for diagnosis of AL was 70 days (2-515 days) after index surgery. Common symptoms included sacrococcygeal pain (27.9%, 36/129), purulent discharge through anus (25.6%, 33/129), and rectal irritation (17.8%, 23/129). Sixty five point one percent (84/129) of the defect site was at the posterior wall of the anastomosis. Transanal incision and drainage or lavage (27.9%, 36/129) and percutaneous drainage under ultrasound or CT (17.1%, 22/129) were the most common management. Chronic presacral sinus tract could not be evaluated in 12 patients because imaging was performed more than 1 year after the operation. Evaluation beyond 1 year showed that 73 of 458 eligible patients (15.9%) were found with chronic presacral sinus, accounting for 62.4% (73/117) of patients with AL; 69 of 454 (15.2%) were diagnosed with anastomotic stenosis, of whom 49 were secondary to AL; 59 of 470 (12.6%) had persistent stoma due to AL. Univariate analysis showed that male, operative duration > 180 minutes, intraoperative blood loss >150 ml, and pelvic radiation injury were associated with AL (all P<0.05). Multivariate analysis showed that male (OR=1.72, 95% CI: 1.04-2.86, P=0.036), intraoperative blood loss > 150 ml (OR=1.82, 95% CI: 1.11-2.97, P=0.017), and pelvic radiation injury (OR=4.90, 95% CI: 3.09-7.76, P<0.001) were independent risk factors of AL after anterior resection. For patients with AL, clinical leak (ISREC grade B-C) (OR=9.59, 95% CI: 3.73-24.69, P<0.001), age ≤55 years (OR=3.35, 95% CI: 1.35-8.30, P=0.009), distance from tumor to anal verge ≤ 5 cm (OR=3.33, 95% CI: 1.25-8.92, P=0.017), and pelvic radiation injury (OR=3.29, 95% CI: 1.33-8.14, P=0.010) were independent risk factors of persistent stoma. Conclusions: AL after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients is common. Among patients with AL, the proportion of those needing persistent stoma is high. Pelvic radiation injury is significantly associated with occurrence of AL and subsequent persistent stoma. Sphincter-preserving surgery for rectal cancer should be selectively used based on the risk of pelvic radiation injury, which is beneficial to reduce the incidence of AL and improve the quality of life.

Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.

Prognosis and complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

Objective: To investigate the prognosis and postoperative complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A descriptive case series study was carried out. Patient inclusion criteria: (1) patients who underwent local excision by transanal endoscopic microsurgery (TEM) after nCRT; (2) magnetic resonance evaluated tumor regression grade (mrTRG) as 1, 2 after nCRT;(3) American Society of Anesthesiologists class I to III. Patient exclusion criteria: (1) with multiple primary colorectal cancers; (2) with other malignant tumors within five years; (3) with emergency surgicery indications like digestive tract obstruction, perforation or bleeding. Clinicopathological and follow-up data of rectal cancer patients with obvious tumor regression after nCRT who underwent local excision in Peking Union Medical College Hospital from January 2010 to August 2019 were retrospectively collected. Outcome measures included disease-free survival (DFS), short-term postoperative complications, and at postoperative 1-year during follow up, gas continence, fecal continence, and quality of life (using the EORTC QLQ-CR29 scale, higher score indicated worse quality of life) at postoperative 1-year. Results: A total of 40 patients were included in this study. There were 27 males and 13 females with an average age of (66.7±12.3) years. Preoperative rectal ultrasound and other imaging examinations indicated that the tumor was located in the anterior wall in 16 cases, the lateral wall in 12 cases, and the posterior wall in 12 cases. The distance between the lower margin of the tumor and the anal verge was (4.3±1.2) cm before nCRT and (5.1±0.9) cm after nCRT. According to mrTRG, 31 cases were assessed as mrTRG 1 and 9 cases as mrTRG 2. All the patients received local extended excision of rectal cancer using TEM platform. A total of 19 cases(47.5%) suffered from complications within one month postoperatively. Clavien-Dindo grade I complications happened in 14 cases, grade II in 3 patients, and grade III in 2 cases, who all were healed by conservative treatment. Except that 2 patient presented severe low anterior resection syndrome (LARS) at 1 year postoperatively, no severe anal dysfunction was found in this cohort patients. EORTC QLQ CR29 scale results for quality of life showed that at 1 year after TEM excision, except taste (Z=-1.968, P=0.049), anxiety (Z=-3.624, P<0.001) and skin irritation (Z=-2.420, P=0.023) were worse than the situation before neoadjuvant therapy, there were no statistically significant differences in other assessment results between pre-operation and post-operation (all P>0.05). Postoperative pathological results indicated complete tumor regression (pTRG0) in 17 cases, moderate remission (pTRG1) in 13, and mild remission (pTRG2) in 10. During the follow-up of (49.1±29.6) months, 3 patients had local recurrence and 4 had distant metastasis (3 patients with liver metastasis and 1 patient with lung metastasis followed by liver metastasis). No death was found and the 5-year disease-free survival (DFS) was 84.3%. Conclusions: Local excision through TEM following nCRT not only can be adopted as an important means to accurately determine complete clinical remission (cCR), but also has high therapeutic value for rectal cancer patients presenting cCR or near cCR, with little impact on defecatory function and quality of life. However, the morbidity of complication of TEM excision after nCRT is relatively high and there is a risk of recurrence and metastasis. Therefore, it is still necessary to strictly select the indications of local excision.

