Influence of PD-L1 expression on the efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer.

BACKGROUND: Evidence on the influence of programmed death-ligand 1 (PD-L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) patients is at variance. METHODS: A single-center retrospective study was conducted to evaluate the influence of PD-L1 expression on the efficacy of EGFR-TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD-L1 expression level: PD-L1 < 1% (negative), PD-L1 1%-49% and PD-L1 ≥ 50%. The clinicopathological features, overall response rate (ORR), progression-free survival (PFS) and comutation information were collected and compared between the three subgroups. RESULTS: A total of 117 patients were included. For PD-L1 < 1%, PD-L1 1%-49% and PD-L1 ≥ 50% group, there were 39 (33.3%), 51 (43.5%) and 27 (23.0%) patients respectively, and the ORR was 43.2%, 64.0%, and 51.9%, respectively (p = 0.162), and the median progression-free survival (mPFS) was 22.0 months (95% CI: 14.0-29.9 months), 15.4 months (95% CI: 8.9-21.8 months) and 13.0 months (95% CI: 10.6-15.3 months), respectively (log-rank, p = 0.01). The mPFS was negatively correlated with PD-L1 expression level (r = -0.264, p = 0.041) and PD-L1 expression was an independent risk factor for worse PFS of EGFR-TKIs in multivariate Cox regression. Patients with concurrent TP53 mutation had shorter PFS (p = 0.039) and the patients harboring both mutant TP53 and positive PD-L1 had the shortest PFS (p = 0.006). CONCLUSIONS: The efficacy of EGFR-TKIs was influenced by the baseline PD-L1 expression. Higher PD-L1 expression was associated with shorter PFS. The combined indicators of TP53 and PD-L1 identified subgroups showing divergent benefits from EGFR-TKIs.

Afatinib and Dacomitinib Efficacy, Safety, Progression Patterns, and Resistance Mechanisms in Patients with Non-Small Cell Lung Cancer Carrying Uncommon EGFR Mutations: A Comparative Cohort Study in China (AFANDA Study).

(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations.

Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: A retrospective chart review.

Background: Synergistic anti-tumor effects were observed in vivo and in vitro when immune checkpoint inhibitors (ICIs) were combined with denosumab. However, the clinical benefit and safety of this synergy have not been adequately evaluated in non-small cell lung cancer (NSCLC). Methods: Consecutive charts of NSCLC patients with bone metastases between December 2020 and December 2021 in the Chinese National Cancer Center were reviewed. The entire cohort was divided into one experimental group (denosumab + ICIs [DI]) and three control groups (denosumab + non-ICIs [DnI], phosphates + ICIs [PI], phosphates + non-ICIs [PnI]). Real-world objective response rates (ORRs), median progression-free survival (mPFS), skeletal-related events (SREs), and adverse events (AEs) were compared between groups. Results: A total of 171/410 (41.7%) patients with advanced or recurrent NSCLC carrying bone metastases who received bone-targeted therapy were eligible for analysis. Although the DI group showed a better benefit trend, differences were not statistically significant concerning the therapeutic efficacy among the DI group (n = 40), PI group (n = 74), DnI group (n = 15), and PnI group (n = 42) (ORRs: 47.5%, 43.2%, 33.3%, and 40.5%, respectively, p = 0.799; and mPFS: 378, 190, 170, and 172 days, respectively, p = 0.115; SREs: 5%, 10.8%, 13.3%, and 11.9%, respectively, p = 0.733). Nevertheless, further analysis in the NON-DRIVER cohort revealed a greater benefit for the DI group (p = 0.045). Additionally, the AEs of the DI group were not significantly different from those of the PI, DnI, and PnI groups (AEs: 27.5%, 39.2%, 26.7%, and 28.6%, respectively, p = 0.742). Furthermore, the multivariate analysis revealed the independent prognostic role of DI treatment for PFS in the overall cohort. Within the DI group, we did not observe differences in benefit among different mutational subgroups (p = 0.814), but patients with single-site bone metastasis (p = 0.319) and high PD-L1 expression (p = 0.100) appeared to benefit more, though no significant differences were observed. Conclusions: Denosumab exhibited synergistic antitumor efficacy without increasing toxicity when used concomitantly with ICIs in patients with advanced non-small cell lung cancer carrying bone metastases.

A real-world study of dacomitinib in later-line settings for advanced non-small cell lung cancer patients harboring EGFR mutations.

