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Efficacy Analysis of Combining Sintilimab with Neoadjuvant Chemotherapy in Treating Middle and Advanced Rectal Cancer Based on Big Data

Efficacy Analysis of Combining Sintilimab with Neoadjuvant Chemotherapy in Treating Middle and... Hindawi Journal of Oncology Volume 2022, Article ID 8675587, 7 pages https://doi.org/10.1155/2022/8675587 Research Article Efficacy Analysis of Combining Sintilimab with Neoadjuvant Chemotherapy in Treating Middle and Advanced Rectal Cancer Based on Big Data 1 1 1 1 2 1 Yifei Wang, Jiandong Fei, Yanan Zheng, Ping Li, Xiaodong Ren, and Yongzhu An Department of Gastrointestinal Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000 Hebei, China Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000 Hebei, China Correspondence should be addressed to Yongzhu An; anyongzhu@hbbfyfy.com.cn Received 27 June 2022; Revised 9 August 2022; Accepted 25 August 2022; Published 16 September 2022 Academic Editor: Alamgeer Yuchi Copyright © 2022 Yifei Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To analyze the efficacy of combining sintilimab with neoadjuvant chemotherapy in treating middle and advanced rectal cancer based on big data. Methods. According to the inclusion and exclusion criteria, 43 patients with middle and advanced rectal cancer, who were treated with sintilimab and neoadjuvant chemotherapy in General Surgery of the hospitals of Zhangjiakou city from January 2020 to January 2022, were selected for the retrospective study. The patients’ short-term efficacy was scientifically evaluated, and the factors affecting efficacy and the correlation were analyzed. Results. Among the 43 enrolled patients, 30 of them had regional lymphatic metastasis but none had distant metastasis; most patients were at Broders II and TNM III, and all of them had adenocarcinoma; the total response rate was 69.77% (30 cases), with no grade IV and V adverse reactions; the patients were divided into the effective group and the ineffective group after treatment based on the evaluation results of short- term efficacy, and analysis of the relevant factors exposed in both groups revealed significant differences in age, tumor size, CEA, NLR value, PLR value, TNM stage, and presence of combined lymphatic metastasis between the two groups (P <0:05); univariate analysis showed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were the independent risk factors affecting the efficacy in patients with middle to advanced rectal cancer (P <0:05); and through the Spearman correlation analysis of the above independent risk factors, it was further confirmed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were negatively correlative with the efficacy of combining sintilimab with neoadjuvant chemotherapy in treating middle to advanced rectal cancer (P <0:05). Conclusion. Combining sintilimab with neoadjuvant chemotherapy has good efficacy and safety profile, which is conducive to subsequent surgery; in contrast, larger tumor diameter, higher CEA level, higher TNM stage, and more serious lymphatic metastasis are all independent risk factors affecting treatment sensitivity and can lead to poor efficacy. 1. Introduction tralia, and New Zealand and 392,000 new cases in China in 2018. Its early symptoms are not obvious, and the incidence is relatively high in men aged 40-80 years. At present, surgi- Rectal cancer is one of the most common malignant tumors of the digestive tract. According to the 2020 global epidemi- cal treatment is in the central position in rectal cancer treat- ment, because it provides patients at the early stage with ological statistics on cancer published by the International Agency for Research on Cancer (IARC), rectal cancer has long-term survival and those who can only receive limited treatment if they have local recurrence or distant metastasis become the 3rd most prevalent malignant tumor in men with better survival in combination with chemoradiotherapy and the 2nd in women worldwide, with the highest inci- dence in developed countries such as North America, Aus- [1]. For patients with locally advanced rectal cancer, 2 Journal of Oncology less than 3 months; (6) concurrent acute infection, such as neoadjuvant chemotherapy can lower the tumor stage, and some reports have confirmed that the application of neoad- lung infection and urinary system infection; (7) pregnant juvant chemotherapy before total mesorectal excision or lactating women; and (8) low compliance with treatment (TME) is the “gold standard” for the treatment of patients and lost to follow-up. with stage II and III rectal cancer [2, 3]. In addition, some 2.3. Patient Screening. According to the inclusion and exclu- published works and reports also state that neoadjuvant che- sion criteria, 43 patients with middle and advanced rectal motherapy has the potential to reduce local recurrence. In cancer, who were treated with sintilimab and neoadjuvant recent years, the studies of immune checkpoint inhibitors chemotherapy in General Surgery of the hospitals of Zhang- (ICIs) in various tumors are growing vigorously, and the jiakou city from January 2020 to January 2022, were selected results have shown that ICIs have good therapeutic effect. for the retrospective study; the study plan met the code of Immunotherapy is claimed to significantly improve the ethics and was reviewed and approved by the ethics commit- prognosis of colorectal cancer patients, and ICIs have also tees of the hospitals of Zhangjiakou city. been recommended as a first-line option for advanced rectal cancer [4–7]. Related studies suggest that ICIs show good 2.4. Methods effects in the neoadjuvant treatment of resectable rectal can- cer; meanwhile, ICI drugs also have a great potential in the 2.4.1. Sintilimab. Patients were treated with third-line and comprehensive treatment decision-making of locally above anti-PD-1 mAb monotherapy or in combination with advanced and early rectal cancer. In 2022, sindilizumab as other agents, the single dosage of sintilimab injection an innovative PD-1 inhibitor drug was successfully included (Tyvyt®) (specification: 100 mg; manufacturer: Innovent in the CSCO guidelines for the clinical use of ICIs, achieving Biologics (Suzhou) Co., Ltd.; NMPA approval no. the breakthrough that all first-line therapies for five major S20180016) was 200 mg, and it was administered once every tumors were included in the CSCO guidelines [8–10]. The 3 weeks until the downstaging effect and surgical resection use of immunotherapy in neoadjuvant treatment is mostly indicators were met, so as to improve the rate of radical dependent on the safety and efficacy of the treatment, and resection (R0 resection). it is still in the stage of active exploration from relevant data at home and abroad, with few clinical studies reported. 