Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-Arm, Prospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. @*Materials and Methods@#This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. @*Results@#A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). @*Conclusion@#Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Efficacy and safety comparison of everolimus and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine therapy / 实用医学杂志

Objective To compare the efficacy and safety of everolimus combined with endocrine therapy and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine thera-py. Methods Ninety-three breast cancer patients were selected from January 2014 to February 2017. The primary end points were progression-free survival and clinical benefit rate and the secondary end points was tolerability. Re-sults The progression-free survival in fulvestrant group was slightly higher than that in the everolimus group(13.4 months vs 12.2 months,P = 0.297). The clinical benefit rates were 46.15% and 31.71% in fulvestrant group and everolimus group,respectively. Patients treated with fewer than 2 lines and endocrine resistant patients benefited more from fulvestrant but without statistical difference. The main adverse events related to everolimus were stomati-tis,with a prevalence rate of about 26% and a localized pneumonia with a prevalence rate of about 10%. The main adverse reaction of fulvestrant was the injection site reaction. Conclusions The efficacy of everolimus in combina-tion with endocrine therapy is not superior to that of fulvestrant for the treatment of advanced breast cancer pro-gressed after endocrine therapy. After weighing the clinical benefits and quality of life,fulvestrant may be better for patients treated with fewer than 2 lines and endocrine resistance.

Long-term Results for Sudden Cardiac Death Prevention of Implantable Cardioverter-defibrillator in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy / 中国循环杂志

Objective:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy,which may cause frequent ventricular arrhythmia or even sudden cardiac death (SCD).We observed the long-term follow-up result of high risk ARVC patients received an implantable cardioverter-defibrillator(ICD).Methods:We retrospectively collected ARVC patients with ICD who were treated in our hospital from 1996-12 to 2015-09 for their in-hospital and clinical records and conducted follow-up study.Results:A total of 39 ARVC patients were enrolled including 32 (82.1％) males,the mean age at diagnosis was (42.1±14.8) years and 33 (84.6％) patients suffered from persistent ventricular tachycardia (VT) or ventricular fibrillation (VF) prior to ICD therapy.The median follow-up time was 48.6 (32.3-73.3) months and 7 (7.7％) patients died during that period including 1 sudden death,1 heart failure and 1 cerebral infarction.28 (71.8％) patients received 540 appropriate ICD interventions,5 (12.8％) of them received the first appropriate ICD intervention more than 2 years after initial implantation procedure.12 (30.8％) patients experienced electrical storm and 7 (17.9％) of them with electrical storm more than 2 years after initial implantation procedure.The patients without broad precordial T wave inversion (TWI ≥V1～3) had a shorter eventfree survival period (HR=0.39,95％ CI 0.16-0.96).The application rates of antiarrhythmic drugs and radiofrequency catheter ablation before ICD therapy were similar in patients with or without appropriate ICD intervention,P＞0.05.Conclusion:High risk ARVC patients have frequent ventricular arrhythmia,ICD therapy could effectively stop VT/VF,which was the most reliable method to prevent sudden cardiac death.

Long-term Results for Sudden Cardiac Death Prevention of Implantable Cardioverter-defibrillator in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy / 中国循环杂志

Objective:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy,which may cause frequent ventricular arrhythmia or even sudden cardiac death (SCD).We observed the long-term follow-up result of high risk ARVC patients received an implantable cardioverter-defibrillator(ICD).Methods:We retrospectively collected ARVC patients with ICD who were treated in our hospital from 1996-12 to 2015-09 for their in-hospital and clinical records and conducted follow-up study.Results:A total of 39 ARVC patients were enrolled including 32 (82.1％) males,the mean age at diagnosis was (42.1±14.8) years and 33 (84.6％) patients suffered from persistent ventricular tachycardia (VT) or ventricular fibrillation (VF) prior to ICD therapy.The median follow-up time was 48.6 (32.3-73.3) months and 7 (7.7％) patients died during that period including 1 sudden death,1 heart failure and 1 cerebral infarction.28 (71.8％) patients received 540 appropriate ICD interventions,5 (12.8％) of them received the first appropriate ICD intervention more than 2 years after initial implantation procedure.12 (30.8％) patients experienced electrical storm and 7 (17.9％) of them with electrical storm more than 2 years after initial implantation procedure.The patients without broad precordial T wave inversion (TWI ≥V1～3) had a shorter eventfree survival period (HR=0.39,95％ CI 0.16-0.96).The application rates of antiarrhythmic drugs and radiofrequency catheter ablation before ICD therapy were similar in patients with or without appropriate ICD intervention,P＞0.05.Conclusion:High risk ARVC patients have frequent ventricular arrhythmia,ICD therapy could effectively stop VT/VF,which was the most reliable method to prevent sudden cardiac death.

