1.Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study.
Xuhua HU ; Zhaoxu ZHENG ; Jing HAN ; Baokun LI ; Ganlin GUO ; Peiyuan GUO ; Yang YANG ; Daojuan LI ; Yiwei YAN ; Wenbo NIU ; Chaoxi ZHOU ; Zesong MENG ; Jun FENG ; Bin YU ; Qian LIU ; Guiying WANG
Chinese Medical Journal 2023;136(7):830-839
BACKGROUND:
The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection.
METHODS:
1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC.
RESULTS:
Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]).
CONCLUSIONS:
IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery.
TRIAL REGISTRATION
chictr.org.cn, ChiCTR 2100043775.
Humans
;
Fluorouracil/therapeutic use*
;
Leucovorin/therapeutic use*
;
Colorectal Neoplasms/pathology*
;
Retrospective Studies
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Proportional Hazards Models
;
Prognosis
2.Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis.
Jia HUANG ; Zhi Ying YANG ; Rui Li WEI ; Manar ATYAH ; Yong Liang SUN ; Li XU ; Wen Ying ZHOU
Chinese Journal of Surgery 2023;61(7):575-581
Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.
Male
;
Female
;
Humans
;
Pancreatic Neoplasms/surgery*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Retrospective Studies
;
Docetaxel/therapeutic use*
;
Liver Neoplasms/secondary*
;
Fluorouracil
;
Leucovorin/therapeutic use*
3.The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice.
Hao Chen ZHANG ; Xin Yi ZHOU ; Dong Liang FU ; Yu Wei DING ; Qian XIAO ; Ying YUAN
Chinese Journal of Oncology 2023;45(2):138-145
Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.
Animals
;
Mice
;
Antineoplastic Combined Chemotherapy Protocols
;
Apoptosis Regulatory Proteins
;
Colorectal Neoplasms/genetics*
;
Fluorouracil/pharmacology*
;
Irinotecan/therapeutic use*
;
Ki-67 Antigen
;
Oxaliplatin
;
Proto-Oncogene Proteins p21(ras)/therapeutic use*
4.Analysis of efficacy and prognosis of neoadjuvant chemotherapy and (or) surgery plus radiotherapy for hypopharyngeal squamous cell carcinoma.
Qihui XIAO ; Pin DONG ; Xinwei CHEN ; Xingjiang YING ; Yuyin LIU ; Lixiao CHEN ; Jian DING
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(9):700-707
Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma(HPSCC) and to compare the efficacy of surgical resection followed by adjuvant radiotherapy(SR) with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival(OS) of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender(P=0.850) had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio(PLR), neutrophil-to-lymphocyte ratio(NLR), T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis(P<0.05). The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC(P<0.05). Patients who received neoadjuvant therapy had longer OS than those who underwent SR only(P<0.001). There was no significant difference in tumor response to the two neoadjuvant therapies and in OS(P>0.05), and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups(P>0.05). Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.
Humans
;
Neoadjuvant Therapy
;
Squamous Cell Carcinoma of Head and Neck
;
Cetuximab/therapeutic use*
;
Retrospective Studies
;
China
;
Prognosis
;
Fluorouracil
;
Head and Neck Neoplasms
5.The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study.
Jing Jing DUAN ; Tao NING ; Ming BAI ; Le ZHANG ; Hong Li LI ; Rui LIU ; Shao Hua GE ; Xia WANG ; Yu Chong YANG ; Zhi JI ; Fei Xue WANG ; Yan Sha SUN ; Yi BA ; Ting DENG
Chinese Journal of Oncology 2023;45(11):967-972
Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans
;
Irinotecan/therapeutic use*
;
Oxaliplatin/therapeutic use*
;
Colorectal Neoplasms/pathology*
;
Retrospective Studies
;
Fluorouracil
;
Colonic Neoplasms/chemically induced*
;
Rectal Neoplasms/drug therapy*
;
Antineoplastic Combined Chemotherapy Protocols/adverse effects*
;
Camptothecin/adverse effects*
6.The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study.
Jing Jing DUAN ; Tao NING ; Ming BAI ; Le ZHANG ; Hong Li LI ; Rui LIU ; Shao Hua GE ; Xia WANG ; Yu Chong YANG ; Zhi JI ; Fei Xue WANG ; Yan Sha SUN ; Yi BA ; Ting DENG
Chinese Journal of Oncology 2023;45(11):967-972
Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans
;
Irinotecan/therapeutic use*
;
Oxaliplatin/therapeutic use*
;
Colorectal Neoplasms/pathology*
;
Retrospective Studies
;
Fluorouracil
;
Colonic Neoplasms/chemically induced*
;
Rectal Neoplasms/drug therapy*
;
Antineoplastic Combined Chemotherapy Protocols/adverse effects*
;
Camptothecin/adverse effects*
7.A novel chemotherapy strategy for advanced hepatocellular carcinoma: a multicenter retrospective study.
Juxian SUN ; Chang LIU ; Jie SHI ; Nanya WANG ; Dafeng JIANG ; Feifei MAO ; Jingwen GU ; Liping ZHOU ; Li SHEN ; Wan Yee LAU ; Shuqun CHENG
Chinese Medical Journal 2022;135(19):2338-2343
BACKGROUND:
Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC).
