Role of thoracic radiotherapy in extensive stage small cell lung cancer: a systemic review and meta-analysis.

BACKGROUND: The role of thoracic consolidation radiotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) remains controversial. This study aimed to evaluate the efficacy of thoracic radiotherapy (TRT) in these patients. METHODS: A systematic literature search was performed in PubMed, Embase, and the Cochrane library to identify qualified clinical studies. The hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were extracted, and toxicity of the TRT group versus non-TRT group was analyzed. RESULTS: A total of 12 studies were included in this meta-analysis, including 936 patients in the TRT group and 1,059 patients in the non-TRT group. The combined results showed that TRT significantly improved OS (HR =0.65; 95% CI: 0.55-0.77, P<0.00001), PFS (HR =0.64; 95% CI: 0.56-0.72, P<0.00001) and LRFS (HR =0.38, 95% CI: 0.26-0.53, P<0.00001). Subgroup analysis showed that OS benefits were observed in patients receiving sequential TRT (HR =0.67; 95% CI: 0.54-0.84, P=0.0006). The addition of TRT significantly improved OS in patients over 65 years of age (HR =0.55; 95% CI: 0.40-0.74, P=0.0001). For patients with only one organ metastasis, there was no significant difference in OS between the two groups (HR =0.61; 95% CI: 0.36-1.01, P=0.06). There was no statistical difference in hematologic toxicity (leukopenia, thrombocytopenia, anemia) and non-hematologic toxicity (nausea or vomiting) between the two groups. The incidence of grade ≥3 esophageal toxicity was 4.6% in the TRT group and 0% in the non-TRT group (P=0.0001). Grade ≥3 bronchopulmonary toxicity was 2.9% in the TRT group and 0.8% in the non-TRT group (P=0.02). CONCLUSIONS: TRT improves OS, PFS and LRFS in patients with ES-SCLC, with a low increase in esophageal and bronchopulmonary toxicity. More randomized controlled trials (RCTs) are expected to confirm our conclusions. PROSPERO REGISTRATION NUMBER: CRD42020190575.

Clinical outcomes and prognostic factors of stereotactic body radiation therapy combined with gemcitabine plus capecitabine for locally advanced unresectable pancreatic cancer.

PURPOSE: This study aimed to evaluate the clinical outcomes, toxicity, and prognostic factors of SBRT combined with gemcitabine plus capecitabine (GEM-CAP) in treating locally advanced pancreatic cancer (LAPC). METHODS: A total of 56 patients with LAPC treated with SBRT combined with GEM-CAP were reviewed from October 2010 to October 2016. The median total prescription dose at five fractions was 40 Gy (30-50 Gy). The patients were subjected to two cycles of GEM-CAP before SBRT. GEM-CAP chemotherapy was then offered for four cycles or until disease tolerance or progression. The primary endpoints included overall survival (OS) and progression-free survival (PFS). RESULTS: The median OS and PFS from the date of diagnosis was 19 (95% CI 14.6-23.4) and 12 months (95% CI 8.34-15.66), respectively. The 1-year and 2-year survival rates were 82.1% and 35.7%, whereas the 1-year and 2-year PFS rates were 48.2% and 14.3%, respectively. The median carbohydrate antigen 19-9-determined PFS time was 11 months (95% CI 5.77-16.24). Multivariate analysis demonstrated that tumor diameter, lymph node metastasis, pre-treatment CA19-9 level, and post-treatment CA19-9 decline were independent prognostic factors (p < 0.05). Acute toxicity was minimal, with two cases (3.6%) experiencing grade 3 duodenal obstruction. No adverse events greater than grade 3 occurred. In late toxicity, three patients (5.4%) developed grade 3 gastrointestinal toxicity and two (3.6%) suffered from perforation caused by grade 4 radiation enteritis and intestinal fistula. CONCLUSIONS: The combination of Cyberknife SBRT and GEM-CAP achieved excellent efficacy with acceptable toxicity for LAPC.

Aurora-a confers radioresistance in human hepatocellular carcinoma by activating NF-κB signaling pathway.

