OBJECTIVE：To investigate the ru les and characteristics of pembrolizumab-induced immune-related myocarditis ， and to provide reference for rational drug use in clinic. METHODS ：Using“pembrolizumab/keytruda”“myocarditis”“cardiotoxicity” “Pembrolizumab/Keytruda”“Cardiac toxicity ”“Myocarditis”“Cardiotoxity”“Cardiotoxicity”as Chinese and English retrieval words ， CBM，VIP，CNKI，Wanfang database ，PubMed，Wiley Online Library and Embase database were searched on the case reports of pembrolizumab-induced immune-related myocarditis during the inception to Aug. 2020. After eliminating the suspected case literature and repetitive literature ，gender，age，medication cause ，medical history ，drug combination ，drug dosage ，occurrence time of ADR ，clinical manifestation ，intervention measure and outcome of patients in the included literature were analyzed. RESULTS & CONCLUSIONS：A total of 15 literatures were included ，involving 13 English literatures and 2 Chinese literatures. Totally 15 patients were involved ，including 12 males and 3 females，with an average age of 71.35 years. There were 4 cases of non-small cell lung cancer ，4 cases of melanoma ，2 cases of bladder cancer ，1 case of urothelial cancer ，1 case of multiple osteosarcomas，1 case of gastric cancer ，1 case of thymic cancer ，1 case of nasopharyngeal carcinoma. There were 6 patients with previous medical history ，of which 5 had no history of heart disease and 1 had hypertension and hyperlipidemia ；there were 9 patients recorded the combined use of drugs ；the dosage and frequency of pembrolizumab were recorded in 12 patients. Immunological myocarditis of 93.3％ patients occurred after the first to second cycle of pembrolizumab administration ，and the average occurrence time was 15.5 days after the last administration. The most common clinical symptoms were dyspnea ，fatigue， dizziness or syncope. 9 patients showed cardiac block on electrocardiogram. All patients were treated with glucocorticoids when they developed immune-associated myocarditis ，and 5 patients died after hospitalization ；another one patient was restarted with pembrolizumab for one cycle after control of immune-related myocarditis ，but developed a recurrence of myocarditis and died of myocarditis ADR. It is suggested that baseline examination and routine monitoring of cardiac function should be done well when patients are treated with pembrolizumab. Once the patient is su spected to have immune-related myocarditis ，they should timely improve the cardiograms and other cardiac function-relatedtests，and start the treatment of high-dose glucocorticoids as 198177） soon as possible ，and are alert to the risk of death due to recurrence of myocarditis after readministration.

Objective To investigate the impact of the changes of posttreatment karnofsky performance status (KPSpost) on the overall survival (OS) for patients with stage Ⅳ non-small cell lung cancer (NSCLC) underwent concurrent chemoradiation.Methods A total of 279 patients (male 198 and female 81) with histological confirmed stage Ⅳ NSCLC were enrolled in this study with a median age of 58 years old (range 22 to 80 years old).There were 166 cases of squamous carcinoma,87 cases of adenocarcinoma,and 22 cases of unclassified carcinoma,respectively.All enrolled patients received more than 2 cycles of chemotherapy and more than 36 Gy of concurrent radiotherapy.Kaplan-Meier method and Log-rank test were applied to evaluate OS.Multivariate analyses were carried out by the Cox proportionalhazard model.Chi-square test and logistic regression analysis were used to explore the related factors of KPSpost.Results There were 198 patients with improved KPSpost and 81 patients with decreased KPSpost,respectively.Univariate and multivariate analyses indicated that the improvement of KPSpost was associated with longer OS.Logistic regression analysis showed that the improvement of KPSpost was positively related with treatment of more than 4-6 cycles chemotherapy concurrent with over 63 Gy radiation to primary tumor.The improvement of KPSpost also correlated positively with disease control rate (DCR),but negatively with PLT toxicity and radiation esophagitis.Conclusions KPSpost was an independent prognostic factor of OS for patients with stage Ⅳ NSCLC underwent concurrent chemoradiation.Chemotherapy of 4-6 cycles and concurrent over 63 Gy radiotherapy dose to primary tumor,as well as DCR were positive factors for KPSpost improvement.However,stage 3-4 PLT toxicities and radiation esophagitis decreased the KPSpost.

