Clinical analysis of leukemia secondary to malignant solid tumor in children / 国际儿科学杂志

Objective:To investigate the clinical characteristics, diagnosis and treatment and prognosis of children with leukemia secondary to malignant solid tumor.Methods:From January 2012 to January 2022, a total of 2 275 children under 15 years of age with malignant solid tumor were admitted to the First Affiliated Hospital of Zhengzhou University.Six children diagnosed with secondary leukemia after follow-up to August 1, 2022 were selected as the study objects.Their clinical data were retrospectively analyzed and the literature was reviewed.Results:(1)A total of 2 275 children with malignant solid tumors included 1 369 males and 906 females.There were 6 children with secondary leukemia, with an incidence rate of 0.26%, including 4 males and 2 females.The age of onset of solid tumor was 5.5(2.8, 9.7)years, and the age of secondary leukemia was(9.1±3.9)years, and the interval between them was(26.2±17.3)months.(2)Malignant solid tumor types: according to the time of secondary leukemia, there were hip malignant rhabdomyoma in 1 case, intracranial medulloblastoma in 2 cases, intracranial and pelvic malignant germinoma in 1 case respectively, and pancreatic blastoma in 1 case.Intracranial lesion biopsy was performed in 1 case, and tumor resection was performed in the other 5 cases.Three patients with intracranial tumors underwent local tumor bed, whole brain and spinal radiotherapy.All the 6 children received chemotherapy, and the main chemotherapy drugs were doxorubicin, vincristine, cyclophosphamide, platinum, ifosfamide, etoposide, bleomycin, temozolomide, etc.Complete remission was achieved in 3 cases, partial remission in 1 case, stable disease in 1 case, and disease progression in 1 case.(3)The secondary leukemia types were as follows: acute myeloid leukemia(AML)M5 in 3 cases, M1 in 1 case, M2 in 1 case, and acute B-lymphoblastic leukemia(B-ALL)in 1 case.All six cases refused hematopoietic stem cell transplantation(HSCT).One case with B-ALL gave up after receiving hydroxyurea and dexamethasone.Five cases with AML received chemotherapy according to the AML-2006 Protocol of Hematology Group of Pediatrics Society of Chinese Medical Association.The outcome of the disease was as follows: 2 cases died early, 4 cases achieved complete remission after 1 ~ 2 courses of chemotherapy, among which 2 cases did not continue treatment after 3 courses of chemotherapy due to pulmonary infection, deep mycosis, osteomyelitis, etc, and then recurred and died.By the end of follow-up, 2 cases survived and continued treatment, of which 1 case relapsed.After the diagnosis of secondary leukemia, the 1-year overall survival rate of the 6 cases was(33±26)%.Conclusion:Leukemia secondary to malignant solid tumors in children is rare and mostly occurs in older children.The pathogenesis is related to genotoxic injury caused by exposure to chemotherapy or radiotherapy, and the prognosis is unfavourable.HSCT after chemotherapy combined with immunotherapy is the best treatment strategy.

Efficacy and Safety of KRASG12C Inhibitors in Advanced Solid Tumors with KRASG12C-mutated: A Single-arm Meta-analysis / 肿瘤防治研究

Objective To systematically study the efficacy and safety of KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRASG12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRASG12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.

Radiological characteristics of hepatocellular carcinoma that achieved complete response after chemoembolization with drug-eluting beads for liver transplantation planning