BACKGROUND: Radiotherapy failure is a significant clinical challenge due to the development of resistance in the course of treatment. Therefore, it is necessary to further study the radiation resistance mechanism of HCC. In our early study, we have showed that the expression of Aurora-A mRNA was upregulated in HCC tissue samples or cells, and Aurora-A promoted the malignant phenotype of HCC cells. However, the effect of Aurora-A on the development of HCC radioresistance is not well known. METHODS: In this study, colony formation assay, MTT assays, flow cytometry assays, RT-PCR assays, Western blot, and tumor xenografts experiments were used to identify Aurora-A promotes the radioresistance of HCC cells by decreasing IR-induced apoptosis in vitro and in vivo. Dual-luciferase reporter assay, MTT assays, flow cytometry assays, and Western blot assay were performed to show the interactions of Aurora-A and NF-κB. RESULTS: We established radioresistance HCC cell lines (HepG2-R) and found that Aurora-A was significantly upregulated in those radioresistant HCC cells in comparison with their parental HCC cells. Knockdown of Aurora-A increased radiosensitivity of radioresistant HCC cells both in vivo and in vitro by enhancing irradiation-induced apoptosis, while upregulation of Aurora-A decreased radiosensitivity by reducing irradiation-induced apoptosis of parental cells. In addition, we have showed that Aurora-A could promote the expression of nuclear IkappaB-alpha (IκBα) protein while enhancing the activity of NF-kappaB (κB), thereby promoted expression of NF-κB pathway downstream effectors, including proteins (Mcl-1, Bcl-2, PARP, and caspase-3), all of which are associated with apoptosis. CONCLUSIONS: Aurora-A reduces radiotherapy-induced apoptosis by activating NF-κB signaling, thereby contributing to HCC radioresistance. Our results provided the first evidence that Aurora-A was essential for radioresistance in HCC and targeting this molecular would be a potential strategy for radiosensitization in HCC.

[Cyberknife stereotactic body radiotherapy for liver metastases from prostate cancer].

OBJECTIVE: To investigate the effectiveness and adverse effects of Cyberknife stereotactic body radiotherapy (SBRT) on liver metastases from PCa. METHODS: From June 2009 to September 2016, we treated 20 cases of PCa liver metastases by Cyberknife SBRT, at a total dose of 36 (30－50) Gy, on 1－3 liver metastatic lesions, for 3－5 times, with a prescription isodose line of 70－92%. We assessed the therapeutic effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), calculated the survival and disease-control rates using the Kaplan-Meier method, and analyzed the adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events－Version 4.0 (CTCAE 4.0). RESULTS: Of all the cases treated, complete response (CR) was found in 8 (40.0%), partial response (PR) in 9 (45.0%), stable disease (SD) in 2 (10.0%), and progressive disease (PD) in 1 (5.0%), with a local control rate (CR+PR) of 85.0% and a disease-control rate (CR+PR+SD) of 95.0%. Among the 14 patients with elevated PSA, 10 (71.4%) showed a significant decrease after treatment. The median follow-up time was 17 months, the 1- and 2-year survival rates were 85.0% and 15.0%, respectively, and the median survival time of the 20 patients was 16.5 months (95% CI: 12.12－22.88). Cyberknife SBRT was well tolerated in all the patients, with only a few mild adverse events (mainly grades 1 and 2 but no 4 and 5) during the whole course of treatment. CONCLUSIONS: Cyberknife SBRT is safe and effective in the treatment of PCa liver metastases, with a high local control rate, and capable of reducing the PSA level and raising the long-term survival rate of the patients.

CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: A meta-analysis involving 10,947 subjects.

The above article, published in the Journal of Cellular and Molecular Medicine on 14 September 2016 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 19, pp. 2136-2142, has been retracted by agreement between the authors, the journal Editor in Chief, Stefan Constantinescu, and John Wiley & Sons Ltd. The retraction has been agreed due to unattributed overlap of the language used in the "Materials and method" and "Discussion" sections of this study and the following article published in Lung Cancer: "CYP2E1 Rsa I/Pst I polymorphism is associated with lung cancer risk among Asians" by Ping Zhan, Jing Wang, Yu Zhang, Li-Xin Qiu, Su-feng Zhao, Qian Qian, Shu-Zhen Wei, Li-Ke Yu and Yong Song, Volume 69, 2010, pages 19-25. REFERENCE Shen Z-T, Wu X-H, Li B, Shen J-S, Wang Z, Li J, Zhu X-X. CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: a meta-analysis involving 10,947 subjects. J Cell Mol Med. 2015;19:2136-2142. https://doi.org/10.1111/jcmm.12579.

Clinical outcomes and prognostic factors of stereotactic body radiation therapy for intrahepatic cholangiocarcinoma.

Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with intrahepatic cholangiocarcinoma (ICC) when surgical treatment cannot be applied. The CyberKnife® is a SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the clinical outcomes and prognostic factors for ICC patients receiving this treatment. Twenty-eight patients with ICC were enrolled in the present study. The median prescription dose was 45 Gy (range, 36-54 Gy), fractionated 3 to 5 times with a 70% to 92% isodose line. Local control, overall survival, progression-free survival and toxicity were studied. The median follow-up time was 16 months (3-42 months). Based on modified Response Evaluation and Criteria in Solid Tumors (mRECIST), response rate and disease control rate of SBRT in ICC were 46.4% (13/28) and 89.3% (25/28), respectively. Median overall survival was 15 months (95% CI, 7.22-22.78). 1- and 2-years survival rates were 57.1% and 32.1%, and 1- and 2- years Progression-free Survival rates were 50.0 % and 21.4 %. Multivariate analysis revealed that number of lesions (solitary vs. multiple nodules), CA19-9 levels (≤37 U/mL vs. 37-600/>600) and TNM stage (AJCC stage) were independent prognostic factors for ICC patients treated with SBRT. Toxicity was mostly transient and tolerable. No greater than grade 3 toxicity was observed. These results suggested that CyberKnife SBRT might be a good alternative treatment for unresectable ICC.

A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks-Gelman-Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

Prognostic Significance of microRNA-7 and its Roles in the Regulation of Cisplatin Resistance in Lung Adenocarcinoma.

BACKGROUND: Previously, microRNA (miR)-7 has been reported to function as a tumor suppressor in human cancers, but the correlations of miR-7 expression with prognosis and cisplatin (CDDP) resistance in lung adenocarcinoma (LA) are unclear. Here, our aim is to determine the prognostic significance of miR-7 and its roles in the regulation of CDDP resistance in LA. METHODS: Quantitative real-time PCR (qRT-PCR) assay was performed to determine miR-7 expression in 108 paired of LA tissues and analyze its correlations with clinicopathological factors of patients. The patient survival data were collected retrospectively by Kaplan-Meier analyses, and multivariate analysis was performed using the Cox proportional hazards model to determine the prognostic significance of miR-7 expression. The effects of miR-7 expression on the chemosensitivity of LA cells to CDDP and its possible mechanisms were evaluated by MTT, flow cytometry, Western blot and luciferase assays. RESULTS: It was observed that the relative expression level of miR-7 in LA tissues was significantly lower than that in the adjacent normal tissues and low miR-7 expression level was closely associated with poorer tumor differentiation, advanced pathological T-factor, higher incidence of lymph node metastasis and advanced p-TNM stage. Also, patients with low miR-7 expression showed a shorter overall survival than those with high miR-7 expression, and multivariate analysis indicated that status of miR-7 expression was an independent molecular biomarker for predicting the overall survival (OS) of LA patients. In addition, upregulation of miR-7 increases the sensitivity of LA cells to CDDP via induction of apoptosis by targeting Bcl-2. CONCLUSIONS: Our finding for the first time demonstrates that low miR-7 expression may be an independent poor prognostic factor and targeting miR-7 may be a potential strategy for the reversal of CDDP resistance in LA.

TGF-ß1 rs1982073 polymorphism contributes to radiation pneumonitis in lung cancer patients: a meta-analysis.

Transforming growth factor beta 1(TGF-ß1) polymorphism was associated with radiation pneumonitis (RP) susceptibility, but their results have been inconsistent. The PubMed and CNKI were searched for case-control studies published up to Januray 01, 2016 was Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta-analysis, we assessed eight publications involving 368 radiation pneumonitis cases and 855 controls of the association between TGF-ß1 T869C (rs1982073) and G915C (rs1800471) polymorphism and RP susceptibility. Our analysis suggested that TGF-ß1 T869C rs1982073 polymorphism was associated with lower RP risk for CT combined CC versus TT model (OR = 0.58, 95% CI = 0.43-0.77). However, for the G915C rs1800471 polymorphism, no association was found between the polymorphism and the susceptibility to RP in GC combined CC versus GG model (OR = 0.82, 95% CI = 0.50-1.35). These results from the meta-analysis suggest that T869C rs1982073 polymorphism of TGF-ß1 may be associated with RP risk, and there may be no association between G915C polymorphism and RP risk.

CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: a meta-analysis involving 10,947 subjects.

Many studies have examined the association between the CYP2E1 Rsa Ι/Pst Ι (rs3813867) polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. The PubMed and CNKI database was searched for case-control studies published up to October 2013. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta-analysis, we assessed 23 published studies involving comprising 4727 lung cancer cases and 6220 controls of the association between CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer risk. For the homozygote c2/c2 and c2 allele carriers (c1/c2 + c2/c2), the pooled ORs for all studies were 0.73(95% CI = 0.62-0.84; P = 0.005 for heterogeneity) and 0.84 (95% CI = 0.77-0.92; P = 0.001 for heterogeneity) when compared with the homozygous wild-type genotype (c1/c1). In the stratified analysis by ethnicity, the same significantly risks were found among Asians and mixed population for both the c2 allele carriers and homozygote c2/c2. However, no significant associations were found in Caucasian population all genetic models. This updated meta-analysis suggests that CYP2E1 Rsa Ι/Pst Ι c2 allele is a decreased risk factor for the developing lung cancer among Asians and mixed population.

