Reirradiation with stereotactic body radiotherapy for primary or secondary lung malignancies: Tumor control probability and safety analyses.

BACKGROUND: Reirradiation with stereotactic body radiotherapy (SBRT) for patients with primary or secondary lung malignancies represents an appealing definitive approach, but its feasibility and safety are not well defined. The purpose of this study was to investigate the tumor control probability (TCP) and toxicity for patients receiving reirradiation with SBRT. PATIENTS AND METHODS: Eligible patients with recurrence of primary or secondary lung malignancies from our hospital were subjected to reirradiation with SBRT, and PubMed- and Embase-indexed articles were reviewed. The patient characteristics, pertinent SBRT dosimetric details, local tumor control, and toxicities were extracted. The logistic dose-response models were compared for TCP and overall survival (OS) in terms of the physical dose and three-, four-, and five-fraction equivalent doses. RESULTS: The data of 17 patients from our hospital and 195 patients extracted from 12 articles were summarized. Reirradiation with SBRT yielded 2-year estimates of 80% TCP for doses of 50.10 Gy, 55.85 Gy, and 60.54 Gy in three, four, and five fractions, respectively. The estimated TCP with common fractionation schemes were 50%, 60%, and 70% for 42.04 Gy, 47.44 Gy, and 53.32 Gy in five fractions, respectively. Similarly, the 2-year estimated OS was 50%, 60%, and 70% for 41.62 Gy, 46.88 Gy, and 52.55 Gy in five fractions, respectively. Central tumor localization may be associated with severe toxicity. CONCLUSIONS: Reirradiation with SBRT doses of 50-60 Gy in 3-5 fractions is feasible for appropriately selected patients with recurrence of peripheral primary or secondary lung malignancies, but should be carefully considered for centrally-located tumors due to potentially severe toxicity. Further studies are warranted for optimal dose/fractionation schedules and more accurate selection of patients suitable for reirradiation with SBRT.

Meta-Analysis of Circulating Endothelial Cells and Circulating Endothelial Progenitor Cells as Prognostic Factors in Lung Cancer.

BACKGROUND: The aim of this study was to analyze the prognostic implications of pretreatment circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients with lung cancer. MATERIALS AND METHODS: Relevant literature was identified using Medline and EMBASE. Patient clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC and CEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment of publication bias. RESULTS: A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled for the global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786], while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673 [5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted according to clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OS of patients with advanced lung cancer (stage III-IV). CONCLUSIONS: High counts of CECs seem to be associated only with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate with both worse PFS and OS.

Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo.

Aerobic glycolysis, a metabolic hallmark of cancer, is associated with radioresistance in non-small cell lung cancer (NSCLC). Pyruvate kinase M2 isoform (PKM2), a key regulator of glycolysis, is expressed exclusively in cancers. However, the impact of PKM2 silencing on the radiosensitivity of NSCLC has not been explored. Here, we show a plasmid of shRNA-PKM2 for expressing a short hairpin RNA targeting PKM2 (pshRNA-PKM2) and demonstrate that treatment with pshRNA-PKM2 effectively inhibits PKM2 expression in NSCLC cell lines and xenografts. Silencing of PKM2 expression enhanced ionizing radiation (IR)-induced apoptosis and autophagy in vitro and in vivo, accompanied by inhibiting AKT and PDK1 phosphorylation, but enhanced ERK and GSK3ß phosphorylation. These results demonstrated that knockdown of PKM2 expression enhances the radiosensitivity of NSCLC cell lines and xenografts as well as may aid in the design of new therapies for the treatment of NSCLC.

Psychosocial response and symptom burden for male smokers with lung cancer.

PURPOSE: Cigarette smoking causes many kinds of cancer, and it is more closely related with lung cancer, rather than other cancers. Smoking is the leading cause of lung cancer and ninety percent of the smokers are male in China, but there is little published data concerning the psychological responses in the male smokers with lung cancer and its influence on the symptom burden. The aim of the study was to verify the hypothesis that male smokers with lung cancer have more positive attitude and less symptom burden, comparing to male non-smokers. METHODS: A total of 194 men with cancer in West China Hospital, Sichuan, China, were assessed by self-administered questionnaire. Psychological response was measured by the Chinese version of Mini-Mental Adjustment to Cancer scale (Mini-MAC), and symptom burden was measured by the physical symptom distress scale from the Rotterdam Symptom Checklist (RSCL). RESULTS: We found that smokers with lung cancer got higher scores in positive attitude and a smaller symptom burden than non-smokers. Patients with education lower than high school got higher scores of positive attitude compared to college graduate patients (p=0.038). Smokers with lung cancer who knew the potential carcinogenicity of cigarette showed less negative emotions (p=0.011). The psychological response was not affected by age, clinical stage, cell type, smoking duration and amount. CONCLUSIONS: Male smokers with lung cancer have a more positive attitude and fewer symptoms, comparing to male non-smokers. Appropriate psychological intervention for non-smokers with lung cancer deserves more attention.

