Anlotinib as a third-line or further treatment for recurrent or metastatic nasopharyngeal carcinoma: a single-arm, phase 2 clinical trial.

BACKGROUND: Treatment options beyond the first-line setting for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are limited. The role of the multitarget tyrosine kinase inhibitor anlotinib in RM-NPC is unclear. METHODS: In this prospective, single-arm, phase 2 trial, patients with histologically confirmed RM-NPC and failure of at least two lines of prior systemic treatments were eligible. Anlotinib was given at 12 mg once daily on days 1-14 every 3 weeks until disease progression or intolerable toxicities. The primary end point was disease control rate, defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria. RESULTS: From April 2019 to March 2021, 39 patients were enrolled and received a median of 4 cycles (range, 0.5-20) of anlotinib treatment. Partial response and stable disease were observed in 8 and 20 patients, respectively. The disease control rate was 71.8%, and objective response rate was 20.5%. With a median follow-up of 17.2 months, the median progression-free survival was 5.7 months. The 12-month overall survival was 58.3%, and the median overall survival was not reached. The most frequent grade 3/4 treatment-related adverse events were hand-foot syndrome (23.7%), oral mucositis (21.0%), hypertension (7.9%), and triglyceride elevation (7.9%). Hemorrhage, all grade 1 or 2, occurred in 34.2% of the patients. CONCLUSIONS: Anlotinib monotherapy exhibited promising anti-tumor activities and disease control for heavily pretreated RM-NPC patients with a tolerable toxicity profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03906058.

Clinical significance of baseline Epstein-Barr virus DNA for recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75 patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survival and objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s) or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900 copies/ml) was related to shorter progression-free and overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.

Cultural adaptation and psychometric evaluation of the Chinese version of the nurse-specific end-of-life professional caregiver survey: a cross-sectional study.

BACKGROUND: Nurses' palliative and hospice care-specific education is associated with the quality of palliative and hospice care that influences health outcomes of patients with life-limiting illnesses and their caregivers. However, China lacks measures available to assess nurses' educational needs in palliative and hospice care. The End-of-Life Professional Caregiver Survey (EPCS) is a psychometrically reliable self-reporting scale to measure multidisciplinary professionals' palliative and hospice care educational needs. This study was performed to explore the psychometric properties of the Chinese version of the EPCS (EPCS-C) among Chinese nurses. METHODS: We translated and culturally adapted the EPCS into Chinese based on Beaton and colleagues' instrument adaptation process. A cross-sectional study design was used. We recruited 312 nurses from 1482 nurses in a tertiary hospital in central China using convenience sampling to complete the study. Participants completed the EPCS-C and a demographic questionnaire. Exploratory and confirmatory factor analysis was carried out to test and verify the construct validity of the nurse-specific EPCS-C. Cronbach's alpha coefficient was used to appraise the reliability of the nurse-specific EPCS-C. RESULTS: A three-factor structure of EPCS-C was determined, including cultural, ethical, and national values; patient- and family-centered communication; and effective care delivery. The exploratory factor analysis explained 70.82% of the total variances. The 3-factor solution of the nurse-specific EPCS-C had a satisfactory model fit: χ2 = 537.96, χ2/df = 2.96, CFI = 0.94, RMSEA = 0.079, IFI = 0.94, and GFI = 0.86. Cronbach's alpha coefficient of the overall questionnaire was 0.96. CONCLUSIONS: The nurse-specific EPCS-C showed satisfactory reliability and validity to assess nurses' palliative and hospice care educational need. Further research is required to verify the reliability and validity of the EPCS-C in a larger sample, especially the criterion-related validity.

Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations.

OPINION STATEMENT: The MET exon 14 skipping mutation is found in approximately 3% of lung adenocarcinomas and slightly more than 2% of lung squamous cell carcinomas. In recent years, more and more evidence has shown that MET inhibitors have achieved good anti-tumor effect in patients with MET exon 14 skipping mutation, suggesting that MET exon 14 skipping mutation may be a new target for NSCLC patients. Patients with positive MET exon 14 skipping mutation are recommended to be administered MET inhibitors, and crizotinib is recommended by the NCCN guideline. Due to the presence of gene amplification, second site mutation, bypass activation, and pathological type transformation, one of the inevitable problems of targeted therapy is drug resistance. If type I MET inhibitors (crizotinib, capmatinib, tepotinib, savolitinib) drug resistance is developed, type II MET inhibitors (cabozantinib, glesatinib, merestinib) can be considered.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Artificial intelligence for diagnosis and prognosis prediction of natural killer/T cell lymphoma using magnetic resonance imaging.