ABSTRACT Objective To describe the radiological characteristics of hepatocellular carcinoma (HCC) lesions that achieved a complete response following drug-eluting bead transarterial chemoembolization (DEB-TACE) preceding liver transplantation. Methods This single-center case-control study enrolled patients with hepatocellular carcinoma who underwent neoadjuvant DEB-TACE therapy, were followed up with contrast-enhanced magnetic resonance imaging or computed tomography, and were successively evaluated according to the modified Response Evaluation Criteria in Solid Tumors. The HCCs were divided into two groups based on their diameter (Group A: ≤3cm; Group B: 3cm). Viability was assessed using the Kaplan-Meier method according to tumor size categories. The relationship between tumor variables was analyzed using bivariate Cox regression. Results Three-hundred and twenty-eight patients with 667 hepatocellular carcinomas who underwent their first DEB-TACE session were enrolled. A total of 105 hepatocellular carcinomas in 59 patients exhibited complete response after the initial DEB-TACE session and were divided into Group A (92 HCCs) and Group B (13 HCCs). The diameter in Group A decreased significantly compared to the pre-procedure size until the second assessment (p<0.001), with no subsequent reduction in diameter, despite maintaining a complete response. In Group B, the reduction in diameter remained significant compared with the initial value until the sixth imaging evaluation (p=0.014). The average reduction was 45.1% for Group B and a maximum of 14.9% in Group A. Conclusion HCCs >3cm exhibited a greater reduction in size and a longer time to recurrence. HCCs ≤3cm had a shorter relapse time. The recurrence rates were similar. These findings may aid in planning for liver transplantation.

Recent Progress of Nano-drug Combined with Chimeric Antigen Receptor T Cell Therapy in the Treatment of Soild Tumors / 中国肺癌杂志

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the background of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this filed.
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Expert consensus on off-label drug use in the three Northeastern provinces of China（solid tumors and hematology） / 中国药房

OBJECTIVE To provide theoretical basis for the rational use of drugs in medical institutions， assist in improving the quality of pharmaceutical services， and thus meet clinical drug demands. METHODS Adopting consensus meetings， Liaoning Pharmaceutical Association，Jilin Pharmaceutical Association and Heilongjiang Pharmaceutical Association collaborated with clinical and pharmaceutical experts in the region to compile the expert consensus on off-label drug use in the three Northeastern provinces of China after many votes and discussions by collecting and collating the information related to off-label drug use in medical institutions from the three northeastern provinces of China，and referring to and citing off-label drug use stated in some expert consensus and medication catalog. RESULTS Finally， a total of 198 pieces of off-label drug use information for 70 drugs were included in the two sections of solid tumors and hematological diseases in Consensus of Experts on Drug Use beyond the Instructions in the Three Provinces of Northeast China. CONCLUSIONS Consensus of Experts on Off-label Drug Use in the Three Northeastern Provinces of Northeast China （solid tumors and hematology）offers a theoretical foundation for rational drug use in the treatment of solid tumors and hematological diseases within medical institutions，and has a positive significance in improving the effectiveness and safety of drug treatment.

Serologically biochemical evaluation for patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid cancer treated by apatinib / 中华核医学与分子影像杂志

Objective:To analyze the relationship between serologically biochemical response and the disease progression trend and prognosis evaluated by traditional structural imaging in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated by apatinib.Methods:A retrospective study was performed on apatinib-treated (phase Ⅱ) patients ( n=19; 9 males, 10 females; age 46.0 (41.0, 57.5) years) with locally advanced/metastatic RAIR-DTC in Peking Union Medical College Hospital from March 2016 to June 2022. The relationships between serum thyroglobulin (Tg) and response evaluation criteria in solid tumors (RECIST) 1.1 structural imaging efficacy evaluation and disease progression trend were analyzed. The relationships between change of Tg after dose adjustment and the change of maximum diameter of target lesions in structure imaging were also discussed. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze the data. Results:During the median 49.41 months follow-up, the baseline Tg was 363.20(13.08, 2 490.50) μg/L. The Tg time-to-response was 0.47(0.47, 0.98) months, which was 1.80 (1.30, 1.90) months for RECIST 1.1. After 2, 4 and 8 weeks of initial treatment, the median Tg of the whole cohort decreased by 38.68%, 64.70% and 78.94%, respectively. After 8 weeks, the reducing degree of maximum diameter of target lesions was 33.48%. According to the best response, patients were divided into two groups: partial response (PR) group ( n=15) and stable disease (SD) group ( n=4). The median decreasing degree of Tg in PR group and that in SD group were 87.00% and 28.79%, and the reducing degree of maximum diameter of target lesions in corresponding groups were 45.00% and 21.22%. According to the final efficacy evaluation, patients were further divided into two groups: progressive disease (PD) group ( n=13) and non-PD (including PR and SD) group ( n=5). The median increasing degree of Tg in PD group was higher than that in non-PD group (381.55% vs 175.43%; U=10.00, P=0.037). The increasing degree of Tg and that of the maximum diameter of target lesions were 167.31% and 2.14% after the 1st adjustment, which were 231.06% and 9.73% after the 2nd adjustment. The differences of changes in Tg and maximum diameter of target lesions before and after the 1st dose adjustment were statistically significant ( z values: -3.06 and -2.23, P values: 0.002 and 0.026). Conclusion:During the apatinib treatment of RAIR-DTC, Tg can reflect the therapeutic effect of apatinib earlier than traditional imaging (RECIST 1.1), indicating the disease progression trend more sensitively.

