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Objective:To analyze the dosing, efficacy and safety of Regorafenib in elderly patients with metastatic colorectal cancer.Methods:Clinical data of 40 elderly patients with advanced colorectal cancer treated with regorafenib from June 2018 to October 2019 at Beijing Hospital were collected.The dosing, effectiveness and safety of regorafenib were retrospectively analyzed.The primary endpoint was overall survival(OS).Results:A total of 40 elderly patients were enrolled in this study, including 25 males and 15 females, with a median age of 66 years.The initial dose of Regorafenib was 80 mg, and the maintenance dose was 80 mg in 14(35.0%)patients, 120 mg in 20(50.0%)patients and 160 mg in 6(15.0%)patients.Thirty-one patients were treated with Regorafenib and 9 patients were given a combination therapy including Regorafenib.The objective response rate(ORR)was 2.5%(1 case), and the disease control rate(DCR)was 45.0%(18 cases). The median progression free survival(PFS)was 2.2 months(95% CI: 2.1-4.0)and the median OS was 8.8 months(95% CI: 7.1-11.2). There was no significant difference in PFS or OS in different maintenance dose groups( P<0.05). Patients who received 120 mg Regorafenib as a maintenance dose showed longest survival with a median OS of 9.8 months(95% CI: 6.9-14.0). There was no difference in median OS between the Regorafenib group and the combination therapy group( χ2=0.1, P>0.05). Grade 3 and 4 adverse reactions occurred in 11 patients(27.5%). Common adverse reactions were hand-foot skin reaction, fatigue, hypertension, diarrhea, elevated transaminase levels and proteinuria. Conclusions:Regorafenib offers a good survival benefit for elderly patients with advanced colorectal cancer who failed to respond to standard therapy.The dosing strategy, starting with a low dose of Regorafenib and escalating gradually as tolerance builds up, is recommended for elderly patients, when both efficacy and safety are considered.The proportion of patients who can tolerate 120 mg Regorafenib as a maintenance dose is high with relatively long overall survival, indicating it is appropriate for the elderly.
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Objective:To investigate the characteristics of gene mutations in colorectal cancer(CRC)patients by using next-generation generation sequencing(NGS).Methods:Blood and tissue samples were collected from 90 CRC patients admitted to Beijing Hospital between August 5, 2016 and December 29, 2020.Analysis of driver gene mutations was performed by using a 1021-gene NGS panel.Results:There were 43 tissue samples and 83 blood samples.Also, 36 patients had both tissue and blood samples.The frequency rates of KRAS and BRAF mutations were 51.2%(22/43)and 20.9%(9/43)in tissue samples, and 3 rare concomitant KRAS/ BRAF mutations were detected.The frequency rates of KRAS and BRAF mutations were 26.5%(22/83)and 10.8%(9/83)in blood samples.In patients with tissue and blood samples, the rates of KRAS and BRAF mutations were 52.8%(19/36)and 10.8%(8/36). Conclusions:The rate of KRAS mutations in tissue samples from colorectal cancer patients is similar to rates reported in the literature, but the rate of BRAF mutation and the rate of rare KRAS and BRAF co-mutations are higher than those reported from other countries.
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Objective:To investigate clinical features, diagnosis and treatment of angioimmunoblastic T-cell lymphoma(AITL)in middle and old age patients.Methods:This was a retrospective study.A total of 33 middle-aged and elderly patients(a median age of 64 years, range 47~85 years)with AITL admitted to our hospital from May 2008 to March 2017, including 54.5% male(18 cases), were enrolled in this study.Clinical manifestations, pathology, imaging and survival data of patients were collected.The objective response rate(ORR)of patients with different therapeutic regimens was analyzed.The survival analysis was conducted by using the Kaplan-Meier method, the survival rate was analyzed by using the Log-rank method, and multivariate analysis was conducted by using the proportional hazards regression model.Results:The median overall survival(OS)was 26.0 months(8.5-43.5 months). The 1-year, 3-year and 5-year OS rate was 66.7%(22 cases), 45.5%(15 cases)and 24.2%(8 cases), respectively.The ORR of first-line chemotherapy with CHOP-like regimens(cyclophosphamide, doxorubicin, vincristine, prednisone)was 65.5%(19/29)and the incidence of serious adverse reactions was 64.5%(20/31). Single-factor chi-square testing showed that age ≥60 years, Barthel score ≥90, Eastern Cooperative Oncology Group performance status score(ECOG-PS)≥2, anemia, International prognostic index(IPI)score of 4~5, receiving chidamide treatment were influncing factors for the prognosis in middle-aged and elderly patients with AITL( χ2=5.103, 4.306, 6.004, 4.030, 6.348 and 4.080, P<0.05). Cox multivariate analysis showed that age ≥60 years and receiving chidamide treatment were independent prognostic factors affecting the 5-year survival rate of middle-aged and elderly AITL patients( OR=0.313 and 4.964, P<0.05). That the OS was better in the group receiving chidamide treatment than in the group without chidamide treatment( P<0.05). Conclusions:Clinical features of AITL are diverse and lack of specificity.Most patients present with advanced stage AITL at the initial diagnosis.The 5-year OS rate is low.AITL patients aged over 60 years have a poor prognosis.Chidamide can improve the OS rate.