2.4.2. Neoadjuvant Chemotherapy. XELOX scheme: from Therefore, this article mainly collected middle and advanced day 1 to day 14, 1000 mg/m of capecitabine was given twice rectal cancer patients treated with sindilizumab plus neoad- daily; and at day 1, 130 mg/m of oxaliplatin was given. If a juvant chemotherapy in the General Surgery of the hospitals second course of chemotherapy was implemented, it should to carry out a retrospective study and to inquire about the be started at day 22 of radiotherapy. clinicopathological factors related to the treatment efficacy, avoiding ineffectiveness or overtreatment, which is also ben- 2.5. Observation Indicators. Clinical characteristics: the eficial to guide the preoperative treatment regimen and enrolled patients’ clinical information including age (with achieve the individualized treatment of middle and 55 years old as the critical value), gender, smoking, Broders advanced rectal cancer. classification, ECOG score, and TNM stage was recorded. Short-term efficacy: patients received reexamination after 4 weeks of treatment and were evaluated according to 2. Materials and Methods the WHO criteria for short-term objective response evalua- 2.1. Inclusion Criteria. (1) All patients were diagnosed with tion in solid tumors [11]. Complete disappearance of tumor middle and advanced rectal cancer after CT, MRI, and path- lesions and maintenance for ≥4 weeks were considered com- plete remission (CR); ≥30% reduction in volume of tumor ological examination; (2) the TNM stages of the patients were IIc and III; (3) the ECOG score was less than 3 points; lesions compared with that before treatment and mainte- (4) the patients had basically normal routine blood test nance for ≥4 weeks represented partial remission (PR); result, ECG, coagulation function, and liver and kidney <30% reduction in volume of tumor lesions compared with function; (5) the patients failed in first-line oxaliplatin+tar- that before treatment or <20% increase represented stable disease (SD); and ≥20% increase in volume of tumor lesions geted therapy chemotherapy and had not receive other PD-1 immunotherapy; (6) the patients did not have contra- compared with that before treatment or appearance of new indications of sindilizumab and chemotherapy; (7) the lesions represented progressive disease (PD), with total patients received TME after neoadjuvant chemotherapy; response = CR + PR. and (8) the patients and their family members understood Adverse reactions: according to the Common Terminol- ogy Criteria for Adverse Events (CTCAE) v4.0 of the the study and signed the treatment consent and study consent. National Cancer Institute (NCI) [12], the adverse reactions were divided into grades I to V (grade I: mild adverse reac- 2.2. Exclusion Criteria. Exclusion criteria are as follows: (1) tion, asymptomatic or mild symptoms, intervention not complicated with other malignant tumors; (2) complicated indicated; grade II: moderate adverse reactions, clinical with heart disease, severe hypertension, and other diseases symptoms that require intervention and may affect body of the cardiovascular system; (3) complicated with hemato- function, but daily life will not be affected; grade III: severe logical system diseases and severe internal medicine diseases; adverse reactions, complicated symptoms that require active (4) central nervous system metastases; (5) estimated survival intervention and treatment; grade IV: life-threatening Journal of Oncology 3 2.6. Statistical Processing. In this study, the data processing Table 1: Clinical characteristics of 43 patients (n =43). software was SPSS 22.0, which was mainly used to calculate Clinical data Number of cases Proportion (%) the between-group differences of data; the picture drawing Age software was GraphPad Prism 7 (GraphPad Software, San Diego, USA); the items included were enumeration data ≤55 years 20 46.51 and measurement data, which were expressed by ½nð%Þ >55 years 23 53.49 and (x ± s), examined by the X test and t-test, and met nor- Gender mal distribution; and differences were considered statisti- Male 28 65.12 cally significant when P <0:05. Female 15 34.88 Smoking 3. Results Yes 24 55.81 3.1. Clinical Characteristics. Among the 43 enrolled patients No 19 44.19 (aged 42 to 74 years) of the study, there were 28 males and Broders grade 15 females, 30 patients had regional lymphatic metastasis, I 4 9.30 and none had distant metastasis; most patients were at Bro- II 31 72.09 ders II and TMN III stage, all of them had adenocarcinoma. III 8 18.60 See Table 1 for statistical data. ECOG score 3.2. Short-Term Efficacy. All 43 patients finished sintilimab 0-1 point 26 60.47 treatment, neoadjuvant chemotherapy, and surgical treat- 2 points 17 39.53 ment and completed clinical efficacy evaluation. There were TNM stage 10 CR cases, 20 PR cases, 8 SD cases, and 5 PD cases and a IIc 13 30.23 total of 30 effective cases. See Figure 1. III 30 69.77 3.3. Adverse Reactions. After recording patients’ adverse reactions, it was found that patients did not have grade IV 69.77% and V adverse reactions, and the incidence rate of vomiting and nausea was the highest, followed by granulocytopenia and mucocutaneous damage. See Table 2. 46.51% 3.4. Analysis of Factors Related to Treatment Effectiveness. 23.26% The patients were divided into the effective group (n =30) 18.60% and the ineffective group (n =30) after treatment based on 11.63% the evaluation results of short-term efficacy, and analysis of the relevant factors exposed in both groups revealed signifi- CR PR SD PD Total efficac y cant differences in age, tumor size, CEA, NLR value, PLR value, TNM stage, and presence of combined lymphatic Figure 1: Evaluation results of patients’ short-term efficacy. metastasis between the two groups (P <0:05). See Table 3. 3.5. Logistic Regression Analysis. After including the single adverse reactions that may lead to disability and even organ factors into logistic regression analysis, it was showed that damage or dysfunction; grade V: death). tumor size, CEA, TNM stage, and lymphatic metastasis were Fasting venous blood was taken from all patients after independent risk factors affecting the efficacy of combining treatment and tested for white blood cell count (normal sintilimab with neoadjuvant chemotherapy in treating mid- range: 4:0 – 10:0×10 /L), neutrophils (normal range: 1:80 dle and advanced rectal cancer (P <0:05). See Table 4. 