OBJECTIVE: Dacomitinib has been approved for the first-line treatment of non-small cell lung cancer (NSCLC) carrying classical epidermal growth factor receptor (EGFR) mutations; however, real-world data on its later-line application are lacking. MATERIALS AND METHODS: Patients' data were retrospectively collected from the Chinese National Cancer Center and the PLA hospital between August 2019 and August 2021. Kaplan-Meier method and Log-rank test were utilized to assess progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analysis was conducted to determine prognostic indicators. RESULTS: In total, 56 NSCLC patients harboring EGFR mutations treated with later-line single dacomitinib or combinatory dacomitinib were enrolled. A total of 53 patients (94.6%) had treatment-related adverse events; eight patients (14.3%) had grade 3 or 4 events. Among 49 evaluable patients, 26.5% (13 patients) had a confirmed partial response and 73.5% (36 patients) had disease control; the median duration of follow-up was 9.6 months (95% confidence interval [CI], 8.4-10.8 months), the median progression-free survival was 5.4 months (95% CI, 3.5-7.3 months), and the half-year, 1-year, and 2-year OS rate were 79.2%, 70.6%, and 64.1%, respectively. Univariate analysis suggested that smoking, line of dacomitinib, and interval between last EGFR-tyrosine kinase inhibitor (TKI) and dacomitinib were associated with PFS and OS; chemotherapy between last EGFR-TKI and dacomitinib, and EGFR-TKI generation followed by dacomitinib were respectively associated with PFS and OS; multivariate analysis indicated chemotherapy between last EGFR-TKI and dacomitinib negatively affect PFS, and smoking and third-generation EGFR-TKI followed by dacomitinib negatively affect OS. CONCLUSIONS: This real-world study has shown that dacomitinib is active and well-tolerated in NSCLC patients harboring different EGFR mutations in later-line settings, even for those with brain metastases. Patients who benefited more from the first TKI were more likely to benefit from dacomitinib, and earlier application of dacomitinib after front-line TKI resistance may be considered.

Circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer: Predictors for response and prognosis.

BACKGROUND: The aim of the study was to define the clinical significance of circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer (SCLC) patients. METHODS: CTCs/CTECs and their subtypes were determined using SE-iFISH technology in 33 SCLC patients before initial treatment (B1), after two cycles of chemotherapy (B2), at the completion of chemotherapy (B3), and disease progression (B4). The correlations with clinical characteristics, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: CTCs and CTECs were detected in 96.6% and 65.5% of patients, respectively. Patients had higher levels of CTCs compared with CTECs in circulation (p < 0.05). Extensive-stage SCLC patients tended to have higher CTEC counts (p = 0.035), and the detection of CTC-white blood cell (CTC-WBC) clusters was associated with a worse response to treatment (p = 0.030). Patients with CTC-WBC clusters at B1 (17.3 vs. 22.6 months, p = 0.041) and B2 (19.9 vs. 25.2 months, p = 0.018) had significantly shorter OS than those with no detection. Additionally, their presence was revealed as independent predictors for a worse OS in multivariable analyses (B1: HR 9.3, 95% CI: 1.4-48, p = 0.0079; B2: HR 4.4, 95% CI: 1.1-18, p = 0.041). A high CTC level at B4 was an adverse prognostic factor for SCLC patients (PFS: 8.7 vs. 22.5 months, p = 0.0026; OS: 19 months vs. not reached, p = 0.0086). CTC clusters and CTECs also showed prognostic values. CONCLUSIONS: The presence of CTC-WBC clusters at baseline and after two-cycle chemotherapy and the total CTC counts at the completion of chemotherapy are strong predictors for the prognostic survival of SCLC patients receiving first-line treatment.

Changes and Influential Factors of Chemotherapy Usage for Non-Small Cell Lung Cancer Patients in China: A Multicenter 10-Year (2005-2014) Retrospective Study.

BACKGROUND: Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients. PATIENTS AND METHODS: The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors. RESULTS: A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets. CONCLUSION: From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.

Depth of Response was Associated with Progression-Free Survival in Patients with Advanced Non-small Cell Lung Cancer treated with EGFR-TKI.

Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate new therapeutic strategies in cancer. However, RECIST fails to assess the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as the maximum percentage change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or exon 19 deletion) treated with EGFR-TKI from August 2014 to July 2017 from two sites were retrospetively collected for analysis. Patients were divided into four groups by DepOR (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS against DepOR and the hazard ratio (HR) was determined through univariable and multivariable cox regression models. Results: In total, 265 patients were included for analysis. The number of patients in Group Q1-Q4 were 91 (34.3%), 73 (27.5%), 65 (24.5%) and 36 (13.6%), respectively. A greater DepOR was significantly associated with a longer PFS (Log-rank P<0.0001). The HRs (95% CI) for PFS comparing patients with different DepOR status were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3, and 0.33 (0.22-0.50) for Q4, all compared with patients in Q1. DepOR as a continuous variable was also associated with prolonged PFS (HR, 0.20; 95% CI, 0.13-0.33; P<0.001). Additionally, in the multivariable cox regression model, abnormal LDH, brain metastasis and male were found to be associated with worse PFS outcomes (P<0.05). Conclusion: A greater DepOR is significantly associated with PFS benefit in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to evaluate the response of targeted therapy.