Clinical Features and Outcomes of Cardiac Resynchronization Therapy in 16 Patients With Dilated-phase Hypertrophic Cardiomyopathy / 中国循环杂志

Objective: To analyze the clinical features and outcomes of cardiac resynchronization therapy (CRT) in patients with dilated-phase hypertrophic cardiomyopathy (DHCM). Methods: A total of 16 DHCM patients received CRT in our hospital from 2007-03 to 2016-01 were retrospectively studied to analyze their clinical features and outcomes. Results: There were 12 male and 4 female patients at the mean age of (53.3±13.5) years. Pre-operative QRS duration of ECG was (158.7±32.2) ms, left ventricular ejection fraction (LVEF) was (33.6±6.3) %, the patient with NYHA class I, II, III and IV were 1, 5, 8 and 2 respectively. 13 patients received new CRT device, 3 received upgraded device and 8 (50%) combining atrial fibrillation (AF). The patients were followed-up for (2.56±2.13) years, 5 of them died including 3 of heart failure, 1 of sudden death and 1 of stroke. At 6 months follow-up time, 7 patients had the response to CRT which was defined by the improvement of NYHA class≥1 and the absolute elevation of LVEF≥5%; NYHA class improved from (2.69±0.79) to (2.38±0.89), P=0.02; LVEF increased from (33.6±6.3) % to (40.03±9.83) %, P=0.01. Conclusion: DHCM patients with CRT indication had the higher incidence to suffer from AF, those were more in patients with traditional pacemaker or ICD upgrading. DHCM patients with CRT had the poor general prognosis, while there was still certain proportion of patients had the response to CRT.

Predictor Analysis for Super-response to Cardiac Resynchronization Therapy / 中国循环杂志

To analyze the predictors and prognosis for super-response to cardiac resynchronization therapy (CRT) in patients with different etiology. Methods: A total of 181 patients received CRT in our hospital from 2012-01 to 2016-01 were enrolled. The patients were divided into 3 groups: Non-response group, n=63, Response group, n=62 and Super-response group, n=56. The patients were followed-up at 6 months after CRT. Results: There were 30.9% (56/181) patients having super-response. Compared with the other 2 groups, Super-response group had more patients with NYHA II-III and less NYHA IV, the patients were with the smaller LAD, LVESD, LVEDD andless patients had CRT-D implantation. The baseline cardiac function was obviously improved at 6 months after CRT in all 3 groups. The basic LVEDD, LVESD, CRT-D implantation, non-ischemic cardiomyopathy (NICM) and NYHA IV were the independent predictors for super-response occurrence. In addition, compared with ischemic cardiomyopathy (ICM), NICM patients had the higher ratio for super-response occurrence (37.6% vs 7.5%), P<0.001. Survival analysis indicated that NICM patients had the lower risk of all cause mortality (HR=0.31, 95% CI 0.14-0.80), cardiac death (HR=0.27, 95% CI 0.09-0.48) and combined endpoints (HR=0.36, 95% CI 0.27-0.78). Conclusion: At baseline condition, the patients with less degree of left ventricular reconstruction, CRT-D implantation, NICM and NYHA IV had more chance to suffer from super-response after CRT. NICM patients had the better response and prognosis to CRT.