Prognostic Value of Negative Lymph Nodes Count in Solid Tumors / 肿瘤防治研究

The postoperative pathological staging system (pTNM) has become an important reference for the selection of various tumor treatment strategies and prognosis evaluation at a global scale, and is a powerful predictor of the prognosis of a variety of solid tumors, but the prognosis is still different in patients with the same pTNM staging. In recent years, studies have confirmed that the negative lymph nodes count (NLNC) is related to the prognosis of a variety of solid tumors. Higher NLNC can improve the prognosis of cancer patients, and NLNC can reduce staging migration, which is expected to be a supplement to the pTNM staging system. This article reviews the value of NLNC in the prognosis of solid tumors.

Anti-tumor effects and cellular mechanisms of Pistacia atlantica methanolic extract against Ehrlich solid tumor in mice

Objective: To assess the anti-tumor effects of Pistacia atlantica methanolic extract (PAME) compared with cyclophosphamide against Ehrlich solid tumors in mice. Methods: Swiss albino mice (n=40) were divided into five groups: normal control mice, mice with Ehrlich solid tumors treated with normal saline, mice with Ehrlich solid tumors treated with cyclophosphamide intraperitoneally once a day for 14 d, or 50 mg/kg or 100 mg/kg PAME orally once a day for 14 d. Tumor growth inhibition, body weight, tumor markers, liver and kidney enzymes, oxidative stress markers, antioxidant enzymes, tumor necrosis factor-alpha level (TNF-α), and apoptosis-regulatory gene expression were evaluated. Results: Treatment of mice bearing Ehrlich solid tumors with PAME at 50 and 100 mg/kg orally significantly decreased tumor volume, body weight, tumor markers, liver and kidney enzymes, oxidative stress markers and TNF-α level in comparison with mice with Ehrlich solid tumors receiving normal saline. whereas PAME at 50 and 100 mg/kg/day significantly elevated the level of antioxidant enzymes (P<0.05). Conclusions: Pistacia atlantica methanolic extract has potent antitumor activity in mice. Therefore, the extract might be considered as an alternative anticancer agent against tumors, however, additional studies especially in the clinical setting are required to confirm this finding.

Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success? / 医学前沿

Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

Células asesinas naturales con el receptor de antígeno quimérico (CAR-NK): terapia emergente contra el cáncer / Chimeric antigen receptor-natural killer cells: novel therapy against cancer

Resumen Una de las herramientas más novedosas en inmunoterapias adoptivas contra leucemias y tumores malignos es el uso del receptor de antígeno quimérico "CAR". El receptor CAR ha sido ampliamente utilizada en células T (células CAR-T) potenciando su eficacia en el reconocimiento y eliminación de tumores, obteniéndose a la fecha terapias basadas en esta tecnología. No obstante, las células CAR-T llegan a repercutir negativamente en la salud del paciente, presentando el síndrome neurológico de efecto inmune asociado a células (ICANS) y el síndrome de lanzamiento de citocinas (SLC). Como consecuencia, el paciente necesita ser hospitalizado durante la terapia. Además, el coste de manufactura y terapia es elevado, siendo una tecnología limitada a un sector muy bajo de la población. En este trabajo, mencionamos el empleo de una terapia emergente de células asesinas naturales (NK) con el receptor CAR (CAR-NK), que cuentan con muchas ventajas por encima de las células CAR-T. Las células CAR-NK conservan su capacidad citotóxica en contra de tumores gracias a su acción dependiente de receptores activadores e inhibidores, por lo que el receptor CAR, solo estimula sus habilidades y persistencia. Sumado a esto, el coste de una terapia de células CAR-NK podría resultar redituable debido a la capacidad de las células CAR-NK de eliminar múltiples células tumorales sin generar daño colateral en el paciente. Aquí analizamos las características de los múltiples receptores CAR y los fenotipos de células NK que han sido utilizados durante múltiples ensayos (NK-92, células NK de sangre cordal y periférica, y células NK iPSC).