Objective To analyze the survival and toxicity after concurrent chemoradiotherapy in patients of different ages with stage Ⅳ non-small cell lung cancer (NSCLC).Methods Clinical data of 282 NSCLC patients in two prospective studies were retrospectively analyzed,who completed the protocol (at least 2 cycles of chemotherapy and thoracic radiation doses of ≥36 Gy).Among them,44 patients were assigned into in the young group (≤ 45 years old),161 patients in the middle-age group (46-64 years old) and 77 patients in the elderly group (≥ 65 years old).The clinical characteristics of patients among different groups were analyzed by x2 test.The overall survival (OS) was calculated by Kaplan-Meier method.Stratified analysis was performed by Log-rank test.Multi-factor prognosis analysis was conducted by Cox's proportional hazards regression model.Results The incidence of NSCLC in the male patients in the elderly group was higher than that in the middle-age and young groups.The 1-,2-,3-and 5-year OS did not significantly differ among different groups (P=0.810).The OS did not significantly differ among patients of the same gender,pathological type,T stage,N stage,metastasis status,same chemotherapy cycle,primary tumor dose and comprehensive treatment and short-term response (all P＞0.05).The incidence of adverse events did not considerably differ among different groups.Multivariate analysis demonstrated that age was not an independent factor for survival (P＞ O.05).Conclusion Patients of different ages with stage Ⅳ NSCLC obtain similar survival benefits and adverse events after concurrent chemoradiotherapy.

The efficacy of palliative care was definitive with two-dimensional radiotherapy for stage IV non-small cell lung cancer(NSCLC).However,theimpact of radiotherapy on survival was not well indicated,and some study resultsindicating prolonged survival were not accepted. Along with the advancesin three-dimensional radiotherapy (3DRT),wide application of comprehensive treatment,and the understanding of the association between different metastatic status and survival,prospective and retrospective studies have demonstrated that chemotherapy combined with 3DRT for primary tumor is more effective than chemoradiotherapy alone in improving symptoms and prolonging survival,especially for oligometastases of stage IV NSCLC.The dose to primary tumor is closely related to survival,and high-dose radiotherapy may be more likely to prolong survival. Further studies,however,areneeded to take into accountproblems such as thedose,timing,and technical selection of radiotherapy.

Objective To retrospectively analyze the effect of three-dimensional radiotherapy on the survival of patients with stage Ⅳ squamous cell lung cancer.Methods Of the 101 patients collected from two prospective phase Ⅱ studies, 88 were part of the per-protocol set.All patients received platinum-doublet chemotherapy with concurrent radiation to the primary tumor.Primary endpoints were overall survival (OS) and progression-free survival (PFS).Survival was calculated using the Kaplan-Meier estimator, and univariate and multivariate analyses were performed using the log-rank test and Cox model, respectively.Results The 1-, 2-, 3-, and 5-year OS rates of the 88 patients were 42.2%, 13.6%, 8.7%, and 3.1%, respectively, and the median survival time (MST) was 10 months.The 1-, 2-, 3-, and 5-year OS and MST at PTV dose ≥63 Gy were 45.7%, 25.7%, 17.1%, 7.1%, and 11 months, respectively, whereas the 1-, 2-, 3-, and 5-year OS and MST at PTV dose<63 Gy were 39.6%, 4.5%, 2.8%, 0%, and 10 months, respectively (P=0.007).The median PFS at ≥63 Gy and<63 Gy were 9 months and 7 months, respectively (P=0.032).The 1-, 2-, 3-, and 5-year OS and PFS of patients who received 4 cycles of chemotherapy at a PTV dose of ≥63 Gy were 51.9%, 29.6%, 18.5%, 9.9%, and 9 months, respectively (P=0.001 and P=0.012), which were significantly prolonged compared with other treatment modalities.Multivariate analysis showed that PTV ≥63 Gy may be influence the OS of patients (P=0.080).Conclusions Three-dimensional radiotherapy can prolong the survival of patients with stage ⅠV squamous cell lung cancer, as demonstrated by the gradual improvement in OS and PFS following the increase in the intensity of concurrent chemotherapy and radiation therapy.A PTV dose of ≥63 Gy may be influence the OS.

Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three?dimensional radiotherapy ( 3DRT) for stage IV non?small cell lung cancer ( NSCLC) . Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum?based doublets chemotherapy, with a median number of chemotherapy cycles of 4( 2?6 cycles) and a median dose of 3DRT of 60?3 Gy (36?0?76?5 Gy).The Kaplan?Meier method was used to calculate overall survival ( OS) rates, the log?rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1?, 2?, and 3?year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11?500?14?500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale ( KPS) after treatment significantly prolonged OS ( P=0?000,0?022,0?003, and 0?029) , and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0?058 and 0?075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS ( all P<0?05) . Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials. gov, registration number:ChiCTRTNC10001026.