Preoperative to postoperative change in neutrophil-to-lymphocyte ratio predict survival in colorectal cancer patients.

AIM: To evaluate the prognostic value of preoperative to postoperative neutrophil-to-lymphocyte ratio changes (ΔNLR) in patients undergoing surgical resection for colorectal cancer. PATIENTS & METHODS: Data of 135 such patients managed at the Shandong Cancer Hospital and Institute were retrospectively analyzed. Clinicopathologic factors, overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier curves and Cox regression models. RESULTS: In the multivariate analysis, preoperative NLR (p = 0.002) and ΔNLR (p = 0.037) independently predicted OS, but preoperative NLR (p = 0.141) and ΔNLR (p = 0.297) were not significant prognosticators for DFS. CONCLUSION: Our results demonstrated the prognostic value of the ΔNLR in predicting OS in patients undergoing surgical resection for colorectal cancer. However, ΔNLR could not predict DFS.

BTG2 overexpression increases the radiosensitivity of breast cancer cells in vitro and in vivo.

Antiproliferative gene B-cell translocation gene, member 2 (BTG2) is a member of the BTG/TOB antiproliferative gene family. In this study, we investigated the effect of BTG2 gene overexpression on the radiosensitivity of breast cancer cells in vitro and in vivo. Results show that in human breast cancer cell line MCF-7 stably overexpressing BTG2 gene, cell sensitivity to ionizing radiation increased. The MCF-7-BTG2 cells were more susceptible to radiation-caused apoptosis with decreased cyclin B1, cyclin D1, Ku70, FEN-1, and XRCC1 protein expression as well as increased BAX protein expression. The findings indicate for the first time that BTG2 can improve the radiosensitivity of breast cancer cells by affecting cell cycle distribution, enhancing radiation-induced apoptosis, and inhibiting DNA repair-related protein expression.

Imaging of proliferation with 18F-FLT PET/CT versus 18F-FDG PET/CT in non-small-cell lung cancer.

PURPOSE: To compare the diagnostic efficacies of (18)F-FLT and (18)F-FDG PET/CT in non-small-cell lung cancer (NSCLC), focusing on the correlation between FLT and FDG tumour uptake and tumour cell proliferation as indicated by the cyclin D1 labelling index. METHODS: A total of 31 patients with NSCLC underwent FLT and FDG PET/CT scanning followed by surgery. PET/CT images were compared with the pathology. Tumour cell proliferation was assessed by cyclin D1 immunohistochemistry. RESULTS: The sensitivities of FLT and FDG PET/CT for the primary lesion were 74% and 94%, respectively (p=0.031). For N staging, 77% patients were correctly staged, 6% overstaged, 16% understaged by FLT, while the values for FDG were 77%, 16% and 6%, respectively. The sensitivity, specificity, accuracy, and positive predictive value with FLT for lymph nodes were 65%, 98%, 93% and 89%, respectively, and 85%, 84%, 84% and 52% with FDG (p<0.01).Tumour SUV of FLT was significantly correlated with the cyclin D1 labelling index (r=0.644; p<0.01), but the SUV of FDG was not significantly correlated (r=0.293; p>0.05). CONCLUSION: In terms of N staging, FLT PET/CT resulted in understaging of more patients but overstaging of fewer patients, and for regional lymph nodes showed better specificity, accuracy and positive predictive value than FDG PET/CT in NSCLC. Tumour FLT uptake was correlated with tumour cell proliferation as indicated by the cyclin D1 labelling index, suggesting that further studies are needed to evaluate the use of FLT PET/CT for the assessment of therapy response to anticancer drugs.

[Value of 18F-FETNIM PET-CT for detection of tumor hypoxia in non-small-cell lung cancer].

OBJECTIVE: To assess the feasibility of [(18)F]fluoroerythronitroimidazole ((18)F-FETNIM) with integrated positron emission tomography and computed tomography (PET-CT) imaging in detection of hypoxia in non-small-cell lung cancer (NSCLC) patients. METHODS: Forty-two patients with newly diagnosed NSCLC underwent (18)F-FETNIM PET-CT before treatment. Nineteen patients rested for approximately 120 minutes before undergoing PET-CT, 23 patients underwent 2 sequential PET-CT scans at 60 minutes and 120 minutes after intravenous injection (18)F-FETNIM. (18)F-FETNIM uptake was quantified by calculating the maximum standardized uptake value in the tumor (SUVmax-T) and contralateral normal lung tissue (SUVmax-N). Regions of interest (ROIs) were drawn in the tumor and contralateral position and the radioactivity ratio of tumor to normal (T/N) was calculated. RESULTS: SUVmax-T (2.43 +/- 1.34) was significantly higher than SUVmax-N (0.87 +/- 0.46, P < 0.001) at 120 min. SUVmax-T (2.80 +/- 1.09) and SUVmax-N (1.16 +/- 0.56) at 60 min were significantly higher than SUVmax-T (2.61 +/- 1.10) and SUVmax-N (P < 0.01) at 120 min. T/N (2.56 +/- 0.71) at 60 min was higher than that at 120 min (2.48 +/- 0.60), but the difference between them was not significant (P = 0.324). CONCLUSION: Our results indicate that (18)F-FETNIM PET-CT may be a useful tool for evaluating hypoxia and may be a means to target specifically tumor cells resistant to conventional treatment before and during ongoing therapy in NSCLC.