Abstract One of the novel and effective devices against leukemia and solid tumors in adoptive immunotherapies is the use of the chimeric antigen receptor "CAR". CAR technology has been widely used in T-cells (CAR-T cells) empowering its efficacy on the identification and elimination of tumor cells, getting today certain drugs based on this technology. Nevertheless, CAR-T cells can have a negative impact on patient health, causing in many cases immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS). As a consequence, the patient will have to be hospitalized for the duration of therapy. Moreover, the cost of manufacture and therapy is quite expensive, limiting its use to a low range of people. On the other hand, we analyze the advantages of Natural Killer cells with the CAR receptor (CAR-NK), which have many plusses over CAR-T cells. CAR-NK cells retain their cytotoxic abilities against tumor cells due their activator/ inhibitor receptors balance. Thus, the CAR receptor technology just increases their skills and persistence. Furthermore, CAR-NK therapy could be more profitable since CAR-NK can eliminate multiple tumor cells without generating collateral damage on patient health. Here, we discuss the characteristics of the multiples CAR receptors in general and the NK types cells that have been used in trials demonstrating their viable emerging therapy (NK-92, cord and peripheral blood NK cells, and iPSC-derived NK cells).

Detection of minimal residual disease using circulating tumor DNA in solid tumors:potential and challenges / 中华检验医学杂志

With the improvement of detective sensitivity, the application of circulating tumor DNA (ctDNA) has gradually expanded from advanced tumors to early stage. Recently, the detection of minimal residual disease (MRD) using ctDNA in solid tumors has attracted particular attention. MRD testing has shown an essential role in the risk assessment of solid tumor recurrence and treatment guidance. However, the MRD detection strategies used in each study are different, and the conclusions drawn as well. This paper reviewed the research progress of ctDNA for MRD detection in solid tumor, as well as its challenges of detection technology and application, in order to promote the clinical transformation and standardized application of MRD detection by ctDNA in solid tumors.

Value of Modified Response Evaluation Criteria in Solid Tumors response in predicting the prognosis of patients with unresectable hepatocellular carcinoma patients after transarterial chemoembolization / 临床肝胆病杂志

ObjectiveTo investigate the association of Modified Response Evaluation Criteria in Solid Tumors (mRECIST) response with the prognosis of patients with unresectable hepatocellular carcinoma (HCC) after transarterial embolization (TACE). MethodsA retrospective analysis was performed for the clinical data of 190 patients with unresectable HCC who were consecutively admitted to Department of Liver Disease and Digestive Interventional Radiology, The First Affiliated Hospital of Air Force Medical University, and treated with TACE from January 2010 to December 2014. The mRECIST criteria were used to evaluate imaging response after TACE; the patients with complete response (CR) or partial response (PR) were enrolled as response group(n=89), and those with progressive disease (PD) or stable disease (SD) were enrolled as non-response group(n=101). The Kaplan-Meier method was used to calculate median survival time, and the log-rank test was used for comparison between groups; the Cox regression model was used to identify the influencing factors for prognosis. ResultsAccording to the mRECIST criteria, 39 patients (20.5%) achieved CR, 50 (26.3%) achieved PR, 67 (35.3%) had SD, and 34 (17.9%) had PD. The objective response rate based on mRECIST was 46.8% for the whole population. The response group had a significantly longer survival time than the non-response group, and the median survival time was 29.9 (95% confidence interval ［CI］: 25.0-34.8) months for the response group and 7.5 (95% CI: 5.7-9.3) months for the non-response group (P＜0.001). The multivariate analysis showed that mRECIST response (hazard ratio ［HR］=2.02, P＜0.001), hepatitis B (HR=4.03, P＜0.001), and portal invasion (HR=2.12, P=0.008) were independent risk factors for survival. ConclusionThe mRECIST response has a certain value in predicting the prognosis of patients with unresectable HCC after TACE.