9 9 – 6:30 × 10 /L), lymphocytes (normal range: 0:8 – 4× 10 / L), platelets (normal range: 100 – 300 × 10 /L), CEA (normal 3.6. Correlation Analysis. After performing Spearman corre- range: 3.5–5.0 ng/mL), CA199 (normal range: <37 IU/mL), lation analysis of the above independent risk factors, it was NLR (normal range: 1–3), and PLR (normal range: 63.0– further confirmed that tumor size, CEA, TNM stage, and 182.6). combined lymphatic metastasis were negatively correlated The related factors, such as age (>55 years old), tumor with the efficacy of combining sintilimab with neoadjuvant size (≥3 cm), gender (male), distance between tumor and chemotherapy in treating middle and advanced rectal cancer anal verge (≥5 cm), concurrent chemotherapy cycle (≥3 (P <0:05). See Table 5. weeks), neoadjuvant chemotherapy cycle (≥2 weeks), white blood cell count, neutrophil, lymphocyte, platelet, CEA, 4. Discussion CA199, NLR value, PLR value, TNM stage, and lymph node metastasis, were included in the single variate analysis of In recent years, neoadjuvant chemoradiotherapy has gradu- treatment effectiveness, and then, logistic regression analysis ally walked into the popular field, and numerous previous and Spearman correlation analysis were performed. studies have shown that the comprehensive treatment mode (%) 4 Journal of Oncology Table 2: Evaluation results of patients’ adverse reactions. Adverse reactions Grade I Grade II Grade III Grade IV Grade V Total incidence rate½ n% ðÞ Nausea 17 2 0 0 0 19 (44.19) Vomiting 15 3 1 0 0 19 (44.19) Diarrhea 6 5 0 0 0 11 (25.58) Leukopenia 8 4 0 0 0 12 (27.91) Granulocytopenia 11 4 2 0 0 17 (39.53) Thrombocytopenia 3 3 0 0 0 6 (13.95) Mucocutaneous damage 10 4 1 0 0 15 (34.88) Neurotoxicity 9 2 0 0 0 11 (25.58) Peripheral phlebitis 4 1 0 0 0 5 (11.63) Table 3: Analysis of factors related to treatment effectiveness. Related factors Ineffective group (n =13)Effective group (n =30) X /t P Age (>55 years) 10 (72.92) 13 (43.33) 4.113 0.043 Gender (male) 7 (53.85) 21 (70.00) 1.042 0.307 Tumor size (≥3 cm) 8 (61.54) 8 (26.67) 4.721 0.030 Distance between tumor and anal verge (≥5 cm) 7 (53.85) 16 (53.33) 1.042 0.307 Concurrent chemotherapy cycle (≥3 weeks) 6 (46.15) 11 (36.67) 0.342 0.559 Neoadjuvant chemotherapy cycle (≥2 weeks) 8 (61.54) 16 (53.33) 0.248 0.619 3:82 ± 0:55 4:03 ± 0:68 White blood cell count (×10 /L) 0.981 0.332 Neutrophil (×10 /L) 3:04 ± 1:01 3:10 ± 1:04 0.175 0.862 0:90 ± 0:54 0:92 ± 0:49 Lymphocyte (×10 /L) 0.119 0.906 Platelet (×10 /L) 216:94 ± 60:16 218:33 ± 68:73 0.063 0.950 5:24 ± 1:48 2:64 ± 1:28 CEA (ng/mL) 5.836 <0.001 CA199 (IU/mL) 30:31 ± 12:16 23:85 ± 11:95 1.575 0.123 4:16 ± 0:62 3:61 ± 0:85 NLR value 2.098 0.042 PLR value 284:03 ± 13:85 270:11 ± 13:74 3.044 0.004 TNM stage 4.488 0.034 IIc 1 (7.69) 12 (40.00) III 12 (92.31) 18 (60.00) Lymphatic metastasis 12 (92.31) 18 (60.00) 4.488 0.034 Table 4: Multivariate logistic regression analysis. Variable B S.E. Wals df Sig. Exp (B) 95% C.I. of Exp (B) Tumor size -1.482 0.704 4.431 1 0.035 0.227 0.057-0.903 CEA (ng/mL) -1.240 0.376 10.904 1 0.001 3.457 1.656-7.218 TNM stage -2.079 1.106 3.538 1 0.006 0.125 0.014-1.091 Lymphatic metastasis -2.079 1.106 3.538 1 0.006 0.125 0.014-1.091 of neoadjuvant therapy combined with radical surgery has a chance of recurrence in some patients; in addition, it can relatively good effect on reducing the pathological stage of reduce the total number and positive rate of lymph nodes middle and advanced rectal cancer, lowering the rate of local in postoperative specimens, which is beneficial to the recurrence, prolonging survival time, and improving the rate improvement of the curative resection rate; and finally, neo- of anal conserving and the quality of life [13, 14]. Through adjuvant therapy reduces the tumor volume, increases the preoperative neoadjuvant chemoradiotherapy, it is able to distance between the lower edge of the tumor and the anal achieve postoperative pathological outcome as CR with low verge, and increases the success rate of anal-conserving Journal of Oncology 5 was not low but was within an acceptable range from the Table 5: Spearman correlation analysis. point of view of clinical treatment. The patients were divided Variable N Correlative coefficient Significance into the effective group and the ineffective group after treat- Tumor size 43 -0.331 0.030 ment based on the evaluation results of short-term efficacy, ∗∗ and analysis of the relevant factors exposed in both groups -0.664 CEA (ng/mL) 43 <0.001 revealed significant differences in age, tumor size, CEA, -0.323 TNM stage 43 0.035 NLR value, PLR value, TNM stage, and presence of com- -0.323 Lymphatic metastasis 43 0.035 bined lymphatic metastasis between the two groups (P <0:05); after including the single factors into logistic Note: ∗ indicated significant correlation at the 0.05 level (two-sided); ∗∗ indicated a significant correlation at the 0.01 level (two-sided). regression analysis, it was showed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were the surgery. Meanwhile, concomitant with the continuous devel- independent risk factors affecting the efficacy of combining opment of medical treatment, ICIs represented by anti-PD-1 sintilimab with neoadjuvant chemotherapy in treating mid- dle and advanced rectal cancer (P <0:05); and after per- mAb have become a research hotspot for cancer therapy, and a pan-tumor clinical trial study found that patients with forming Spearman correlation analysis of the above mismatch repair dysfunction and high microsatellite insta- independent risk factors, it was further confirmed that bility might benefit from anti-PD-1 mAb therapy, but there tumor size, CEA, TNM stage, and combined lymphatic is still insufficient evidence, and immunotherapy strategies metastasis were negatively correlative with the efficacy of combining sintilimab with neoadjuvant chemotherapy in for rectal cancer are under continuous exploration. The advent of sindilizumab marks the entry of antitumor immu- treating middle and advanced rectal cancer (P <0:05). In notherapy in China into the innovation era. It is character- terms of TNM studies in malignant tumors, reports have ized by high affinity, long-lasting, stability and high target confirmed that the later the T stage of the tumor, the poorer occupancy, and the objective response rate and disease con- the efficacy [19–21]. As the course of the disease progresses, the depth of tumor infiltration trol rate of immunotherapy using this drug for relapsed and increases, the blood supply is refractory Hodgkin lymphoma are as good as those of inno- relatively insufficient, and the tumor cells suffer from poor vative drugs of the international class [15, 16]. At present, nutrition and hypoxia, which reduce the treatment radiotherapy combined with immunotherapy is the research sensitivity. hotspot of tumor regression, and the systemic immune The sensitivity of mAb therapy and chemotherapy is response induced before surgery can make the body produce dependent not only on the biological characteristics of immune memory, while after surgery, patients cannot pro- the tumor itself but also on the microenvironment in duce immune-mediated sustained antitumor effects due to which it resides. In vivo studies have found