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Objective:To investigate the effect of a tankyrase inhibitor NVP-TNKS656 on the growth of hepatocellular carcinoma(HCC)cell lines and the involved molecular mechanisms.Methods:Five HCC cell lines were treated with 0, 2.5, 5.0, 10.0 μmol/L of NVP-TNKS656.The cell lines of HLE and HLF were selected and divided into four groups: 0.0 μmol/L(control or DMSO), 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L of NVP-TNKS656 groups.Cells were cultured for 48 h for subsequent experiments.Crystal violet staining was used to count the number of the newly formed cell clones.Western blotting was used to detect the protein expression levels of Yes-associated protein(YAP), angiomotin-like 1(AMOTL1)and AMOTL2.The real-time qRT-PCR was used to detect the mRNA expression of YAP and its downstream connective tissue growth factor(CTGF)and cysteine-rich 61(Cyr61). Dual luciferase reporter gene was used to detect the luciferase activity of transcriptional enhancer activator domain(TEAD)family.Results:NVP-TNKS656 inhibited the growth of 5 HCC cell lines in a dose-dependent manner in HLE, HLF, Huh7, MHCC97-H, and MHCC97-L cell lines.There were significant differences in the newly formed cell clone numbers between control(0 μM of NVP-TNKS656)and each of 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L of NVP-TNKS656 groups in a dose-dependent manner( F=90.46, 68.58, 191.8, 114.6 and 201.4, all P<0.05). In HLE and HLF cell lines, NVP-TNKS656 significantly reduced the protein level of YAP in a dose-dependent manner and decreased the YAP target gene CTGF(HLE cells: 1.02±0.02, 0.90±0.03, 0.57±0.02, 0.38±0.03, HLF cells: 0.98±0.03, 0.86±0.02, 0.66±0.02, 0.43±0.01)and Cyr61(HLE cells: 1.00±0.01, 0.86±0.02, 0.74±0.03, 0.44±0.03 and HLF cells: 0.99± 0.02, 0.87±0.01, 0.72±0.02, 0.54±0.01)( P<0.05), and inhibited the activity of YAP/TEAD luciferase.At the same time, NVP-TNKS656 up-regulated two major negative regulators of YAP, namely AMOTL1 and AMOTL2 proteins, and promoted the apoptosis of HLE and HLF cells in a dose-dependent manner. Conclusion:NVP-TNKS656 can inhibit the proliferation of HCC by stabilizing AMOTL1/ AMOTL2 and down-regulating the YAP target gene.This study indicates that NVP-TNKS656 can be used as a potential drug for treating HCC.
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Objective:To investigate the effect of a tankyrase inhibitor NVP-TNKS656 on the growth of hepatocellular carcinoma(HCC)cell lines and the involved molecular mechanisms.Methods:Five HCC cell lines were treated with 0, 2.5, 5.0, 10.0 μmol/L of NVP-TNKS656.The cell lines of HLE and HLF were selected and divided into four groups: 0.0 μmol/L(control or DMSO), 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L of NVP-TNKS656 groups.Cells were cultured for 48 h for subsequent experiments.Crystal violet staining was used to count the number of the newly formed cell clones.Western blotting was used to detect the protein expression levels of Yes-associated protein(YAP), angiomotin-like 1(AMOTL1)and AMOTL2.The real-time qRT-PCR was used to detect the mRNA expression of YAP and its downstream connective tissue growth factor(CTGF)and cysteine-rich 61(Cyr61). Dual luciferase reporter gene was used to detect the luciferase activity of transcriptional enhancer activator domain(TEAD)family.Results:NVP-TNKS656 inhibited the growth of 5 HCC cell lines in a dose-dependent manner in HLE, HLF, Huh7, MHCC97-H, and MHCC97-L cell lines.There were significant differences in the newly formed cell clone numbers between control(0 μM of NVP-TNKS656)and each of 2.5 μmol/L, 5.0 μmol/L, 10.0 μmol/L of NVP-TNKS656 groups in a dose-dependent manner( F=90.46, 68.58, 191.8, 114.6 and 201.4, all P<0.05). In HLE and HLF cell lines, NVP-TNKS656 significantly reduced the protein level of YAP in a dose-dependent manner and decreased the YAP target gene CTGF(HLE cells: 1.02±0.02, 0.90±0.03, 0.57±0.02, 0.38±0.03, HLF cells: 0.98±0.03, 0.86±0.02, 0.66±0.02, 0.43±0.01)and Cyr61(HLE cells: 1.00±0.01, 0.86±0.02, 0.74±0.03, 0.44±0.03 and HLF cells: 0.99± 0.02, 0.87±0.01, 0.72±0.02, 0.54±0.01)( P<0.05), and inhibited the activity of YAP/TEAD luciferase.At the same time, NVP-TNKS656 up-regulated two major negative regulators of YAP, namely AMOTL1 and AMOTL2 proteins, and promoted the apoptosis of HLE and HLF cells in a dose-dependent manner. Conclusion:NVP-TNKS656 can inhibit the proliferation of HCC by stabilizing AMOTL1/ AMOTL2 and down-regulating the YAP target gene.This study indicates that NVP-TNKS656 can be used as a potential drug for treating HCC.