A single center study on the relationship between the depth of remission and the efficacy of first-line TKI drugs / 中国医师杂志

Objective@#The aim of the study was to investigate association of response depth and prognosis in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)patients treated with first-line tyrosine kinase inhibitors (TKIs).@*Methods@#The clinicopathological data and prognosis information of patients with locally advanced or metastatic (ⅢB or Ⅳ) lung adenocarcinoma with EGFR classical (19del or 21L858R) mutation who were treated in our hospital from 2015 to 2016 were collected. The tumor remission depth [stable disease (SD), partial response (PR), complete response (CR)] was measured by recist 1.1 standard. The survival curve was drawn by Kaplan-Meier method and log rank test was performed.@*Results@#During the study period, 204 advanced lung adenocarcinoma patients with 19del or 21L858R mutation were treated with TKI drugs of the first generation. Among them, 24 patients were lost or unable to evaluate the efficacy, 20 patients were evaluated as progression disease (PD), 62 patients as SD, 98 patients as CR or PR. Disease control rate (DCR) and objective remission rate (ORR) were 88.9% and 54.4%, respectively. The median progression free survival time (PFS) was 12.6 months (95% CI: 10.9-14.4 months) and 13.1 months (95% CI: 11.6-14.7) for patients assessed as SD (group A) and CR or PR (group B), respectively, with no significant difference (P=0.27). Subgroup analysis showed that the median overall survival of patients with EGFR 19del and 21L858R mutations was 12.5 months (95% CI: 9.9-15.4) and 12.7 months (95% CI: 9.4-16.1), respectively, with no significant difference (P=0.66); Similar result was also observed in Group B with a median PFS of 13.9 months (95% CI: 12.3-15.5 months) and 12.3 months (95% CI: 9.5-15.1 months) in patients who had EGFR 19del or 21L858R mutations (P=0.41).@*Conclusions@#Response depth was not a positive predictor for prognosis in EGFR-mutant NSCLC patients treated with first-line TKIs.

A single center study on the relationship between the depth of remission and the efficacy of first-line TKI drugs / 中国医师杂志

Objective The aim of the study was to investigate association of response depth and prognosis in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)patients treated with first-line tyrosine kinase inhibitors (TKIs).Methods The clinicopathological data and prognosis information of patients with locally advanced or metastatic (Ⅲ B or Ⅳ) lung adenocarcinoma with EGFR classical (19del or 21L858R) mutation who were treated in our hospital from 2015 to 2016 were collected.The tumor remission depth [stable disease (SD),partial response (PR),complete response (CR)] was measured by recist 1.1 standard.The survival curve was drawn by Kaplan-Meier method and log rank test was performed.Results During the study period,204 advanced lung adenocarcinoma patients with 19del or 21L858R mutation were treated with TKI drugs of the first generation.Among them,24 patients were lost or unable to evaluate the efficacy,20 patients were evaluated as progression disease (PD),62 patients as SD,98 patients as CR or PR.Disease control rate (DCR) and objective remission rate (ORR) were 88.9％ and 54.4％,respectively.The median progression free survival time (PFS) was 12.6 months (95％ CI:10.9-14.4 months) and 13.1 months (95％ CI:11.6-14.7) for patients assessed as SD (group A) and CR or PR (group B),respectively,with no significant difference (P =0.27).Subgroup analysis showed that the median overall survival of patients with EGFR 19del and 21L858R mutations was 12.5 months (95％ CI:9.9-15.4) and 12.7 months (95％ CI:9.4-16.1),respectively,with no significant difference (P =0.66);Similar result was also observed in Group B with a median PFS of 13.9 months (95％ CI:12.3-15.5 months) and 12.3 months (95％ CI:9.5-15.1 months) in patients who had EGFR 19del or 21L858R mutations (P =0.41).Conclusions Response depth was not a positive predictor for prognosis in EGFR-mutant NSCLC patients treated with first-line TKIs.