that tumor tumor resection, so neoadjuvant chemotherapy combined cells dying after chemoradiotherapy are able to present with immunotherapy is also rational to a certain extent. tumor associated antigens to host immune cells, activating Based on this, the efficacy of combining sindilizumab with the body tumor response. Therefore, hematological indices neoadjuvant chemotherapy in treating middle and advanced can also be an influential factor in the evaluation of recur- rectal cancer was explored herein, and the related factors rence and prognosis. The results of available studies sug- affecting efficacy were analyzed based on data. gest that neutrophils, NLR, lymphocytes, platelets, and The evaluation of clinical results of 43 patients revealed CEA have some correlation with the efficacy and clinico- that there were 10 CR cases, 20 PR cases, 8 SD cases, and 5 pathological characteristics of neoadjuvant chemoradio- PD cases, and the overall response rate of treatment was therapy and are somewhat valuable in judging the 69.77% (30 cases), which was higher compared with the pre- prognosis [22, 23]. CEA is widely used to predict the effi- vious results. On the one hand, the study result affirmed the cacy of neoadjuvant chemoradiotherapy for rectal cancer, efficacy of sindilizumab combined with neoadjuvant chemo- with demonstrated efficacy predictive value. The changes therapy in patients with medium and advanced rectal can- in NLR and PLR, novel systemic immune response indica- cer; on the other hand, because sindilizumab injection was tors, are caused by the synergistic effect of neutrophils, officially marketed in mainland China only in 2019 and the platelets, and lymphocytes. Relevant studies have shown duration of its clinical use for rectal cancer treatment is rel- that preoperative NLR levels and tumor volume size in atively short, so there are relatively few clinical cases. In cancer patients have significant associations [24, 25]. In addition, based on the study criteria, most of the enrolled this study, in logistic regression analysis and correlation patients were TNM stage III patients, some of them had analysis, the difference of NLR and PLR was not found, regional lymph node metastasis, and none had distant so the reference and guidance value of their level changes metastasis, and therefore, the specificity of case screening for the treatment of rectal cancer with the combination of may have some influence on the overall efficacy statistics. sindilizumab and neoadjuvant chemotherapy should be Based on the statistics of adverse reactions in patients, no confirmed with large-sample and multicenter studies. grade IV and V adverse reactions occurred in all patients, In conclusion, combining sintilimab with neoadjuvant and the incidence of nausea and vomiting was the highest, chemotherapy has significant efficacy in treating middle followed by granulocytopenia and mucocutaneous damage, and advanced rectal cancer and is safer, which is conducive which was close to most of the previous similar reported to the subsequent surgery; and larger tumor diameter, higher data [17, 18]. The overall incidence of adverse reactions CEA level, higher TNM stage, and more serious lymphatic 6 Journal of Oncology metastasis are all independent risk factors affecting treat- tion in locally advanced rectal cancer with high risk of recur- rence - a phase II study,” Anticancer Research: International ment sensitivity and can lead to poor efficacy. Journal of Cancer Research and Treatment, vol. 37, no. 5, pp. 2683–2691, 2017. Data Availability [11] A. Bohlok, A. Hendlisz, F. Bouazza et al., “The potential benefit of adjuvant chemotherapy in locally advanced rectal cancer Data to support the findings of this study is available on rea- treated with neoadjuvant chemoradiotherapy is not predicted sonable request from the corresponding author. by tumor regression grade,” International Journal of Colorectal Disease, vol. 33, no. 10, pp. 1383–1391, 2018. Conflicts of Interest [12] T. Conroy, J.-F. Bosset, P.-L. 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Efficacy Analysis of Combining Sintilimab with Neoadjuvant Chemotherapy in Treating Middle and Advanced Rectal Cancer Based on Big Data

Efficacy Analysis of Combining Sintilimab with Neoadjuvant Chemotherapy in Treating Middle and Advanced Rectal Cancer Based on Big Data

Abstract

<i>Objective</i>. To analyze the efficacy of combining sintilimab with neoadjuvant chemotherapy in treating middle and advanced rectal cancer based on big data. <i>Methods</i>. According to the inclusion and exclusion criteria, 43 patients with middle and advanced rectal cancer, who were treated with sintilimab and neoadjuvant chemotherapy in General Surgery of the hospitals of Zhangjiakou city from January 2020 to January 2022, were selected for the retrospective study. The patients’ short-term efficacy was scientifically evaluated, and the factors affecting efficacy and the correlation were analyzed. <i>Results</i>. Among the 43 enrolled patients, 30 of them had regional lymphatic metastasis but none had distant metastasis; most patients were at Broders II and TNM III, and all of them had adenocarcinoma; the total response rate was 69.77% (30 cases), with no grade IV and V adverse reactions; the patients were divided into the effective group and the ineffective group after treatment based on the evaluation results of short-term efficacy, and analysis of the relevant factors exposed in both groups revealed significant differences in age, tumor size, CEA, NLR value, PLR value, TNM stage, and presence of combined lymphatic metastasis between the two groups (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M1" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>);</span></span> univariate analysis showed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were the independent risk factors affecting the efficacy in patients with middle to advanced rectal cancer (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M2" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-54"/></g></svg>);</span></span> and through the Spearman correlation analysis of the above independent risk factors, it was further confirmed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were negatively correlative with the efficacy of combining sintilimab with neoadjuvant chemotherapy in treating middle to advanced rectal cancer (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-54"/></g></svg>).</span></span> <i>Conclusion</i>. Combining sintilimab with neoadjuvant chemotherapy has good efficacy and safety profile, which is conducive to subsequent surgery; in contrast, larger tumor diameter, higher CEA level, higher TNM stage, and more serious lymphatic metastasis are all independent risk factors affecting treatment sensitivity and can lead to poor efficacy.