Circular RNA profiling identified as a biomarker for predicting the efficacy of Gefitinib therapy for non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become important treatment options for non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. However, the detection of EGFR driver mutation is impeded by the lack of adequate tumor tissues, histopathological type, long detection period, and the heterogeneity of a tumor. Therefore, it is necessary to develop a more convenient method to guide the clinical use of EGFR-TKI. Circular RNAs (circRNAs) are characterized as a closed structure with covalently joined ends resistant to exonucleases may be a potential biomarker. In the present study, we aimed to screen circRNAs that may be associated with the efficacy of EGFR-TKI. METHODS: The expression of circRNAs sequenced by circular microarray in plasma samples between gefitinib effective and ineffective groups were compared. RT-qPCR further validated the results in an independent cohort. Kaplan-Meier curves were used to analyze the association between circRNA and progression-free survival (PFS) of NSCLC patients treated with gefitinib. RESULTS: In total, 52 NSCLC patients treated with gefitinib were included for analysis. 1,377 circRNAs were differentially expressed in gefitinib effective and ineffective groups, among which 989 circRNAs were up-regulated, and 388 circRNAs were down-regulated in the effective group. Furthermore, two differentially expressed circRNAs, hsa_circ_0109320 and hsa_circ_0134501, were validated by RT-qPCR in an independent cohort of 38 gefitinib-treated NSCLC patients. Elevated hsa_circ_0109320 was associated with longer PFS in gefitinib-treated NSCLC patients. CONCLUSIONS: Taken together, hsa_circ_0109320 may be a potential biomarker for the efficacy of EGFR-TKI in NSCLC patients. This provides a new molecular typing method for individualized precision treatment.

What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.

BACKGROUND: Most lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population. METHODS: We conducted a 10 years (2005-2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions. RESULTS: A total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P < 0.0001) and sputum with blood (P < 0.0001) than patients with other pathological types and clinical stages, respectively. Metastases pain (P < 0.0001) and neck and supraclavicular lymphadenectasis (P = 0.0006) were more likely to occur in patients with nonsquamous carcinoma than in patients with other carcinomas. Additionally, patients with stage IV disease had a higher percentage of chest pain, shortness of breath, dyspnea, weight loss, and fatigue than patients with other stages of disease. In multivariable logistic analyses, compared with patients with adenocarcinoma, patients with squamous carcinoma were more likely to experience symptoms (OR = 2.885, 95% confidence interval [CI] 2.477-3.359) but were less likely to present physical signs (OR = 0.844, 95% CI 0.721-0.989). The odds of having both symptoms and physical signs were higher in patients with late-stage disease than in those with early-stage disease (P < 0.0001). CONCLUSIONS: The symptoms and physical signs of lung cancer were associated with the stage and pathological diagnosis of NSCLC. Patients with squamous carcinoma were more likely to develop symptoms, but not signs, than patients with adenocarcinoma. The more advanced the stage at diagnosis, the more likely that symptoms or physical signs are to develop. Further prospective cohort studies are needed to explore these results.

Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: Overall design and results from a multicenter retrospective epidemiologic survey.

OBJECTIVES: This study aimed to explore the clinical profile and its trajectory of lung cancer on clinicopathological characteristics and medical service utilization in China. METHODS: Patients diagnosed with primary lung cancer in tertiary hospitals during 2005-14 were selected from seven geographic regions of China. Data on clinical characteristics and medical service utilization was extracted from medical record, and the ten-year trends were explored. RESULTS: A total of 7184 patients were included, the mean age was 58.3 years and the male-to-female-ratio was 2.7. From 2005 to 2014, the proportion of ≥60 year-old patients increased from 41.2% to 56.2% (p < 0.001). The smoking rate decreased from 62.9% to 51.1% (p < 0.001) and the proportion of females increased from 23.5% to 31.9% (p < 0.001). The proportion of advanced stage increased from 41.9% to 47.4% (p < 0.001). Adenocarcinoma's proportion increased from 36.4% to 53.5% (p < 0.001) while that of squamous carcinoma decreased from 45.4% to 34.4% (p < 0.001). The application of chest X-ray dropped from 50.2% to 31.0% (p < 0.001) but that of chest CT increased from 65.8% to 81.4% (p < 0.001). As two main treatment options, chemotherapy (p = 0.290) and surgery (p = 0.497) remained stable. The medical expenditure per patient increased from 40,508 to 66,020 Chinese Yuan (p < 0.001). CONCLUSIONS: The sustaining high smoking exposure, increasing proportion of female patients, advancing clinical stage, shifting of predominant pathology and increasing medical expenditure demonstrate potential challenges and directions on lung cancer prevention and control in China. Despite substantial changes of clinical characteristics, main treatment options remained unchanged, which needs further investigation.

