[Radiation-Induced Heart Disease: Current Status and Challenges].

Being one of the major therapeutic measures for malignant tumors, radiation therapy, or radiotherapy, plays a particularly crucial role in the multidisciplinary integrated treatment of thoracic tumors. With the development in radiotherapy technology, the research focus has shifted from improving the overall survival of malignant tumor patients to reducing the incidence of radiation-related injuries. Currently, radiation-induced heart disease (RIHD) has become one of the leading non-cancer causes of death in thoracic tumor patients who have undergone radiotherapy, seriously affecting their quality of life and clinical prognosis. In recent years, there has been growing understanding of the pathogenesis of RIHD, and proposals have been made for some potential measures for the prevention and treatment of RIHD. Based on the clinical manifestations and pathological changes of RIHD that have been reported, we herein reviewed the biological mechanism and potential treatment options for RIHD. We also discussed existing challenges in the prevention and treatment of RIHD, intending to provide references for the prevention and treatment of RIHD.

Leptomeningeal metastasis after effective first-generation EGFR TKI treatment of advanced non-small cell lung cancer.

OBJECTIVE: To evaluate the influence of a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment on the clinical features of leptomeningeal metastasis (LM) progression and outcome in advanced non-small cell lung cancer (NSCLC) patients. METHODS: We retrospectively evaluated advanced NSCLC patients receiving effective first-generation EGFR TKI treatment (e.g., treatment > 6 months) at our institution between January 2008 and February 2014. Incidence, time to progression, and treatment outcome of LM were examined. RESULTS: In our cohort, 29/420 patients (6.9%) developed LM. Among the patients harboring L858R or deletion of exon 19 in EGFR, the incidence of LM was 10.7% (21/197) and 3.4% (7/203), respectively (P = 0.006). The median time to LM progression was 16.5 months (95% confidence interval (CI), 11.9-20.8). The median overall survival (OS) after LM diagnosis was 5.2 months (95% CI, 3.2-7.2). In a subgroup analysis, OS was improved in patients with performance status (PS) ≤ 2 vs. PS > 2 (14.2 months vs. 2.3 months, respectively; P < 0.001). OS was also improved among patients who received, rather than did not receive, anti-tumor treatment (6.0 months vs. 1.9 months, respectively; P < 0.001) or whole brain radiotherapy (WBRT) (6.0 months vs. 3.9 months, respectively; P = 0.038). Multivariate analysis indicated that WBRT is a good prognostic factor (P = 0.048), whereas best support care (P = 0.033) and PS > 2 (P = 0.034) were poor prognostic factors. CONCLUSION: A greater incidence of LM was observed in NSCLC patients harboring EGFR mutations after effective EGFR TKI treatment. In particular, the primary mutation, L858R, potentially predicts a higher risk of LM compared with deletion of exon 19. These results highlight the importance of determining mutation status when evaluating the biological behavior of LM in NSCLC patients who positively respond to EGFR TKI treatment.

Neutrophil-to-lymphocyte and aspartate-to-alanine aminotransferase ratios predict hepatocellular carcinoma prognosis after transarterial embolization.

The neutrophil-to-lymphocyte ratio (NLR) reflects the systematic inflammatory status, and the aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) is a biomarker of liver fibrosis and cirrhosis. These values can be conveniently obtained from routine blood tests; however, their combined clinical utility has not been extensively studied in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This study aimed to investigate the prognostic value of NLR-AAR in patients with unresectable HCC undergoing TACE. Data for 760 patients with newly diagnosed HCC were retrospectively evaluated. The NLR-AAR was calculated as follows: patients in whom both the NLR and AAR were elevated according to the receiver operating characteristic (ROC) curve analysis were assigned a score of 2; patients showing an elevation in one or neither of these indicators were assigned a score of 1 or 0, respectively. Univariate and multivariate analyses were performed to identify the clinicopathological variables associated with overall survival. An ROC curve was also generated and the area under the curve (AUC) was calculated to evaluate the discriminatory ability of each index at 1, 3, and 5 years of follow-up, as well as overall. The NLR-AAR consistently had a greater AUC value at 1 year (0.669), 3 years (0.667), and 5 years (0.671) post-TACE compared with either NLR or AAR alone. The median survival times of patients with a NLR-AAR of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 24.0-38.0), 15.0 (95% CI 11.2-18.8), and 5.0 (95% CI 4.0-5.9) months, respectively (P < .001). Multivariate analysis showed that the NLR-AAR, elevated total bilirubin level, and vascular invasion were independently associated with overall survival. NLR and AAR, when combined to produce an inflammation-based index and fibrosis score, is an independent marker of poor prognosis in patients with HCC receiving TACE.

Overexpression of miR-96 promotes cell proliferation by targeting FOXF2 in prostate cancer.