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Abstract

Hindawi Journal of Oncology Volume 2022, Article ID 8675587, 7 pages https://doi.org/10.1155/2022/8675587 Research Article Efficacy Analysis of Combining Sintilimab with Neoadjuvant Chemotherapy in Treating Middle and Advanced Rectal Cancer Based on Big Data 1 1 1 1 2 1 Yifei Wang, Jiandong Fei, Yanan Zheng, Ping Li, Xiaodong Ren, and Yongzhu An Department of Gastrointestinal Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000 Hebei, China Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000 Hebei, China Correspondence should be addressed to Yongzhu An; anyongzhu@hbbfyfy.com.cn Received 27 June 2022; Revised 9 August 2022; Accepted 25 August 2022; Published 16 September 2022 Academic Editor: Alamgeer Yuchi Copyright © 2022 Yifei Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To analyze the efficacy of combining sintilimab with neoadjuvant chemotherapy in treating middle and advanced rectal cancer based on big data. Methods. According to the inclusion and exclusion criteria, 43 patients with middle and advanced rectal cancer, who were treated with sintilimab and neoadjuvant chemotherapy in General Surgery of the hospitals of Zhangjiakou city from January 2020 to January 2022, were selected for the retrospective study. The patients’ short-term efficacy was scientifically evaluated, and the factors affecting efficacy and the correlation were analyzed. Results. Among the 43 enrolled patients, 30 of them had regional lymphatic metastasis but none had distant metastasis; most patients were at Broders II and TNM III, and all of them had adenocarcinoma; the total response rate was 69.77% (30 cases), with no grade IV and V adverse reactions; the patients were divided into the effective group and the ineffective group after treatment based on the evaluation results of short- term efficacy, and analysis of the relevant factors exposed in both groups revealed significant differences in age, tumor size, CEA, NLR value, PLR value, TNM stage, and presence of combined lymphatic metastasis between the two groups (P <0:05); univariate analysis showed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were the independent risk factors affecting the efficacy in patients with middle to advanced rectal cancer (P <0:05); and through the Spearman correlation analysis of the above independent risk factors, it was further confirmed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were negatively correlative with the efficacy of combining sintilimab with neoadjuvant chemotherapy in treating middle to advanced rectal cancer (P <0:05). Conclusion. Combining sintilimab with neoadjuvant chemotherapy has good efficacy and safety profile, which is conducive to subsequent surgery; in contrast, larger tumor diameter, higher CEA level, higher TNM stage, and more serious lymphatic metastasis are all independent risk factors affecting treatment sensitivity and can lead to poor efficacy. 1. Introduction tralia, and New Zealand and 392,000 new cases in China in 2018. Its early symptoms are not obvious, and the incidence is relatively high in men aged 40-80 years. At present, surgi- Rectal cancer is one of the most common malignant tumors of the digestive tract. According to the 2020 global epidemi- cal treatment is in the central position in rectal cancer treat- ment, because it provides patients at the early stage with ological statistics on cancer published by the International Agency for Research on Cancer (IARC), rectal cancer has long-term survival and those who can only receive limited treatment if they have local recurrence or distant metastasis become the 3rd most prevalent malignant tumor in men with better survival in combination with chemoradiotherapy and the 2nd in women worldwide, with the highest inci- dence in developed countries such as North America, Aus- [1]. For patients with locally advanced rectal cancer, 2 Journal of Oncology less than 3 months; (6) concurrent acute infection, such as neoadjuvant chemotherapy can lower the tumor stage, and some reports have confirmed that the application of neoad- lung infection and urinary system infection; (7) pregnant juvant chemotherapy before total mesorectal excision or lactating women; and (8) low compliance with treatment (TME) is the “gold standard” for the treatment of patients and lost to follow-up. with stage II and III rectal cancer [2, 3]. In addition, some 2.3. Patient Screening. According to the inclusion and exclu- published works and reports also state that neoadjuvant che- sion criteria, 43 patients with middle and advanced rectal motherapy has the potential to reduce local recurrence. In cancer, who were treated with sintilimab and neoadjuvant recent years, the studies of immune checkpoint inhibitors chemotherapy in General Surgery of the hospitals of Zhang- (ICIs) in various tumors are growing vigorously, and the jiakou city from January 2020 to January 2022, were selected results have shown that ICIs have good therapeutic effect. for the retrospective study; the study plan met the code of Immunotherapy is claimed to significantly improve the ethics and was reviewed and approved by the ethics commit- prognosis of colorectal cancer patients, and ICIs have also tees of the hospitals of Zhangjiakou city. been recommended as a first-line option for advanced rectal cancer [4–7]. Related studies suggest that ICIs show good 2.4. Methods effects in the neoadjuvant treatment of resectable rectal can- cer; meanwhile, ICI drugs also have a great potential in the 2.4.1. Sintilimab. Patients were treated with third-line and comprehensive treatment decision-making of locally above anti-PD-1 mAb monotherapy or in combination with advanced and early rectal cancer. In 2022, sindilizumab as other agents, the single dosage of sintilimab injection an innovative PD-1 inhibitor drug was successfully included (Tyvyt®) (specification: 100 mg; manufacturer: Innovent in the CSCO guidelines for the clinical use of ICIs, achieving Biologics (Suzhou) Co., Ltd.; NMPA approval no. the breakthrough that all first-line therapies for five major S20180016) was 200 mg, and it was administered once every tumors were included in the CSCO guidelines [8–10]. The 3 weeks until the downstaging effect and surgical resection use of immunotherapy in neoadjuvant treatment is mostly indicators were met, so as to improve the rate of radical dependent on the safety and efficacy of the treatment, and resection (R0 resection). it is still in the stage of active exploration from relevant data at home and abroad, with few clinical studies reported. 