METHODS:
We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage.
RESULTS:
From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group ( P < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298-0.726; P = 0.001) and 0.474 (0.314-0.717; P < 0.001) after adjusting for potential confounders, respectively.
CONCLUSION
ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.
Humans
;
Carcinoma, Hepatocellular/drug therapy*
;
Retrospective Studies
;
Liver Neoplasms/pathology*
;
Oxaliplatin/therapeutic use*
;
Fluorouracil/adverse effects*
;
Disease Progression
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Leucovorin/adverse effects*
;
Colorectal Neoplasms/drug therapy*
8.Babao Dan Alleviates 5-Fluorouracil-Induced Intestinal Damage via Wnt/β-Catenin Pathway.
Meng-Xuan GUI ; Bin HUANG ; Jun PENG ; Xi CHEN ; Ragunath MUTHU ; Ying GAO ; Rui-Guo WANG ; Jiu-Mao LIN
Chinese journal of integrative medicine 2022;28(11):1000-1006
OBJECTIVE:
To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism.
METHODS:
A total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44).
RESULTS:
BBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01).
CONCLUSIONS
BBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis.
Animals
;
Male
;
Mice
;
Antineoplastic Agents/therapeutic use*
;
beta Catenin/metabolism*
;
Diarrhea/drug therapy*
;
Fluorouracil/pharmacology*
;
Intestinal Mucosa
;
Mucositis/metabolism*
;
Pentobarbital/therapeutic use*
;
Proliferating Cell Nuclear Antigen/metabolism*
;
Saline Solution
9.Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer.
Wei Li ZHANG ; Chi ZHOU ; Yu Xiang DENG ; Zhen Lin HOU ; Lin Jie ZHANG ; Jun Zhong LIN ; Zhi Zhong PAN ; Zhen Hai LU ; Jian Hong PENG
Chinese Journal of Gastrointestinal Surgery 2022;25(1):56-62
Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Camptothecin/therapeutic use*
;
Case-Control Studies
;
Colorectal Neoplasms/drug therapy*
;
Fluorouracil/therapeutic use*
;
Humans
;
Leucovorin/therapeutic use*
;
Liver Neoplasms/drug therapy*
;
Prognosis
;
Retrospective Studies
10.Utility of GPR68 and TIL in TPF-induced chemotherapy and prognosis evaluation in middle-advanced hypopharyngeal squamous cell carcinoma.
Lin CAO ; Meng Jiao ZHOU ; Yi Ming DING ; Ran GAO ; Xiao Hong CHEN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(2):178-184
Objective: To evaluate the roles of G Protein-Coupled Receptor 68 (GPR68) and tumor infiltrating lymphocytes (TIL) in TPF-(paclitaxel, cisplatin and 5-fluorouracil) induced chemotherapy for middle-advanced hypopharyngeal squamous cell carcinomas. Methods: A total of 31 patients with middle-advanced hypopharyngeal squamous cell carcinoma before TPF-inducted chemotherapy were enrolled from September 2012 to November 2017 in Beijing Tongren Hospital, Capital Medical University, including 28 males and 3 females, aged 43 to 71 years old. The expression of GPR68 and tumor infiltrating CD4+and CD8+T cells before chemotherapy was detected by immunohistochemical staining, and the relationships between GPR68 expression and clinical features, chemotherapy efficacy and overall survival (OS) were analyzed using t-test. Results: After 3 cycles of chemotherapy, there were 4, 14, 10 and 3 patients respectively with complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The positive rates of GPR68 and CD8 were 25% and 40% respectively in the effective group (CR+PR), while 50% and 15% in the ineffective group (SD+PD), with statistically significant differences between two groups (t=5.17 and 12.86,P<0.001). Linear regression analysis showed that GPR68 was negatively correlated with CD8+T cells (r=-0.64,P<0.001). There was no significant correlation between the CD4 expression and TPF efficacy (P>0.05). The mean OS was 12.5 months in patients with high-expressed GPR68 and 25.0 months in patients with low-expressed GPR68, with a statistically significant difference (P=0.005). And mean OS was 25.0 months in patients with high-expressed CD8 and 14.5 months in low-expressed CD8, with a statistically significant difference (HR=2.58, P=0.019). Cox regression analysis showed that GPR68 and CD8+T cells were significant prognostic factors (OR(95%CI)=3.27(2.46-5.97) and 1.53(0.78-1.82), all P<0.05), while CD4 had no significant effect on prognosis (P>0.05). Conclusion: GPR68 and CD8+T cells are expected to be biomarkers for evaluating the efficacy and prognosis of TPF-induced chemotherapy in patients with middle-advanced hypopharyngeal squamous cell carcinoma.
Adult
;
Aged
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Cisplatin
;
Female
;
Fluorouracil
;
Head and Neck Neoplasms/drug therapy*
;
Humans
;
Induction Chemotherapy
;
Lymphocytes, Tumor-Infiltrating
;
Male
;
Middle Aged
;
Prognosis
;
Receptors, G-Protein-Coupled
;
Squamous Cell Carcinoma of Head and Neck

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