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Objective:To investigate the influencing factors for the recurrence of TNM(T3~4N0M0)stage Ⅱ colorectal cancer in patients aged 75 years and over after radical resection.Methods:Clinicopathologic data of 161 colorectal cancer patients aged 75 years and over undergone radical resection in our hospital from January 2012 to August 2017 were retrospectively analyzed.They were followed up for 49 months(range: 2-84 months). Survival analysis was conducted by the Kaplan-Meier method and the survival rate was examined using the Log-rank method.Multivariate analysis was conducted by the proportional hazards regression model.Results:Univariate analysis showed that age≥80 years, preoperative comorbidities involving more than 1 system, weight loss≥10%, preoperative intestinal obstruction or perforation, preoperative CEA elevation, preoperative CA199 elevation, depth of primary tumor invasion T4, dissection of lymph nodes<12, vascular invasion, nerve invasion, deficient mismatch repair(dMMR), risk stratification and adjuvant chemotherapy were related factors for the prognosis in patients with TNM stage Ⅱ colorectal cancer aged 75 years and over after radical resection.Multivariate analysis showed that preoperative comorbidities involving more than 1 system, weight loss≥10%, preoperative intestinal obstruction or perforation, preoperative CEA elevation, depth of primary tumor invasion T4, dissection of lymph nodes<12 and vascular invasion were independent risk factors for poor prognosis, and adjuvant chemotherapy was an independent factor for favorable prognosis.The 5-year-disease-free survival(DFS)rate was 41.6% in all patients.The Kaplan-Meier curves indicated that disease-free survival(DFS)between the low-risk, middle-risk and high-risk groups had a statistically significant difference( χ2=14.632, P=0.001). Kaplan-Meier survival analysis showed that high-risk patients receiving Oxaliplatin combined with Capecitabine adjuvant chemotherapy had better DFS than those receiving Capecitabine or non-adjuvant chemotherapy( χ2=11.157, P=0.004). Conclusions:DFS is improved in strictly selected patients with stage Ⅱ colorectal cancer aged 75 years and over and at high risk who receive Oxaliplatin combined with Capecitabine adjuvant chemotherapy.
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Objective To investigate the clinical characteristics,prognosis,and influencing factors of digestive system tumors in elderly patients complicated with acute pulmonary thromboembolism(PTE).Methods In this retrospective cohort study,we analyzed data from 86 elderly patients with digestive system tumors from the Oncology Department of Beijing Hospital from January 2007 to January 2017.Forty-one elderly patients who had digestive system tumors with PTE were assigned into an observation group and forty five without PTE into a control group.We analyzed the clinical characteristics of the two groups.Kaplan-Meier survival analysis was used to assess the median survival time;and Cox regression analysis was used to evaluate the influencing factors for prognosis.Results Eighty-six elderly patients with a mean age of(75.8 ± 13.7)years ranging from 60 to 92 years were enrolled.There was a statistically significant difference in the D-dimer level between the groups at baseline (P ＜ 0.05).In the observation group,the primary symptom was dyspnea(78.0％,n=67).Of all primary tumors complicated with PTE,colorectal cancers had the highest prevalence,accounting for 56.1％ (n =23),followed by gastric cancers,representing 31.7％ (n=13).Twenty-three patients in the observation group were complicated with deep venous thrombosis(56.1％,n-23),which mostly located in the lower limbs (56.5 ％,n =23).Meanwhile,90.2 ％ of PTE(n =37) occurred during chemotherapy or follow-up.Sixty-seven patients (77.9 ％) died during the follow-up,and the difference in mortality between the two groups was statistically significant(P ＜ 0.05).Kaplan Meier survival analysis showed a significant difference in median survival time between the two groups (3.7 vs.8.5 months,P ＜ 0.05).Cox regression analysis indicated that age,PTE,and metastasis were risk factors for median survival time(all P ＜0.05) Conclusions Elderly patients with digestive system tumors complicated with acute pulmonary thromboembolism show no typical characteristics and poor prognosis.Therefore,preventive measures and care should be taken to improve the prognosis,especially for patients at high risk of PTE.