2.4.2. Neoadjuvant Chemotherapy. XELOX scheme: from Therefore, this article mainly collected middle and advanced day 1 to day 14, 1000 mg/m of capecitabine was given twice rectal cancer patients treated with sindilizumab plus neoad- daily; and at day 1, 130 mg/m of oxaliplatin was given. If a juvant chemotherapy in the General Surgery of the hospitals second course of chemotherapy was implemented, it should to carry out a retrospective study and to inquire about the be started at day 22 of radiotherapy. clinicopathological factors related to the treatment efficacy, avoiding ineffectiveness or overtreatment, which is also ben- 2.5. Observation Indicators. Clinical characteristics: the eficial to guide the preoperative treatment regimen and enrolled patients’ clinical information including age (with achieve the individualized treatment of middle and 55 years old as the critical value), gender, smoking, Broders advanced rectal cancer. classification, ECOG score, and TNM stage was recorded. Short-term efficacy: patients received reexamination after 4 weeks of treatment and were evaluated according to 2. Materials and Methods the WHO criteria for short-term objective response evalua- 2.1. Inclusion Criteria. (1) All patients were diagnosed with tion in solid tumors [11]. Complete disappearance of tumor middle and advanced rectal cancer after CT, MRI, and path- lesions and maintenance for ≥4 weeks were considered com- plete remission (CR); ≥30% reduction in volume of tumor ological examination; (2) the TNM stages of the patients were IIc and III; (3) the ECOG score was less than 3 points; lesions compared with that before treatment and mainte- (4) the patients had basically normal routine blood test nance for ≥4 weeks represented partial remission (PR); result, ECG, coagulation function, and liver and kidney <30% reduction in volume of tumor lesions compared with function; (5) the patients failed in first-line oxaliplatin+tar- that before treatment or <20% increase represented stable disease (SD); and ≥20% increase in volume of tumor lesions geted therapy chemotherapy and had not receive other PD-1 immunotherapy; (6) the patients did not have contra- compared with that before treatment or appearance of new indications of sindilizumab and chemotherapy; (7) the lesions represented progressive disease (PD), with total patients received TME after neoadjuvant chemotherapy; response = CR + PR. and (8) the patients and their family members understood Adverse reactions: according to the Common Terminol- ogy Criteria for Adverse Events (CTCAE) v4.0 of the the study and signed the treatment consent and study consent. National Cancer Institute (NCI) [12], the adverse reactions were divided into grades I to V (grade I: mild adverse reac- 2.2. Exclusion Criteria. Exclusion criteria are as follows: (1) tion, asymptomatic or mild symptoms, intervention not complicated with other malignant tumors; (2) complicated indicated; grade II: moderate adverse reactions, clinical with heart disease, severe hypertension, and other diseases symptoms that require intervention and may affect body of the cardiovascular system; (3) complicated with hemato- function, but daily life will not be affected; grade III: severe logical system diseases and severe internal medicine diseases; adverse reactions, complicated symptoms that require active (4) central nervous system metastases; (5) estimated survival intervention and treatment; grade IV: life-threatening Journal of Oncology 3 2.6. Statistical Processing. In this study, the data processing Table 1: Clinical characteristics of 43 patients (n =43). software was SPSS 22.0, which was mainly used to calculate Clinical data Number of cases Proportion (%) the between-group differences of data; the picture drawing Age software was GraphPad Prism 7 (GraphPad Software, San Diego, USA); the items included were enumeration data ≤55 years 20 46.51 and measurement data, which were expressed by ½nð%Þ >55 years 23 53.49 and (x ± s), examined by the X test and t-test, and met nor- Gender mal distribution; and differences were considered statisti- Male 28 65.12 cally significant when P <0:05. Female 15 34.88 Smoking 3. Results Yes 24 55.81 3.1. Clinical Characteristics. Among the 43 enrolled patients No 19 44.19 (aged 42 to 74 years) of the study, there were 28 males and Broders grade 15 females, 30 patients had regional lymphatic metastasis, I 4 9.30 and none had distant metastasis; most patients were at Bro- II 31 72.09 ders II and TMN III stage, all of them had adenocarcinoma. III 8 18.60 See Table 1 for statistical data. ECOG score 3.2. Short-Term Efficacy. All 43 patients finished sintilimab 0-1 point 26 60.47 treatment, neoadjuvant chemotherapy, and surgical treat- 2 points 17 39.53 ment and completed clinical efficacy evaluation. There were TNM stage 10 CR cases, 20 PR cases, 8 SD cases, and 5 PD cases and a IIc 13 30.23 total of 30 effective cases. See Figure 1. III 30 69.77 3.3. Adverse Reactions. After recording patients’ adverse reactions, it was found that patients did not have grade IV 69.77% and V adverse reactions, and the incidence rate of vomiting and nausea was the highest, followed by granulocytopenia and mucocutaneous damage. See Table 2. 46.51% 3.4. Analysis of Factors Related to Treatment Effectiveness. 23.26% The patients were divided into the effective group (n =30) 18.60% and the ineffective group (n =30) after treatment based on 11.63% the evaluation results of short-term efficacy, and analysis of the relevant factors exposed in both groups revealed signifi- CR PR SD PD Total efficac y cant differences in age, tumor size, CEA, NLR value, PLR value, TNM stage, and presence of combined lymphatic Figure 1: Evaluation results of patients’ short-term efficacy. metastasis between the two groups (P <0:05). See Table 3. 