Betulinic acid exerts potent antitumor effects on paclitaxel-resistant human lung carcinoma cells (H460) via G2/M phase cell cycle arrest and induction of mitochondrial apoptosis.

Betulinic acid is a pentacyclic plant compound obtained from the bark of white birch trees and has been demonstrated to exhibit notable pharmacological properties. In the present study, the anticancer potential of betulinic acid on paclitaxel-resistant lung cancer cell line (H460) was evaluated. Cell viability was evaluated by an MTT assay, and a clonogenic assay was performed to assess the effects on cancer cell colony formation. DAPI staining using fluorescence microscopy and flow cytometry were employed to evaluate the effects of betulinic acid on apoptosis. The effects of betulinic acid on the cell cycle and mitochondrial membrane potential were also evaluated by flow cytometry. The effects of betulinic acid on the protein expression of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X (Bax) were evaluated by western blot analysis. The results of the present study indicated that the half-maximal inhibitory concentration value of betulinic acid on paclitaxel-resistant H460 lung cancer cells was 50 µM. The treatment with betulinic acid was able to inhibit the colony formation potential in a dose-dependent manner. A lower cytoxicity by betulinic acid against normal human epithelial FR2 cells was observed compared with H460 cells. The betulinic acid exerted anticancer activity via the induction of apoptosis by regulating the Bcl-2/Bax signaling pathway. Additionally, treatment with betulinic acid resulted in cell cycle arrest of paclitaxel-resistant lung cancer H460 cells at the G2/M phase. Betulinic acid was also reported to cause reductions in the mitochondrial membrane potential in a dose-dependent manner. In conclusion, the results of the present study indicated that betulinic acid may be a useful drug candidate for the management of drug-resistant lung cancer.

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer.

OBJECTIVE: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. RESULTS: Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). CONCLUSIONS: The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

[Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer].

OBJECTIVE: To explore the association between different epidermal growth factor receptor (EGFR) mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer (NSCLC). METHODS: A retrospective cohort study was performed to assess 146 patients with advanced NSCLC at Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The first-line regimens included pemetrexed based chemotherapy (pemetrexed first-line therapy group, n = 79), pemetrexed based chemotherapy plus pemetrexed maintenance chemotherapy (pemetrexed maintenance therapy group, n = 38) and pemetrexed based chemotherapy plus tyrosine kinase inhibitors (TKI) maintenance therapy (TKI maintenance therapy group, n = 29). Median progression-free survival (PFS) was determined.For comparison, median PFS was evaluated for EGFR-positive,EGFR-negative versus EGFR mutation unknown NSCLC patients in first-line pemetrexed therapy and pemetrexed maintenance therapy groups. RESULTS: The median PFS was 4.6 (95%CI: 2.8-6.4), 9.8 (95%CI: 6.1-13.5) and 14.5 (95%CI: 11.8-17.2) months in pemetrexed first-line therapy, pemetrexed maintenance therapy and TKI maintenance therapy groups respectively (P = 0.000). No difference existed in PFS for pemetrexed first-line therapy group with a median PFS of 5.2 (95%CI: 2.8-7.7), 4.0 (95%CI: 0-10.8) and 4.6 (95%CI: 3.4-5.8) months respectively (P = 0.661). Among EGFR-positive,EGFR-negative and EGFR mutation status unknown patients in pemetrexed maintenance therapy group, the median PFS was 8.5 (95%CI: 4.0-13.1), 12.6 (95%CI: 11.6-13.7) and 8.0 (95%CI: 5.8-10.3) months with no significant statistical difference (P = 0.468). CONCLUSIONS: No significant difference exists in survival between different EGFR mutation status for pemetrexed based first-line chemotherapy. And TKI maintenance therapy is associated with better survival than pemetrexed maintenance therapy regardless of EGFR status.