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.

CNS efficacy of afatinib as first-line treatment in advanced non-small cell lung cancer patients with EGFR mutations.

Background: Afatinib is a potent, irreversible second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has demonstrated efficacy in advanced non-small cell lung cancer (NSCLC) patients harboring either common or uncommon EGFR mutations. However, data on its activity against brain metastases are limited. This study aimed to retrospectively evaluate the efficacy and safety of afatinib as first-line treatment for EGFR-mutant NSCLC patients with brain metastases. Methods: Treatment-naive advanced NSCLC patients harboring EGFR mutations and brain metastases treated with afatinib were retrospectively reviewed to assess the central nervous system (CNS) efficacy and also the systematic benefits. Results: Totally 43 patients with measurable or non-measurable brain metastases were enrolled in the CNS full analysis (cFAS) set. Among them, 23 patients with measurable brain metastases were included in the CNS evaluable for response (cEFR) set. The CNS ORR was 48.8% (95% CI, 33.3 - 64.5%) in the cFAS set and 82.6% (95% CI, 61.2 - 95.0%) in the cEFR set, respectively. CNS mDoR was 8.9 months (95% CI, 4.7 - 13.1 months) and CNS mPFS was 12.7 months (95% CI, 6.9 - 18.5 months) in the cFAS set. In the subgroup analysis stratified by EGFR mutation types, CNS ORR of cEFR set in the common mutation cohort was 100% (95% CI, 75.3 - 100%) and 60% (95% CI, 26.2 - 87.8%) in the uncommon mutation cohort (p = 0.024); CNS ORR of cFAS set was 57.7% (95% CI, 36.9 - 76.6%) and 35.3% (95% CI, 14.2 - 61.7%), respectively (p = 0.151). CNS mPFS was 14.4 months in patients with common mutations and 6.1 months in patients with uncommon mutations (hazard ratio, 0.47; 95% CI, 0.22 - 1.00; p = 0.045). Patients with common mutations showed a significantly lower cumulative incidence of CNS failure than uncommon mutation cohort (p = 0.0026). Most of patients experienced grade 1/2 treatment-related adverse events. Conclusions: First-line afatinib demonstrated encouraging efficacy on brain metastases in NSCLC patients harboring either common or major uncommon EGFR mutations in a real-world setting, with manageable toxicities. Patients with common mutations showed better CNS outcomes than those with uncommon mutations.

Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Methods: Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. Results: A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). Conclusions: This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.

Novel target and treatment agents for natural killer/T-cell lymphoma.

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

Comprehensive view on genetic features, therapeutic modalities and prognostic models in adult T-cell lymphoblastic lymphoma.

Adult T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma that differs from pediatric T-LBL and has a worse prognosis. Due to its rarity, little is known about the genetic and molecular characteristics, optimal treatment modalities, and prognostic factors of adult T-LBL. Therefore, we summarized the existing studies to comprehensively discuss the above issues in this review. Genetic mutations of NOTCH1/FBXW7, PTEN, RAS, and KMT2D, together with abnormal activation of signaling pathways, such as the JAK-STAT signaling pathway were described. We also discussed the therapeutic modalities. Once diagnosed, adult T-LBL patients should receive intensive or pediatric acute lymphoblastic leukemia regimen and central nervous system prophylaxis as soon as possible, and cranial radiation-free protocols are appropriate. Mediastinal radiotherapy improves clinical outcomes, but adverse events are of concern. Hematopoietic stem cell transplantation may be considered for adult T-LBL patients with high-risk factors or those with relapsed/refractory disease. Besides, several novel prognostic models have been constructed, such as the 5-miRNAs-based classifier, 11-gene-based classifier, and 4-CpG-based classifier, which have presented significant prognostic value in adult T-LBL.

Comparison of Chemotherapy Combined With Chidamide Versus Chemotherapy in the Frontline Treatment for Peripheral T-Cell Lymphoma.