Clinical outcomes of cyberknife stereotactic radiosurgery for lung metastases.

BACKGROUND: Cyberknife stereotactic radiosurgery is an emerging noninvasive technique for treating oligometastatic cancer. The aim of this study is to evaluate the efficacy and tolerability of cyberknife for the treatment of patients with lung metastases. MATERIALS AND METHODS: A total of 134 lung metastases in 95 patients were treated with cyberknife in the radiotherapy center of our hospital from March 2009 to March 2013. The number of lung metastases per patient ranged from one to four (single lesions in 63 patients, 66.3%). The average tumor volume was 14.6 cm(3) and the prescribed radiation dosage ranged from 30  to 60 Gy, fractionated one to five times with a 60% to 88% isodose line. The primary end point was local control (LC); secondary end points were survival and toxicity. RESULTS: The median follow-up was 17 months (ranging from 4 to 46 months). The 1-year LC rate was 97.6%, the 2-year LC rate was 90.6%, and the 3-year LC rate was 87.0%. The median survival time was 38.0 months and the median progression-free survival (PFS) time was 14.0 months. The 2-year PFS rate was 29.0% and the overall survival (OS) rate was 61.3%. No grade 4 or higher toxicity was encountered. CONCLUSIONS: Cyberknife is safe and effective treatment for patients with lung metastases.

Clinical outcomes of CyberKnife stereotactic body radiotherapy for peripheral stage I non-small cell lung cancer.

The aim of this study was to evaluate the clinical outcome of CyberKnife stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). Fifty patients with peripheral stage I NSCLC who refused surgery or were medically inoperable were treated with 48-60 Gy (median dose: 57 Gy) in three divided doses. Histopathology was available in 86% of patients. Thirty patients had a T1 tumor, and 20 patients had T2 tumors. More than 95% of the target volume was covered by the 72% isodose surface. Fiducials were implanted in or near the tumors in all patients to track tumor movement and breathing patterns. The median follow-up time was 35 months (3-45 months). Based on computed tomography scans, 40 patients achieved complete remission, six patients achieved partial remission, two patients exhibited stable disease, and two patients had progressive disease. The local control rate (CR + PR) was 92%, and the 2-year disease control rate (CR + PR + SD) was 96%. Overall survival for the whole group was 86% at 1 year and 74% at 2 years. Grade III toxicity occurred in two patients (4%) after marker placement. Treatment-related late grade III toxicity occurred in five patients (10%). Toxicities greater than grade III were not observed. CyberKnife SBRT achieves a high rate of local control and long-term curative effect with acceptable toxicity for patients with inoperable stage I NSCLC. However, long-term follow-up is necessary to evaluate survival and late toxicity.

CyberKnife Treatment for Kaposiform Hemangioendothelioma of the Ilium in an adult: case report and review of the literature.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that mainly affects infants. KHE rarely develops in adolescents and adults. These tumors tend to be locally invasive, but are not known to produce distant metastases. Numerous treatment modalities are available for KHE, but the optimal therapy is unknown. CASE REPORT: A 51-year-old woman was diagnosed with KHE of the ilium in September 2005. The lesion recurred within 5 years of local excision, and was subsequently treated with CyberKnife. Within 1 month of CyberKnife therapy, pain intensity was significantly reduced and the patient's quality of life was significantly improved. Since January 2011, she has remained pain-free and has had no signs of recurrence or metastasis for more than 2 years following CyberKnife therapy. CONCLUSION: We report the first CyberKnife treatment of an adult with KHE of the bone without accompanying cutaneous changes and Kasabach-Merritt syndrome. CyberKnife treatment could be a useful temporizing measure for bone KHE.

CyberKnife radiotherapy for malignant fibrous histiocytoma of the chest wall: A case report and review of the literature.