[Clinical analysis of childhood and adolescent Hodgkin's lymphoma: a report of 88 cases].

OBJECTIVE: The aim of this study was to investigate the clinicopathological characteristics, effective treatment and prognosis in childhood and adolescent Hodgkin's lymphoma. METHODS: A total of 88 patients with childhood and adolescent Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005. The clinicopathological and follow-up data of the patients were retrospectively reviewed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. COX multivariate prognosis analysis was performed. RESULTS: The 2-year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free survival rate was 61.4%, and the 5-year overall survival rate was 95.5%. Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P = 0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033), chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall survival rate. Multivariate analysis showed that chemotherapy regimen (P = 0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation (P = 0.046) were independent prognostic factors of 5-year overall survival rate. CONCLUSIONS: The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation, associated with "B" symptoms and bulky disease are independent prognostic factors of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy regimen are independent prognostic factors of 5-year overall survival rate.

Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas.

PURPOSE: Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results. METHODS: Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks. Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy were evaluated. RESULTS: A total of 31 patients were enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade 3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively. PK analysis revealed t(1/2) of 16.8-18.3 h, T(max) of 1-2 h in most cases, and a dose-related increase in C(max) and AUC. Significant induction of histone H3 acetylation in peripheral white blood cells was observed after a single dose of chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular adenoid cystic carcinoma achieved a partial response. CONCLUSIONS: Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.

[Assessment of the protective effect of calcium-magnesium infusion and glutathione on oxaliplatin-induced neurotoxicity].

OBJECTIVE: To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin. METHODS: This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups. RESULTS: Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar. CONCLUSION: This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.

[Clinical characteristics and treatment of desmoplastic small round cell tumor].

OBJECTIVE: To investigate the clinical characteristics and treatment of desmoplastic small round cell tumor. METHODS: Five patients with DSRCT were diagnosed and treated in our Hospital from January 1999 to May 2009. Forty-eight cases with complete clinical data were collected and reviewed from 23 published reports. Therefore totally 53 patients with DSRCT were analysed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: The median age of all cases was 23 (1.5 - 66) years old at the time of diagnosis. 75.5% of patients were male. The most common presenting complaint was intra-abdominal mass or pain (77.4%). In 46 patients (86.8%), the primary tumor was located in the abdomen or pelvis. Fifteen (28.3%) had positive lymph nodes or distant parenchymal metastases. The median follow-up was 1.8 years (range, 0.1 - 10.0 years). The overall 1-, 3- and 5-year survivals were 45.8%, 20.8% and 5.7%, respectively. Forty-seven patients underwent surgery. Complete tumor resection was significantly correlated with long survival. The 1- and 3-year survival rates were 70.5% and 53.7% in patients treated with complete tumor resection compared to 37.2% and 4.8% in the incomplete tumor resection cohort (P = 0.0020). Thirty-four patients received chemotherapy and the 1- and 3-year survival rates were 60.1% and 35.2%, respectively, however, only 29.7% and 12.7% in patients without chemotherapy (P = 0.0396). Twelve patients had radiotherapy and the 1- and 3-year survival rates were 75.0% and 38.9%, respectively, compared with 36.9% and 14.8% in those without radiotherapy (P = 0.0314). CONCLUSION: Complete tumor resection results in improved survival in patients with DSRCT. Chemotherapy and radiotherapy correlate with improved patient outcome. Multimodal therapy may improve the survival in patients with DSRCT.

[Clinical analysis of 67 patients with brain metastases from breast cancer].

BACKGROUND & OBJECTIVE: The incidence of brain metastases from breast cancer seems to be increasing with the improvement of systemic control and survival prolongation. This study was to analyze the clinical characteristics, treatment modalities, and prognostic factors of brain metastases from breast cancer. METHODS: The time from primary diagnosis of breast cancer to brain metastases of 67 breast cancer patients were 0-15 years, and the median time was 2.5 years. Of the 67 patients, 3 received surgery plus radiotherapy, 30 received radiotherapy alone, 3 received chemotherapy alone, 26 received radiochemotherapy, and 5 received no treatment. Kaplan-Meier analysis and log-rank test were used to analyze survival status. RESULTS: Headache was the most common symptom of brain metastases from breast cancer. The median survival time was 4 years. After brain metastases, the median survival time was 11 months. Menstrual status, number of brain metastases, systemic metastases, and different treatment modalities had no correlations to survival time of the patients. CONCLUSIONS: The prognosis of brain metastases from breast cancer is still poor. Radiotherapy remains the standard treatment of brain metastases. The function of chemotherapy needs further study.