Background: Peripheral T-cell lymphoma (PTCL) is featured with a poor survival outcome. China has approved chidamide, an oral novel histone deacetylase inhibitor, for patients diagnosed with relapsed or refractory PTCL. Objective: We compared the benefit of traditional chemotherapy alone and a combination of chidamide and traditional chemotherapy against newly diagnosed PTCL. Prognostic factors related to progression and survival in patients diagnosed with untreated PTCL were also investigated. Methods: 104 patients with newly diagnosed PTCL were enrolled and divided into chemotherapy (ChT) group and chemotherapy combined with chidamide (ChT+C) group. Survival curves were plotted by the Kaplan-Meier method. Univariate and multivariate analysis were conducted with Log-rank test and Cox's proportional hazard regression. Subgroup analysis and interaction tests were conducted to evaluate factors associated with prognostic differences between ChT and ChT+C groups. Results: Compared with patients in ChT group, those in ChT+C group had superior progression-free survival (PFS) (p=0.047). However, there was no significantly statistical difference observed between the two groups in overall survival (OS) (p=0.212). High IPI scores have a negative relationship with survival. Multivariate analysis revealed that the type of frontline treatment regimen is an independent factor associated with PFS of PTCL patients (p=0.045). In the subgroup of patients with high international prognostic index scores (3-5), the HR value for PFS comparing ChT with ChT+C was 4.675. A test of interaction between IPI and treatment showed statistical significance (p = 0.037), implying that the benefits of ChT+C are higher for patients with high IPI scores. Conclusions: In summary, the combination of ChT and chidamide may provide a promising prospect for patients with newly diagnosed PTCL.

Incidence and Risk Factors of Cardiac Abnormalities in Patients with Idiopathic Scoliosis.

OBJECTIVE: We sought to investigate the incidence of cardiac abnormalities in patients with idiopathic scoliosis and identify risk factors related to cardiac abnormalities. METHODS: A cohort of 531 patients with idiopathic scoliosis requiring surgical treatment in our hospital from March 2009 to August 2017 were recorded. Clinical data including medical records, radiograph, and echocardiogram were collected. All patients were divided into groups: control, congenital heart disease (CHD), and other cardiac abnormalities (OCAs). The incidence and related factors for cardiac abnormalities were analyzed. RESULTS: The age of the study cohort was 17.8 ± 7.3 years. The average Cobb angle was 57.7 ± 16.5 degrees. Cardiac abnormalities were found in 149 (28.06%) patients, including 22 (4.14%) with CHD and 127 (23.92%) with OCAs. Atrial septal defect was the most common CHD with an incidence of 1.13% (6 of 531). Mitral valve prolapse was detected in 62 (11.68%) patients, which was the most prevalent OCA. Patients with CHD or OCAs weighed less as compared with patients without cardiac abnormalities. Low height was associated with CHD in patients with idiopathic scoliosis. Six patients with severe cardiac abnormalities must undergo cardiac intervention before scoliosis surgery. CONCLUSIONS: The overall incidence of cardiac abnormalities was 28.81% in patients with idiopathic scoliosis. An echocardiogram may be helpful as a preoperative examination for patients with idiopathic scoliosis before scoliosis surgery.

Coronal deformity angular ratio may serve as a valuable parameter to predict in-brace correction in patients with adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: In-brace correction (IBC) plays an important role in curve progression of patients with adolescent idiopathic scoliosis (AIS) under brace treatment. We evaluated the coronal deformity angular ratio (C-DAR) as a potential predictor of IBC. Based on our experience, we postulated that a high C-DAR may result in low IBC. This relationship had not been previously studied. PURPOSE: To evaluate the relationship of C-DAR and IBC in patients with AIS. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: A total of 119 patients with AIS treated with a Gensingen brace in our scoliosis center from July 2015 to October 2017 were included. OUTCOME MEASURES: In-brace correction. METHODS: Data were collected before and upon brace placement. Correlation analyses between study variables and IBC were performed. A linear regression model was established on the basis of C-DAR. RESULTS: At brace fitting, the average age was 12.62±1.16 (range, 10-15) years and mean major curve Cobb angle was 32.14±4.66° (range, 25-40°). Mean IBC was 59.62%±22.03% (range, 16.2-100%). IBC had significant correlation with C-DAR (r=-0.69; 95% confidence interval, -0.77 to -0.61; p<.001). IBC was not significantly correlated with age, sex, height, weight, BMI, menstrual status, or Risser sign. A simple linear regression model established that in-brace correction=115.4-10.7×C-DAR. CONCLUSIONS: C-DAR has strong negative correlation with IBC and may estimate the expected IBC. The usage of C-DAR may obviate the need for flexibility radiographs, such as supine or supine lateral bending radiographs.