3.5. Logistic Regression Analysis. After including the single adverse reactions that may lead to disability and even organ factors into logistic regression analysis, it was showed that damage or dysfunction; grade V: death). tumor size, CEA, TNM stage, and lymphatic metastasis were Fasting venous blood was taken from all patients after independent risk factors affecting the efficacy of combining treatment and tested for white blood cell count (normal sintilimab with neoadjuvant chemotherapy in treating mid- range: 4:0 – 10:0×10 /L), neutrophils (normal range: 1:80 dle and advanced rectal cancer (P <0:05). See Table 4. 9 9 – 6:30 × 10 /L), lymphocytes (normal range: 0:8 – 4× 10 / L), platelets (normal range: 100 – 300 × 10 /L), CEA (normal 3.6. Correlation Analysis. After performing Spearman corre- range: 3.5–5.0 ng/mL), CA199 (normal range: <37 IU/mL), lation analysis of the above independent risk factors, it was NLR (normal range: 1–3), and PLR (normal range: 63.0– further confirmed that tumor size, CEA, TNM stage, and 182.6). combined lymphatic metastasis were negatively correlated The related factors, such as age (>55 years old), tumor with the efficacy of combining sintilimab with neoadjuvant size (≥3 cm), gender (male), distance between tumor and chemotherapy in treating middle and advanced rectal cancer anal verge (≥5 cm), concurrent chemotherapy cycle (≥3 (P <0:05). See Table 5. weeks), neoadjuvant chemotherapy cycle (≥2 weeks), white blood cell count, neutrophil, lymphocyte, platelet, CEA, 4. Discussion CA199, NLR value, PLR value, TNM stage, and lymph node metastasis, were included in the single variate analysis of In recent years, neoadjuvant chemoradiotherapy has gradu- treatment effectiveness, and then, logistic regression analysis ally walked into the popular field, and numerous previous and Spearman correlation analysis were performed. studies have shown that the comprehensive treatment mode (%) 4 Journal of Oncology Table 2: Evaluation results of patients’ adverse reactions. Adverse reactions Grade I Grade II Grade III Grade IV Grade V Total incidence rate½ n% ðÞ Nausea 17 2 0 0 0 19 (44.19) Vomiting 15 3 1 0 0 19 (44.19) Diarrhea 6 5 0 0 0 11 (25.58) Leukopenia 8 4 0 0 0 12 (27.91) Granulocytopenia 11 4 2 0 0 17 (39.53) Thrombocytopenia 3 3 0 0 0 6 (13.95) Mucocutaneous damage 10 4 1 0 0 15 (34.88) Neurotoxicity 9 2 0 0 0 11 (25.58) Peripheral phlebitis 4 1 0 0 0 5 (11.63) Table 3: Analysis of factors related to treatment effectiveness. Related factors Ineffective group (n =13)Effective group (n =30) X /t P Age (>55 years) 10 (72.92) 13 (43.33) 4.113 0.043 Gender (male) 7 (53.85) 21 (70.00) 1.042 0.307 Tumor size (≥3 cm) 8 (61.54) 8 (26.67) 4.721 0.030 Distance between tumor and anal verge (≥5 cm) 7 (53.85) 16 (53.33) 1.042 0.307 Concurrent chemotherapy cycle (≥3 weeks) 6 (46.15) 11 (36.67) 0.342 0.559 Neoadjuvant chemotherapy cycle (≥2 weeks) 8 (61.54) 16 (53.33) 0.248 0.619 3:82 ± 0:55 4:03 ± 0:68 White blood cell count (×10 /L) 0.981 0.332 Neutrophil (×10 /L) 3:04 ± 1:01 3:10 ± 1:04 0.175 0.862 0:90 ± 0:54 0:92 ± 0:49 Lymphocyte (×10 /L) 0.119 0.906 Platelet (×10 /L) 216:94 ± 60:16 218:33 ± 68:73 0.063 0.950 5:24 ± 1:48 2:64 ± 1:28 CEA (ng/mL) 5.836 <0.001 CA199 (IU/mL) 30:31 ± 12:16 23:85 ± 11:95 1.575 0.123 4:16 ± 0:62 3:61 ± 0:85 NLR value 2.098 0.042 PLR value 284:03 ± 13:85 270:11 ± 13:74 3.044 0.004 TNM stage 4.488 0.034 IIc 1 (7.69) 12 (40.00) III 12 (92.31) 18 (60.00) Lymphatic metastasis 12 (92.31) 18 (60.00) 4.488 0.034 Table 4: Multivariate logistic regression analysis. Variable B S.E. Wals df Sig. Exp (B) 95% C.I. of Exp (B) Tumor size -1.482 0.704 4.431 1 0.035 0.227 0.057-0.903 CEA (ng/mL) -1.240 0.376 10.904 1 0.001 3.457 1.656-7.218 TNM stage -2.079 1.106 3.538 1 0.006 0.125 0.014-1.091 Lymphatic metastasis -2.079 1.106 3.538 1 0.006 0.125 0.014-1.091 of neoadjuvant therapy combined with radical surgery has a chance of recurrence in some patients; in addition, it can relatively good effect on reducing the pathological stage of reduce the total number and positive rate of lymph nodes middle and advanced rectal cancer, lowering the rate of local in postoperative specimens, which is beneficial to the recurrence, prolonging survival time, and improving the rate improvement of the curative resection rate; and finally, neo- of anal conserving and the quality of life [13, 14]. Through adjuvant therapy reduces the tumor volume, increases the preoperative neoadjuvant chemoradiotherapy, it is able to distance between the lower edge of the tumor and the anal achieve postoperative pathological outcome as CR with low verge, and increases the success rate of anal-conserving Journal of Oncology 5 was not low but was within an acceptable range from the Table 5: Spearman correlation analysis. point of view of clinical treatment. The patients were divided Variable N Correlative coefficient Significance into the effective group and the ineffective group after treat- Tumor size 43 -0.331 0.030 ment based on the evaluation results of short-term efficacy, ∗∗ and analysis of the relevant factors exposed in both groups -0.664 CEA (ng/mL) 43 <0.001 revealed significant differences in age, tumor size, CEA, -0.323 TNM stage 43 0.035 NLR value, PLR value, TNM stage, and presence of com- -0.323 Lymphatic metastasis 43 0.035 bined lymphatic metastasis between the two groups (P <0:05); after including the single factors into logistic Note: ∗ indicated significant correlation at the 0.05 level (two-sided); ∗∗ indicated a significant correlation at the 0.01 level (two-sided). regression analysis, it was showed that tumor size, CEA, TNM stage, and combined lymphatic metastasis were the surgery. Meanwhile, concomitant with the continuous devel- independent risk factors affecting the efficacy of combining opment of medical treatment, ICIs represented by anti-PD-1 sintilimab with neoadjuvant chemotherapy in treating mid- dle and advanced rectal cancer (P <0:05); and