Acute and Chronic Changes and Predictive Value of Tpeak-Tend for Ventricular Arrhythmia Risk in Cardiac Resynchronization Therapy Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prolongation of the Tpeak-Tend (TpTe) interval as a measurement of transmural dispersion of repolarization (TDR) is an independent risk factor for chronic heart failure mortality. However, the cardiac resynchronization therapy's (CRT) effect on TDR is controversial. Therefore, this study aimed to evaluate CRTs acute and chronic effects on repolarization dispersion. Furthermore, we aimed to investigate the relationship between TpTe changes and ventricular arrhythmia.</p><p><b>METHODS</b>The study group consisted of 101 patients treated with CRT-defibrillator (CRT-D). According to whether TpTe was shortened, patients were grouped at immediate and 1-year follow-up after CRT, respectively. The echocardiogram index and ventricular arrhythmia were observed and compared in these subgroups.</p><p><b>RESULTS</b>For all patients, TpTe slightly increased immediately after CRT-D implantation, and then decreased at the 1-year follow-up (from 107 ± 23 to 110 ± 21 ms within 24 h, to 94 ± 24 ms at 1-year follow-up, F = 19.366,P< 0.001). No significant difference in the left ventricular reverse remodeling and ventricular tachycardia/ventricular fibrillation (VT/VF) episodes between the TpTe immediately shortened and TpTe immediately nonshortened groups. However, patients in the TpTe at 1-year shorten had a higher rate of the left ventricular (LV) reverse remodeling (65% vs. 44%, χ2 = 4.495, P = 0.038) and less VT/VF episodes (log-rank test, χ2 = 10.207, P = 0.001) compared with TpTe 1-year nonshortened group. TpTe immediately after CRT-D independently predicted VT/VF episodes at 1-year follow-up (hazard ratio [HR], 1.030; P = 0.001).</p><p><b>CONCLUSIONS</b>Patients with TpTe shortened at 1-year after CRT had a higher rate of LV reverse remodeling and less VT/VF episodes. The acute changes of TpTe after CRT have minimal value on mechanical reverse remodeling and ventricular arrhythmia.</p>

Effect of Cardiac Resynchronization Therapy in Patients With Dispersion of Re-polarization and Ventricular Arrhythmia / 中国循环杂志

Objective: To explore the effects of cardiac resynchronization therapy (CRT) in patients with dispersion of re-polarization and ventricular arrhythmia. Methods: A total of 86 consecutive patents with CRT implantation were enrolled. According to weather absolute value of LVEF increased≥10% from baseline at 6 months after CRT implantation, the patients were divided into 2 groups: Response group and Non-response group,n=43 in each group. Dispersion of re-polarization indexes as QRS duration, QTc interval, TpTe interval and the events of ventricular arrhythmia were compared between 2 groups at different time points after CRT. Results:①In Response group, compared with pre-operation, QRS duration and TpTe interval were shorter at 1 year and within 24h after CRT implantation, allP0.05.②During 1 year after CRT implantation, the incidences of PVCs and PVC runs in Response group were much less than those in Non-response group, for lgPVCs: (1.78 ± 0.77) vs (2.73 ± 0.61), for lgPVC runs: (0.64 ± 0.48) vs (1.98 ± 0.72),P Conclusion: CRT ventricular reverse remodeling may reduce dispersion of re-polarization and the risk of ventricular arrhythmia, therefore improve the prognosis in relevant patients; TpTe interval within 24h after CRT had the predictive value for ventricular arrhythmia.

Operable Breast Cancer of the Inner Hemisphere Is Associated with Poor Survival / 한국유방암학회지

PURPOSE: This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes. METHODS: Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location. RESULTS: The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p<0.001). The association between tumor location and the 5-year DFS rate was most apparent in node-positive patients (73.1% vs. 65.8% for outer vs. inner hemisphere lesions, p<0.001) and in patients with primary tumors greater than 2 cm in diameter (78.2% vs. 72.3%, p=0.002). Multivariate analysis showed that tumor location was an independent predictor of DFS (hazard ratio [HR], 1.23; p=0.002) and OS (HR, 1.28; p=0.006). There were no significant differences in 5-year DFS or OS rates between patients with outer versus inner hemisphere tumors when internal mammary node irradiation was performed. CONCLUSION: This study demonstrated that tumor location was an independent prognostic factor for operable breast cancer. Internal mammary node irradiation is recommended for patients with breast cancer of the inner hemisphere and positive axillary lymph nodes or large primary tumors.

Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma / 癌症

<p><b>INTRODUCTION</b>An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC.</p><p><b>METHODS</b>By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed.</p><p><b>RESULTS</b>Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes: 7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis.</p><p><b>CONCLUSIONS</b>Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.</p>

The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer / 癌症

Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials--involving 11,456 adult patients in 32 arms--were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations (r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

SPARC expression and prognostic value in non-small cell lung cancer / 癌症

Secreted protein, acidic and rich in cysteine (SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value. Moreover, because of its strong affinity for albumin, and hence albumin-bound drugs, SPARC has increasingly become a focus for research. In this study, we aimed to determine SPARC expression in patients with non-small cell lung cancer (NSCLC) and investigate the association of SPARC with disease prognosis. Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center, and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression. Our results showed that SPARC expression status did not significantly relate with age, gender, and tumor stage. However, SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma (75% vs. 43.5%, P = 0.004). Patients with smoking history had higher SPARC expression than non-smokers (68.2% vs. 33.3%, P = 0.002). In both univariate and multivariate analyses, SPARC was a prognostic factor of overall survival (HR = 0.32; 95% CI: 0.16-0.65) but not disease-free survival. Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC. Most notably, SPARC can be used as a prognostic factor for NSCLC.

Expression of RRM1 and its association with resistancy to gemcitabine-based chemotherapy in advanced nasopharyngeal carcinoma / 癌症

Gemcitabine has high activity against nasopharyngeal carcinoma (NPC). The level of ribonucleotide reductase subunit M1 (RRM1) expression is closely related to the efficacy of gemcitabine on non-small cell lung cancer and pancreatic cancer. However, the expression of RRM1 and its association with sensitivity to gemcitabine-based chemotherapy in advanced NPC is not known. In this study, we retrospectively collected 48 formalin-fixed, paraffin-embedded NPC tissues to evaluate the expression of RRM1 using immunohistochemistry. All patients were diagnosed and treated with gemcitabine-based chemotherapy at Sun Yat-sen University Cancer Center. RRM1 expression was positive in 17(35%) patients. RRM1 expression was not associated with sex, age, performance status, WHO histological type, number of distant metastases, previous treatment, or cycles of gemcitabine-based chemotherapy(P> 0.05). The progression-free survival of the RRM1-positive group was shorter than that of the RRM1-negative group (5 months vs. 7 months, P = 0.036), and the response rate of the RRM1-positive group was somewhat lower than that of the RRM1-negative group (51.6% vs. 35.3%, P = 0.278). There was no significant difference in median survival between the RRM1-positive and RRM1-negative groups (22 months vs. 19 months, P = 0.540). Our results show that RRM1-negative expression is related with longer progression-free survival in advanced NPC patients treated with gemcitabine-based regimens.

Immediate versus delayed topotecan after first-line therapy in small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>How to prolong progression free survival (PFS) and overall survival (OS) of patients with small cell lung cancer (SCLC) has been one of the hottest issues. We retrospectively reviewed our data to compare the survival of immediate with delayed topotecan after first-line therapy in SCLC.</p><p><b>METHODS</b>In our retrospective study, 53 patients with SCLC were divided into two groups as follow: patients receiving topotecan-containing regimen as maintenance/consolidation (maintenance/consolidation chemotherapy group) and salvage chemotherapy (salvage chemotherapy group). The Log-rank test was used to assess the difference in OS between two groups. Cox regression model was used for the multivariable analysis of independent prognostic factors.</p><p><b>RESULTS</b>Twenty-nine patients received topotecan as maintenance/consolidation treatment, whereas 24 patients salvage chemotherapy. The response rates were 51.7% and 41.7%, respectively. The median survival time were 20 months and 27 months respectively (P = 0.89). Multivariate Cox regression analyses identified sex and stage as independent prognostic factors.</p><p><b>CONCLUSION</b>Efficacy of first-line therapy was improved by topotecan maintenance/ consolidation treatment, which did not result in any significant survival benefits in SCLC.</p>