Pros and cons of perioperative therapy in the protection of organ function in rectal cancer / 中华胃肠外科杂志

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.

Prehabilitation for gastrointestinal cancer patients / 中华胃肠外科杂志

Gastrointestinal cancer and related treatments (surgery and chemoradiotherapy) are associated with declined functional status (FS) that has impact on quality of life, clinical outcome and continuum of care. Psychological distress drives an impressive burden of physiological and psychiatric conditions in oncologic care. Cancer patients often experience anxiety, depression, low self-esteem and fears of recurrence and death. Cancer prehabilitation is a process from cancer diagnosis to the beginning of treatment, which includes psychological, physical and nutritional assessments for a baseline functional level, identification of comorbidity, and targeted interventions that improve patient's health and functional capacity to reduce the incidence and the severity of current and future impairments with cancer, chemoradiotherapy and surgery. Multimodal prehabilitation program encompasses a series of planned, structured, repeatable and purposive interventions including comprehensive physical exercise, nutritional therapy, and relieving anxiety and depression, which integrates into best perioperative management ERAS pathway and aims at using the preoperative period to prevent or attenuate the surgery-related functional decline, to cope with surgical stress and to improve the consequences. However, a number of questions remain in regards to prehabilitation in gastrointestinal cancer surgery, which consists of the optimal makeup of training programs, the timing and approach of the intervention, how to improve compliance, how to measure functional capacity, and how to make cost-effective analysis. Therefore, more high-level evidence-based studies are expected to evaluate the value of implementation of prehabilitation into standard practice.

Current status and prospect of perioperative therapy for locally advanced gastric cancer / 中华胃肠外科杂志

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.

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis / 中华医学杂志(英文版)

BACKGROUND@#Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy (NCRT). This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis.@*METHODS@#In total, 1296 patients with NCRT or post-operative chemoradiotherapy (PCRT) were enrolled in this study between January 2008 and December 2015. Propensity score matching was used to correct for differences in baseline characteristics between the two groups. After propensity score matching, the metastasis pattern, including metastasis sites and timing, was compared and analyzed.@*RESULTS@#After propensity score matching, there were 408 patients in the PCRT group and 245 patients in the NCRT group. NCRT significantly reduced local recurrence (4.1% vs. 10.3%, P = 0.004), but not distant metastases (28.2% vs. 27.9%, P = 0.924) compared with PCRT. In both the NCRT and PCRT groups, the most common metastasis site was the lung, followed by the liver. The NCRT group developed local recurrence and distant metastases later than the PCRT group (median time: 29.2 [18.8, 52.0] months vs. 18.7 [13.3, 30.0] months, Z = -2.342, P = 0.019; and 21.2 [12.2, 33.8] vs. 16.4 [9.3, 27.9] months, Z = -1.765, P = 0.035, respectively). The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group (39/114, 34.2%) and NCRT group (21/69, 30.4%). However, 20.3% (14/69) of the distant metastases appeared in the 3rd year in the NCRT group, while this number was only 13.2% (15/114) in the PCRT group.@*CONCLUSIONS@#The predominant site of distant metastases was the lung, followed by the liver, for both the NCRT group and PCRT group. NCRT did not influence the predominant site of distant metastases, but the NCRT group developed local recurrence and distant metastases later than the PCRT group. The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.