Malignant fibrous histiocytoma (MFH) is the most common type of soft tissue sarcoma, but rarely originates in the chest wall. Surgical resection is considered to be the most reliable treatment, however, no consensus has been reached concerning the best treatment for unresectable MFH. The current study presents the case of a 77-year-old male with MFH of the chest wall. The patient developed a painless mass and intermittent fever over a four-month period. A computed tomography scan demonstrated a large inhomogeneous lesion in the right chest wall, which was subsequently diagnosed via biopsy as a MFH. Since the tumor was an unresectable mass, CyberKnife® radiotherapy was conducted. Following the treatment, a marked reduction in the tumor size was observed with a tolerable level of toxicity. The sequencing analysis also revealed an in-frame deletion (delE746-A750) in exon 19 of the epidermal growth factor receptor gene. Based on this result, gefitinib was administered to the patient at a dose of 250 mg/day.

Nedaplatin concurrent with three-dimensional conformal radiotherapy for treatment of locally advanced esophageal carcinoma.

AIM: To evaluate the efficacy and toxicity of nedaplatin (NDP) concurrent with radiotherapy in the treatment of locally advanced esophageal carcinoma. METHODS: Sixty-eight patients with locally advanced esophageal carcinoma were randomized into either a NDP group (n = 34) or a cisplatin (DDP) group (n = 34). The NDP group received NDP 80-100 mg/m² iv on day 1 + leucovorin (CF) 100 mg/m² iv on days 1-5 + 5-fluorouracil (5-FU) 500 mg/m² iv on days 1-5. The DDP group received DDP 30 mg/m² iv on days 1-3 + CF 100 mg/m² on days 1-5 + 5-FU 500 mg/m² iv on days 1-5. The treatment was repeated every 4 wk in both groups. Concurrent radiotherapy [60-66 Gy/(30-33 f)/(6-7 wk)] was given during chemotherapy. RESULTS: There was no significant difference in the short-term response rate between the NDP group and DDP group (90.9% vs 81.3%, P = 0.528). Although the 1- and 2-year survival rates were higher in the NDP group than in the DDP group (75.8% vs 68.8%, 57.6% vs 50.0%), the difference in the overall survival rate was not statistically significant between the two groups (P = 0.540). The incidences of nausea, vomiting and nephrotoxicity were significantly lower in the NDP group than in the DDP group (17.6% vs 50.0%, P = 0.031; 11.8% vs 47.1%, P = 0.016; 8.8% vs 38.2%, P = 0.039). There was no significant difference in the incidence of myelosuppression, radiation-induced esophagitis or radiation-induced pneumonia between the two groups. CONCLUSION: NDP-based concurrent chemoradiotherapy is effective and well-tolerated in patients with locally advanced esophageal carcinoma. NDP-based regimen has comparable efficacy to DDP-based regimen but is associated with lower incidences of gastrointestinal and renal toxicity.

Preliminary efficacy of CyberKnife radiosurgery for locally advanced pancreatic cancer.

BACKGROUND AND OBJECTIVE: CybeKnife is a newly developed technology in the field of stereotactic radiosurgery/radiotherapy (SRS/SRT). Compared with conventional SRS/SRT, there are many advantages for CyberKnife in terms of treating tumors that move with respiration, being real-time image-guidance, frameless, high accurateness, and so on. Recently, it has been used to treat different types of malignant carcinoma including intracranial and caudomedial tumors. This study was designed to evaluate the short-term efficacy and toxicity of the CyberKnife radiotherapy for locally advanced pancreatic cancer. METHODS: A total of 20 patients with locally advanced (stage II-III) pancreatic cancer treated with CyberKnife were recruited between April 2009 and December 2009. Of 20 patients, 13 were with cancer located at the pancreatic head and 7 were located at the pancreatic body and tail. The planning target volume (PTV) was defined as gross tumor volume (GTV) plus 2-3 mm, and more than 95% PTV should be covered by 75% isodose surface. The median of PTV was 47 cm³ (26-64 cm³). The median total prescription dose was 40 Gy (32-55 Gy) at 3-6 fractions. During treatment delivery, X-Sight Spine Tracking System was used in 5 patients to track movement of the tumor. Other 15 patients were implanted fiducials in the tumors to track movement of the tumor and patient breathing patterns. RESULTS: The median follow-up time was 7 months (3-11 months). All patients had finished the treatment and 19 were alive by the last follow-up. Slight fatigue was the most common complain. Evaluated by CT scan, 6 were complete response, 9 were partial response, 3 were stable disease, and 1 was progression; 1 was dead. There were 6 patients with grade I granulocytopenia, 7 with grade I nausea, and 5 with grade II vomiting. CONCLUSIONS: The CyberKnife radiosurgery for the locally advanced pancreatic cancer shows a high rate of local control and minimal toxicity. Long-term follow-up is necessary to evaluate the survival and late toxicity.