after per- mAb have become a research hotspot for cancer therapy, and a pan-tumor clinical trial study found that patients with forming Spearman correlation analysis of the above mismatch repair dysfunction and high microsatellite insta- independent risk factors, it was further confirmed that bility might benefit from anti-PD-1 mAb therapy, but there tumor size, CEA, TNM stage, and combined lymphatic is still insufficient evidence, and immunotherapy strategies metastasis were negatively correlative with the efficacy of combining sintilimab with neoadjuvant chemotherapy in for rectal cancer are under continuous exploration. The advent of sindilizumab marks the entry of antitumor immu- treating middle and advanced rectal cancer (P <0:05). In notherapy in China into the innovation era. It is character- terms of TNM studies in malignant tumors, reports have ized by high affinity, long-lasting, stability and high target confirmed that the later the T stage of the tumor, the poorer occupancy, and the objective response rate and disease con- the efficacy [19–21]. As the course of the disease progresses, the depth of tumor infiltration trol rate of immunotherapy using this drug for relapsed and increases, the blood supply is refractory Hodgkin lymphoma are as good as those of inno- relatively insufficient, and the tumor cells suffer from poor vative drugs of the international class [15, 16]. At present, nutrition and hypoxia, which reduce the treatment radiotherapy combined with immunotherapy is the research sensitivity. hotspot of tumor regression, and the systemic immune The sensitivity of mAb therapy and chemotherapy is response induced before surgery can make the body produce dependent not only on the biological characteristics of immune memory, while after surgery, patients cannot pro- the tumor itself but also on the microenvironment in duce immune-mediated sustained antitumor effects due to which it resides. In vivo studies have found that tumor tumor resection, so neoadjuvant chemotherapy combined cells dying after chemoradiotherapy are able to present with immunotherapy is also rational to a certain extent. tumor associated antigens to host immune cells, activating Based on this, the efficacy of combining sindilizumab with the body tumor response. Therefore, hematological indices neoadjuvant chemotherapy in treating middle and advanced can also be an influential factor in the evaluation of recur- rectal cancer was explored herein, and the related factors rence and prognosis. The results of available studies sug- affecting efficacy were analyzed based on data. gest that neutrophils, NLR, lymphocytes, platelets, and The evaluation of clinical results of 43 patients revealed CEA have some correlation with the efficacy and clinico- that there were 10 CR cases, 20 PR cases, 8 SD cases, and 5 pathological characteristics of neoadjuvant chemoradio- PD cases, and the overall response rate of treatment was therapy and are somewhat valuable in judging the 69.77% (30 cases), which was higher compared with the pre- prognosis [22, 23]. CEA is widely used to predict the effi- vious results. On the one hand, the study result affirmed the cacy of neoadjuvant chemoradiotherapy for rectal cancer, efficacy of sindilizumab combined with neoadjuvant chemo- with demonstrated efficacy predictive value. The changes therapy in patients with medium and advanced rectal can- in NLR and PLR, novel systemic immune response indica- cer; on the other hand, because sindilizumab injection was tors, are caused by the synergistic effect of neutrophils, officially marketed in mainland China only in 2019 and the platelets, and lymphocytes. Relevant studies have shown duration of its clinical use for rectal cancer treatment is rel- that preoperative NLR levels and tumor volume size in atively short, so there are relatively few clinical cases. In cancer patients have significant associations [24, 25]. In addition, based on the study criteria, most of the enrolled this study, in logistic regression analysis and correlation patients were TNM stage III patients, some of them had analysis, the difference of NLR and PLR was not found, regional lymph node metastasis, and none had distant so the reference and guidance value of their level changes metastasis, and therefore, the specificity of case screening for the treatment of rectal cancer with the combination of may have some influence on the overall efficacy statistics. sindilizumab and neoadjuvant chemotherapy should be Based on the statistics of adverse reactions in patients, no confirmed with large-sample and multicenter studies. grade IV and V adverse reactions occurred in all patients, In conclusion, combining sintilimab with neoadjuvant and the incidence of nausea and vomiting was the highest, chemotherapy has significant efficacy in treating middle followed by granulocytopenia and mucocutaneous damage, and advanced rectal cancer and is safer, which is conducive which was close to most of the previous similar reported to the subsequent surgery; and larger tumor diameter, higher data [17, 18]. The overall incidence of adverse reactions CEA level, higher TNM stage, and more serious lymphatic 6 Journal of Oncology metastasis are all independent risk factors affecting treat- tion in locally advanced rectal cancer with high risk of recur- rence - a phase II study,” Anticancer Research: International ment sensitivity and can lead to poor efficacy. Journal of Cancer Research and Treatment, vol. 37, no. 5, pp. 2683–2691, 2017. Data Availability [11] A. Bohlok, A. Hendlisz, F. Bouazza et al., “The potential benefit of adjuvant chemotherapy in locally advanced rectal cancer Data to support the findings of this study is available on rea- treated with neoadjuvant chemoradiotherapy is not predicted sonable request from the corresponding author. by tumor regression grade,” International Journal of Colorectal Disease, vol. 33, no. 10, pp. 1383–1391, 2018. Conflicts of Interest [12] T. Conroy, J.-F. Bosset, P.-L. 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Published: Sep 16, 2022

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