EGFR-CAR-T cells secreting PD-1 antibody significantly suppress the progression of gastric cancer / 中国肿瘤生物治疗杂志

@#[Abstract] Objective:To explore the anti-tumor effect of CAR-T cells secreting PD-1 scFv on gastric cancer. Method: We selected EGFR as the target of CAR-T cells and constructed second-generation EGFR-CAR-T cells (EGFR BB-z) and fourth-generation EGFR-CAR-T cells secreting PD-1 scFv (EGFR BB-z/E30). The anti-tumor activity was examined after in vitro activation and long-term stimulation, and its tumor suppression ability was validated through a mouse gastric cell xenograft model. Results: EGFR was highly expressed in gastric cancer tissues and cells (all P<0.01). EGFR BB-z and EGFR BB-z/E30 cells were successfully obtained by lentivirus infection. In vitro experiments showed that compared with EGFR BB-Z, EGFR BB-Z/E30 had longer long-term proliferation ability and stronger tumor killing activity (all P<0.01). In vivo experiments also validated that EGFR BB-z/E30 had obvious tumor inhibitory function in subcutaneous gastric tumor cell transplanted xenograft model and patient-derived tumor xenograft model (PDX) (all P<0.01). It also significantly increased T cell infiltration in tumor site and decreased the expression level of PD-1 (P<0.01 or P<0.05) on EGFR BB-z/E30 cell surface as well as the high secretion of IFN-γ (P<0.05). Conclusion: EGFR-CAR-T cell EGFR BB-z/E30 secreting PD-1 scFv can significantly inhibit the progression of gastric cancer and provide a potential new strategy for the treatment of gastric cancer.

Desarrollo de modelos educativos para el aprendizaje de nuevas técnicas endoscópicas: miotomía endoscópica por vía oral (POEM) y elastografía por ultrasonido endoscópico / Educational models for learning Peroral Endoscopic Myotomy (POEM) and Endoscopic Ultrasound Elastography

Resumen Objetivos: presentar el desarrollo de modelos educativos para el aprendizaje de dos técnicas endoscópicas vigentes, ampliamente difundidas y de gran implicación clínica, con la única intención de permitir la adquisición de destrezas básicas y avanzadas a residentes y gastroenterólogos. Materiales y métodos: se idearon dos modelos sencillos, de muy bajo costo, fácilmente reproducibles y reutilizables, con los cuales se logra ejecutar la totalidad de los procedimientos descritos. Además, permiten al operador integrar el desarrollo de habilidades y la adquisición de los conceptos teóricos mínimos requeridos, sin las presiones generadas por el riesgo existente de complicaciones. Resultados: la tendencia actual a nivel mundial se conduce hacia el desarrollo de modelos de enseñanza que aceleren la curva de aprendizaje, así como de procedimientos altamente exigentes y asociados a complicaciones potencialmente graves. Con estos modelos es posible poner a prueba al endoscopista, mediante una evaluación continua y supervisada. Su implementación en unidades de gastroenterología es sencilla, sin la necesidad de una inversión superlativa o el desplazamiento a otros países. Conclusiones: se trata de un gran aporte al desarrollo científico y educativo de nuestro país, ya que la creación y la implementación de nuevas técnicas endoscópicas y su aprendizaje no deben ser asumidos por los pacientes. En este punto, estamos de acuerdo con los conceptos emitidos por diferentes asociaciones médicas respecto a que los cursos teórico-prácticos de corta duración -y en algunas ocasiones virtuales- no constituyen una formación mínima, requerida para lograr la acreditación.

Abstract Objectives: This article presents the development of educational models for learning two widespread recent endoscopic techniques which have great clinical implications. Its sole intention is to allow acquisition of basic and advanced skills by residents and gastroenterologists. Materials and methods: Two simple, very low cost, easily reproducible and reusable models were devised. Procedures are fully described in ways that allow the operator to integrate the development of skills and acquisition of the minimum theoretical concepts required without the pressures generated by risks of complications. Results: The current global trend is to develop teaching models that accelerate the learning curve for highly demanding procedures that are associated with potentially serious complications. With these models it is possible to test endoscopists through continuous supervised evaluations. Implementation by gastroenterology units can be done easily without the need for large investments or travel to other countries. Conclusions: This is a great contribution to the scientific and educational development of Colombia since neither development of new endoscopic techniques nor the process of learning how to perform them should put patients at risk. We agree with the ideas of numerous medical associations regarding theoretical-practical courses of short duration even though some virtual sessions, "do not constitute the minimum training required needed for accreditation".

