ABSTRACT
The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Neoplasm, Residual , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/geneticsABSTRACT
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 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 intention of breast reconstruction in breast cancer patients and explore the potentially-related impact factors.@*Methods@#Breast reconstruction related questionnaires were distributed among 525 women breast cancer patients in multiple centers. Proportion constitution, univariate analysis and Logistic regression analysis were applied to the returned data.@*Results@#84 valid questionnaires were collected. There were 35.1%(170/484) patients who had the intention of breast reconstruction, and the patients with no intention of reconstruction accounted for 40.7%(197/484), while 24.2%(117/484) of the patients showed an unclear attitude to breast reconstruction. The average cognitive and attitude scores of reconstructive patients were significantly higher than those without reconstructive wishes (t=8.194, P<0.05; t=13.795, P<0.05). The higher rate of breast reconstruction willingness in breast cancer patients was associated with a lower age (χ2=13.466, P<0.05) and a better educational background (χ2=14.955, P<0.05). The rate in in-service personnel was higher than that in unemployed personnel (χ2=12.744, P<0.05). The rate of breast reconstruction willingness in the patients with various family income and medical insurance categories was significantly different (χ2=10.551, P<0.05; χ2=4.255, P<0.05). The marital status and the place of residence had no relation to the rate of reconstruction willingness (P>0.05). A further Logistic regression analysis showed that there was a significant correlation between the intention of breast reconstruction and the following factors: the age of patients, family income, medical expense category, the attitude of breast reconstruction (P<0.05).@*Conclusions@#Breast cancer patients have severe lack of knowledge of breast reconstruction. However, the young patients, with good economic condition and a positive attitude to reconstruction had a strong desire for breast reconstruction. Therefore, it is necessary to strengthen the communication with breast cancer patients in clinical environment and improve the cognitive level of patients and their families to increase the rate of breast reconstruction.
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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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<p><b>OBJECTIVE</b>To discuss the necessity of MRI as a routine examination for diagnosis of glomus tumor.</p><p><b>METHODS</b>From Nov. 2013 to July 2014, 7 cases of glomus tumor were treated in our department. All patients had typical clinical symptoms of glomus tumor and received preoperative X-ray and/or MRI examination. The diagnosis was confirmed by postoperative histopathologic examination. All the patients were retrospectively analyzed by reviewing the preoperative examination results and PubMed search results.</p><p><b>RESULTS</b>2 cases underwent only X-ray examination before operation with no positive results. 3 cases underwent both X-ray and MRI. No positive finding happened in X-ray, while MRI showed glomus tumor characteristic on T1- and T2-weighted images which demonstreated a more intense signal after injection of gadolinium. The last 2 cases underwent only MRI examination, which revealed positive images of glomus tumor.</p><p><b>CONCLUSIONS</b>MRI plays an important role in diagnosis of glomus tumor and should be adopted as a routine examination.</p>