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Objective To explore the effect of related factors on survival of patients with unresectable pancreatic cancer aged 70 years and over. Methods Fifty-seven patients with unresectable locally advanced or metastatic pancreatic cancer aged 70 years and over were enrolled.Their survival time were analyzed with SPSS 13.0 by taking account of gender, age, smoking history,alcohol history, pancreatic disease history, diabetes mellitus history, Eastern Collaborative Oncology Group (ECOG) scoring, chemotherapy, radiotherapy, CEA and CA199 levels. Results Gender,ECOG scoring, chemotherapy and radiotherapy had relationship with overall survival. The median survival time was 8.9 months and one-year survival rate was 28.1%. The median survival was (10.7±5.4) months in male group and (5.5±2.3) months in female group (P=0.000). The median survival was(10.1±5.8) months in patients with ECOG 0～1 group and(7.3±3.8)months in patients with ECOG 2 group (P=0.040). The median survival was(7.76±5.27) months in nochemotherapy group and(11.5±5.0)months in chemotherapy group (P=0.038). The median survival was(8.87±5.36)months in no radiotherapy group and (13.7±3.8) months in radiotherapy group (P=0.048). Conclusions The patients who have better ECOG performance status and receive chemotherapy or radiotherapy show better survival.
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ObjectiveTo investigate mutations in exons 19, 20 and 21 of epidermal growth factor receptor (EGFR) gene in elderly patients with non-small cell lung cancer (NSCLC). MethodsEGFR gene mutations in exons 19, 20 and 21 were detected by nested PCR amplification and DNA sequencing in 46 elderly patients with non-small cell lung cancer. The relationship between mutations and clinical characteristics of these patients was analyzed. ResultsEGFR gene mutations were found in 56.5% (26/46) patients and 41.3% (19/46)were non-silent mutations. Mutation of exon 19 was detected in 6 cases (13.0%), mutation of exon 20 in 13 cases(28.2%) and that of exon 21 in 14 cases (30.4%). Seven patients among them had double mutations and the rest only had a single mutation. The incidence of EGFR gene mutations was higher in non-smokers than in smokers(P＜ 0.01). Higher EGFR mutation rate in exon 19, 20 and 21 were found in patients with clinical benefit who were treated with tyrosine kinase inhibitor(TKl)(P＜0.05). There was no difference in EGFR mutation rate between 60～69 age group and 70～85 age group. ConclusionsThe data suggest that the characteristics of EGFR gene mutations in elderly patients with NSCLC is the same as in the general NSCLC patients. The forecast informations of TKI treatment can be obtained by gene detection in elderly NSCLC patients.
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<p><b>BACKGROUND</b>To study the efficacy and long-term survival of high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (APBSCT) in the treatment of small cell lung cancer (SCLC)..</p><p><b>METHODS</b>Seven patients with pathologically confirmed SCLC were enrolled into the study, including 6 patients who had achieved CR or PR after conventional chemotherapy, and 1 patient who underwent surgical treatment and 6 cycles of conventional postoperative chemotherapy. All patients received a high-dose chemotherapy regimen of cyclophosphamide 6 g/m², etoposide 1.2 g/m², carboplatin 1.2 g/m² following APBSCT. Six of 7 patients received local radiotherapy after the procedure, however, another patient over 60 years did not receive local radiotherapy because of pneumonia complication. All patients were consecutively followed up and median follow-up duration was 27 (25-82) months.</p><p><b>RESULTS</b>Survival of the 7 patients was longer than 2 years. Three patients were still alive for more than 5 years after treatment, and the longest one up to 82 months. Three patients died and their survival time was 26, 27 and 27 months respectively.</p><p><b>CONCLUSIONS</b>High-dose chemotherapy supported by APBSCT combined with local radiotherapy may be helpful to prolong survival and improve prognosis for SCLC, especially to those patients with limited disease, relatively younger age and better performance status, and responding to conventional chemotherapy.</p>