Crecimiento postraumático en pacientes sobrevivientes de cáncer infantil / (Posttraumatic growth in pediatric oncologic patients)

Resumen Objetivo: Estudiar el crecimiento postraumático en sobrevivientes pediátricos de linfoma o tumores sólidos, tratados en el Servicio de Oncología del Hospital Nacional de Niños, de enero de 1990 a diciembre 2013. Métodos: Este es un estudio descriptivo con pacientes sobrevivientes de cáncer quienes se encontraban en remisión, por un tiempo mayor o igual a 5 años. Se analizó las características clínicas de los pacientes (sexo, lugar de residencia, edad, tipo y localización del tumor, tratamiento recibido, presencia de metástasis o recaída), así como se efectuó una entrevista sobre la condición psicosocial de los sobrevivientes, con énfasis en las consecuencias de la enfermedad en su vida actual. Resultados: Se analizaron las características clínicas de 30 pacientes sobrevivientes. Se encontró que el tipo de tumor más común en el grupo entrevistado fue el linfoma no Hodgkin (30 %), seguido de sarcomas (20 %). Las localizaciones tumorales mayormente observadas en estos pacientes fueron en cabeza y cuello (46,7 %), seguidas por abdomen y pelvis (26,7 %). El tratamiento más frecuente fue la combinación de quimioterapia, radioterapia y cirugía (37,7 %). Pero cabe resaltar que el 80 % de los pacientes tratados recibió quimioterapia como parte de su tratamiento y la mayoría reportó efectos adversos y dificultades relacionadas. El procedimiento quirúrgico más empleado fue la biopsia (53,3 %). La mayoría de los pacientes no presentó recaídas (83,3 %) ni metástasis (93,3 %). Con respecto a su condición actual, la edad promedio al momento de la entrevista fue de 15,9 años, y la mayoría residía en la provincia de San José (40 %), con sus padres y hermanos (36,7 %). La mayoría señaló reacciones positivas ante el diagnóstico, con actitudes buenas y cooperadoras. El mayor vínculo socioafectivo descrito corresponde a la familia y los amigos; un grupo importante de los pacientes recalca el apoyo institucional. Conclusiones: A pesar de que con este trabajo no se pueden realizar generalizaciones sobre los pacientes en remisión de cáncer infantil, la información obtenida permite conocer de manera indirecta el impacto psicosocial de la enfermedad oncológica en la condición actual de un grupo de pacientes, y resalta una actitud positiva en los sobrevivientes.

Abstract Objective: To study resilience (post-traumatic growth) in pediatric cancer survivors who were treated in the Oncology Service of the National Children's Hospital, from January 1990 to December 2013. Methods: descriptive study with cancer survivors who were in remission, for a time greater tan or equal to 5 years. The clinical characteristics of the patients (sex, place of residence, age, type and location of the tumor, treatment received, presence of metastasis or relapse) were analyzed, as well as an interview on the psychosocial condition of the survivors, with emphasis on the consequences of the disease in their current life. Results: 30 survivors of childhood cancer were interviewed and the clinical characteristics were analized. Among the results, the most common type o tumor found was non Hodgkin lymphoma (30%), followed by sarcomas (20%). The tumor locations mostly observed in these patients were in the head and neck (46.7%), followed by the abdomen and pelvis (26.7%). The most frequent treatment was the combination of chemotherapy, radiotherapy and surgery (37.7%). But it should be noted that 80% of treated patients received chemotherapy as part of their treatment and the majority reported adverse effects and related difficulties. The most widely used surgical procedure was biopsy (53.3%). The majority of patients had no relapses (83.3%) or metastases (93.3%). Regarding their current condition, the average age at the time of the interview was 15.9 years, and the majority resided in the province of San José (40%), with their parents and siblings (36.7%). The majority indicated positive reactions to the diagnosis, with good and cooperative attitudes. The greatest socio-affective link described during their disease corresponds to family and friends and hospital health workers. Conclusions: Although, with this work, generalizations cannot be made about patients in remission of childhood cancer, the information obtained allows us to indirectly know the psychosocial impact of the oncological disease in the current condition of a group of patients in our country, and highlights a positive attitude in survivors.