Effective response of the peritoneum microenvironment to peritoneal and systemic metastasis from colorectal carcinoma.

We here document discovery of a new and simple model of tumor seeding involving the mouse peritoneum. Irradiated tumor cells administered by i.p. injection provided effective vaccination against peritoneal carcinomatosis and distal metastasis with colorectal carcinomas. In flow cytometric analysis, CD4 and CD8+ T lymphocytes, macrophages and myeloid-derived suppressor cells (MDSCs), which are easy to obtain in the peritoneal cavity, were revealed to have significant differences between immunized and non-immunized mice and these contributed to antitumor responses. We also observed that both serum and peritoneal lavage fluid harvested from immunized mice showed the presence of CT26-specific autoantibodies. In addition, increase in level of TGF-ß1 and IL-10 in serum but a decrease of TGF-ß1 in peritoneum was found. Taken together, these findings may provide a new vaccine strategy for the prevention of peritoneal and even systemic metastasis of carcinomas through induction of an autoimmune response in the peritoneum.

Pretreatment thrombocytosis as a prognostic factor in women with gynecologic malignancies: a meta-analysis.

BACKGROUND: This study was performed to analyze the prognostic implications of pretreatment or preoperative thrombocytosis in women with gynecologic malignancies. MATERIAL AND METHODS: We surveyed 2 medical databases, PubMed and EMBASE, to identified all relevant studies. A total of 14 (n=3,490) that evaluated the link between thrombocytosis and 5-year survival were included. REVMAN version 5.1 was used for our analysis and publication bias was evaluated using the Begg's funnel plot and tested by STATA 11.0. Risk ratios (RRs) with 95% confidence intervals (CIs) generated by the random effect model were used to assess the strength of any association. RESULTS: 709(20.3%) of the 3,490 patients exhibited thrombocytosis (platelet counts >400?109/L) at primary diagnosis, and their mortality was 1.62-fold higher compared with the others (RR=1.62, 95%CI= [1.28- 2.05], p<0.0001). Thrombocytosis failed to have a stronger effect on the survival of advanced patients of stages III to IV in our study (n=478, RR=1.29, 95% CI= [1.13-1.48], p=0.0003), nor in women with cervical cancer in stage IB (n=1371, RR= 1.73, 95% CI= [1.71-2.58], p=0.007). In addition, when adjusted for different carcinoma, it was associated with worse prognosis for all except the ones with vulvar cancer (n=201, RR= 0.43, 95% CI= [0.14-1.29], p=0.13). CONCLUSIONS: This meta-analysis indicated that thrombocytosis might be associated with a worse prognosis for patients with gynecologic malignancies but without specificity or sensitivity for the ones in advanced stage. When adjusted for different gynecologic malignancies, it showed a significant effect on survival of all except vulvar cancers.

[Prognosis and its affecting factors in children with acute respiratory distress syndrome].

OBJECTIVE: To study the prognosis and the factors affecting the prognosis in children with acute respiratory distress syndrome (ARDS). METHODS: Seventy-eight children with ARDS were enrolled. The states of their survival within 30 days were followed-up. RESULTS: Of the 78 children with ARDS, 51 cases demised, 27 cases survived, with a 30-days survival rate of 35%. The average survival time was 14.4 days (median: 8 days). The peak of death appeared within 3 days after ARDS. There were significant differences in aspects of age, primary disease, percentage of neonatal hyaline membrane disease, pediatric critical illness score (PCIS), duration of mechanical ventilation, oxygenation index (PaO(2)/FiO(2)), white blood cell count and number of involved organs between the died and survived children (P<0.05 or 0.01). The Cox multiple factors analysis showed that the age (HR 3.924~3.938), primary disease (HR=1.817) and PCIS (HR=0.469) were the risk factors of death. CONCLUSIONS: The peak of death usually appears within 3 days after ARDS. Age, primary disease and PCIS are the independent factors of prognosis in children with ARDS.