Prostate cancer (PC) is one of the most common cancers in males. MicroRNAs (miRNAs) are demonstrated to be involved in prostate cancer development and progression. Recently, miR-96 was identified to play a tumor promoting role in several tumors including PC, however, the underlying function of miR-96 in PC still need to be known. In the study, our results demonstrated that miR-96 was higher in prostate cancer tissues compared with adjacent normal tissues. Higher miR-96 was association with higher PSA level, lymph node metastasis, pathologic stage and distant metastasis in prostate cancer patients. Lose-of-function studies showed that down-regulated expression of miR-96 inhibited cell proliferation and cell cycle by regulating down-regulating CyclinA1, CDK2 and CDK4 expression in PC cells. Furthermore, we found that FOXF2 was a target of miR-96 in PC cells and miR-96 promoted cell proliferation by suppressing FOXF2 expression. Thus, these results showed that inhibition of miR-96 may be a target for prostate cancer treatment.

Chemotherapy-induced fatal hepatitis B virus reactivation in a small-cell lung cancer patient.

Hepatitis B virus (HBV) reactivation during chemotherapy is a major concern and is widely reported, particularly in association with hematological malignancies and lymphomas. While lung cancer ranks first in incidence and mortality worldwide, HBV reactivation has been largely overlooked in this disease. As regards small-cell lung cancer (SCLC), HBV reactivation has rarely been reported. We herein report the case of a hepatitis B surface antigen-seropositive SCLC patient in whom HBV was reactivated during the course of chemotherapy, despite preemptive use of lamivudine. The patient developed fulminant viral hepatitis and succumbed to liver failure. The aim of this report was to highlight the major but overlooked issue of HBV reactivation in SCLC, and suggest that agents more potent than lamivudine may be more efficacious in high-risk patients.

DNA repair gene polymorphisms and clinical outcome of patients with primary small cell carcinoma of the esophagus.

Polymorphisms in DNA repair genes impact on the synthesis of DNA repair proteins that are crucial to the repair of DNA damages induced by chemotherapy and radiotherapy. We retrospectively examined whether there was an association between the selected six single nucleotide polymorphisms (SNPs) of five DNA repair genes (PARP1-Val762Ala, XRCC1-Arg194Trp, XRCC1-Arg399Gln, XPC-Lys939Gln, BRCA1-Lys1183Arg, and BRCA2-Asn372His) and the clinical outcome of patients with primary small cell carcinoma of esophagus (SCCE), and it showed that the median progression-free survival (PFS) and the overall survival (OS) were 11.8 versus 9.7 months (P = 0.041) and 17.4 versus 14.8 months (P = 0.032) for patients carrying the variant allele (T/C + C/C) and the wild-type allele (T/T) of PARP1-Val762Ala polymorphism, respectively. However, no statistical significance was observed in the other five polymorphic loci (P > 0.05). When these six SNPs were combined, however, patients with at least three variant genotypes had significantly longer PFS and OS compared with those carrying less than three variant genotypes (P = 0.009 and P = 0.007, respectively). The presence of at least three polymorphic variants in certain DNA repair genes may impact on patient survival and could be a potential genomic predictor of clinical response to DNA-damaging treatment in SCCE patients.

Malignant fibrous histiocytoma like pleomorphic leiomyosarcoma with laryngeal cancer as a second primary neoplasm: a case report.

BACKGROUND: Leiomyosarcoma is one of the most common sarcomas arising in the soft tissue and somatic organs. Pleomorphic leiomyosarcoma (P-LMS) may be easily confused with a malignant fibrous histiocytoma (MFH) as both may share nonspecific morphologic features. It is reported that the larynx is the most common site for a second primary neoplasm (SPN) in a patient with a head and neck malignancy, although an SPN of the larynx following a P-LMS is extremely rare. CASE: A 57-year-old male initially underwent fine needle aspiration (FNA) of a soft tissue tumor (STS) located in the left upper arm. FNA showed the presence of clustered, large tumor cells with clear, eosinophilic and ill-defined cytoplasm and pleomorphic nuclei. A diagnosis of an undifferentiated malignant tumor was made. Histology showed the presence of MFH. This diagnosis was changed to P-LMS following a lung metastasis. A laryngeal biopsy 37 months after the initial biopsy was performed and showed squamous carcinoma. This squamous carcinoma was presumed to be an SPN. CONCLUSION: This is the first case report of a patient with a P-LMS who then developed laryngeal squamous carcinoma as an SPN.

Salvage treatment improved survival of patients with relapsed extranodal natural killer/t-cell lymphoma, nasal type.

PURPOSE: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type. METHODS AND MATERIALS: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone. RESULTS: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels. CONCLUSIONS: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.