Epigenetic therapies in patients with solid tumors: Focus on monotherapy with deoxyribonucleic acid methyltransferase inhibitors and histone deacetylase inhibitors

Epigenomics is the study of the gene expression changes due to epigenetic processes and not due to the deoxyribonucleic acid (DNA) base sequence alterations. The key mechanisms of epigenetic regulation include DNA methylation, histone modifications, and noncoding RNAs. Epigenetic alterations in cancer are predominantly linked with hypermethylation of promoters of the tumor suppressor genes, global DNA hypomethylation, and increased expression of histone deacetylases (HDAC). There is a growing need to investigate epigenetic patterns and to provide safe and effective, innovative therapeutic strategies for oncology patients, who did not improve on traditional anticancer regimens. The epi-drugs (e.g., DNA methyltransferase inhibitors, e.g., azacitidine and decitabine and HDAC inhibitors, e.g., vorinostat and romidepsin) have been approved for the clinical use. In this paper, we provide a brief overview of the mechanisms of action and targets for novel epi-drugs, focusing on their potential clinical applications in patients with solid tumors, resistant to standard oncology treatments

Early evaluate the feasibility and reproducibility of sorafenib-targeted therapy for hepatocellular carcinoma by volume measurement approach / 中华放射学杂志

Objective Early evaluate the feasibility and reproducibility of sorafenib-targeted therapy for hepatocellular carcinoma by RECIST1.1, mRECIST and three-dimensional volume measurement. Methods Seventy patients with pathology or typical imaging findings confirmed as hepatocellular carcinoma along with the sorafenib-targeted treatment for more than 2 months between October 2004 to April 2017 in the Fifth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Patients underwent chest, abdominal and pelvic CT scans and enhanced scans before and after 2 weeks of sorafenib treatment. Two physicians used RECIST 1.1, mRECIST, and volume measurement criteria to evaluate the efficacy of treatment. According to their averaged results, the patients were divided into two groups (control group and non-control group). Kaplan-Meier survival analysis was used to compare the prognostic values between different response evaluation criterias for early predicting the efficacy of sorafenib-targeted therapy in advanced hepatocellular carcinoma. Kappa test was used to assess the efficacy response consistency in intra-group and inter-group. Results Based on mRECIST and RECIST 1.1 measurements, the control group included 34 cases, and the non-control group included 36 cases. Based on semi-automatic volume measurement, the control group included 38 cases, and the non-control group included 32 cases. Before the treatment with sorafenib, the RECIST 1.1 and mRECIST methods were used. There was a high degree of consistency between the two doctors (Kappa values were 0.79 and 0.71, respectively), and the semi-automatic volume measurement method was extremely consistent (Kappa value was 0.90); the consistency in intra-observer by three different methods was extremely high (Kappa values were 0.91, 0.85, 0.97, respectively). After the treatment with sorafenib, the consistency between the two radiologists using RECIST 1.1 measurement was high (Kappa value was 0.65), the consistency of mRECIST measurement was moderate (Kappa value was 0.52), and the consistency of tumor volume measurement was extremely high (Kappa The value was 0.83), the consistency in intra-observer using the above three methods was high or very high (Kappa values were 0.86, 0.74, 0.90, respectively). The RECIST 1.1 and mRECIST measurements were less sensitive in early evaluation of sorafenib-targeted treatment, and there was no significant difference between the control group and the non-control group (P=0.578 and 0.613) while the semi-automatic volumetric measurement was sensitive (P=0.004). Conclusion Semi-automated three-dimensional volume measurement which has better intra-and inter-group consistency and reproducibility can reflect the efficacy of sorafenib-targeted therapy for hepatocellular carcinoma in early stage.