Potential immune escape mechanisms underlying the distinct clinical outcome of immune checkpoint blockades in small cell lung cancer.

Small cell lung cancer (SCLC) is one of the deadliest cancer types in the world. Despite the high response rate to frontline platinum-containing doublets, relapse is inevitable for the majority of patients and the prognosis is poor. Topotecan, which has limited efficacy, has remained the standard second-line therapy for approximately three decades. Although SCLC has a high mutation burden, the clinical efficacy of immune checkpoint blockades (ICBs) in SCLC is far less pronounced than that in non-small cell lung cancer (NSCLC). Only atezolizumab in combination with chemotherapy improved overall survival over chemotherapy alone in the phase III CheckMate 133 trial and has recently received FDA approval as first-line therapy. Most studies concerning ICBs in SCLC are limited to early-phase studies and found that ICBs were not superior to traditional chemotherapy. Why is there such a large difference between SCLC and NSCLC? In this review, comparative analyses of previous studies indicate that SCLC is even more immunodeficient than NSCLC and the potential immune escape mechanisms in SCLC may involve the low expression of PD-L1 and the downregulation of major histocompability complex (MHC) molecules and regulatory chemokines. In consideration of these immune dysfunctions, we speculate that chemotherapy and radiotherapy prior to immunotherapy, the combination of ICBs with antiangiogenic treatment, and selecting tumor mutation burden in combination with PD-L1 expression as biomarkers could be promising strategies to improve the clinical efficacy of immunotherapy for SCLC.

The potential mechanism, recognition and clinical significance of tumor pseudoprogression after immunotherapy.

As immunotherapy has gained increasing interest as a new foundation for cancer therapy, some atypical response patterns, such as pseudoprogression and hyperprogression, have garnered the attention of physicians. Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear, followed by a decrease in tumor burden; this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression. Accurately recognizing pseudoprogression is also a challenge for physicians. Because of the extensive attention on pseudoprogression, significant progress has been made. Some new criteria for immunotherapy, such as irRC, iRECIST and imRECIST, were proposed to accurately evaluate the response to immunotherapy. Many new detection indexes, such as ctDNA and IL-8, have also been used to identify pseudoprogression. In this review, the definition, evaluation criteria, mechanism, monitoring, management and prognosis of pseudoprogression are summarized, and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed; these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.

Whole brain radiation therapy does not improve the overall survival of EGFR-mutant NSCLC patients with leptomeningeal metastasis.

BACKGROUND: Leptomeningeal metastasis (LM) is a devastating and terminal complication of advanced non-small-cell lung cancer (NSCLC), especially in patients harboring epidermal growth factor receptor (EGFR) mutations. The role of whole brain radiation therapy (WBRT) in the treatment of EGFR-mutant NSCLC patients with LM is not conclusive. Therefore, we conducted a retrospective study to evaluate the therapeutic effect of WBRT in this setting. METHODS: EGFR-mutant NSCLC patients with LM, who had previously received treatment at the Shandong Cancer Hospital and Institute from July 2014 to March 2018 were reviewed retrospectively. LM was diagnosed by positive CSF cytology and/or leptomeningeal-enhanced magnetic resonance imaging (MRI). Survival was estimated using the Kaplan-Meier method. RESULTS: In total, 51 EGFR-mutated NSCLC patients with LM were eligible for analysis, subdivided into 26 in the WBRT group and 25 in the non-WBRT group. No significant differences were observed in intracranial ORR (15.4% vs. 16%, p = 0.952) and DCR (34.7% vs. 28%, p = 0.611) between the two groups. The median iPFSLM and OSLM for the entire cohort were 3.3 months (95% CI: 2.77-3.83) and 12.6 months (95% CI: 9.66-15.54), respectively. No difference in iPFSLM was observed between the WBRT and non-WBRT groups (median 3.9 vs. 2.8 months; HR = 0.506, p = 0.052). The median OSLM was 13.6 months in the WBRT group, compared with 5.7 months in the non-WBRT group (HR = 0.454, p = 0.022). Multivariate analyses of OSLM showed that KPS ≥ 80 at the time of LM diagnosis (HR = 0.428, 95% CI: 0.19-0.94; p = 0.034) and the administration of EGFR-TKIs (HR = 0.258, 95% CI: 0.11-0.58; p = 0.001) were independent predictors of survival, but WBRT (HR = 0.49, 95% CI: 0.24-1.01; p = 0.54) was not. Toxicities associated with WBRT or other treatment were rare. CONCLUSION: For EGFR-mutated NSCLC patients with LM, WBRT did not improve intracranial treatment response and survival statistically.

Promoter hypermethylation-mediated down-regulation of CXCL12 in human astrocytoma.

It has recently been demonstrated that CXCL12 is absent in colonic carcinoma, and hypermethylation of CXCL12 contributes to CXCL12/CXCR4 signaling in carcinoma metastasis. However, the role of CXCL12/CXCR4 axis, especially CXCL12, in the regulation of tumor invasiveness is largely still unknown. Using real-time quantitative RT-PCR assays, we observed that CXCR4 expression increased with increasing WHO grade in astrocytoma, suggesting that CXCR4 may be a marker of aggressive biological behavior of astrocytoma. Methylation of CXCL12 was detected in 34.2% (26/76) of astrocytomas by methylation-specific PCR. Epigenetic inactivation of CXCL12 was implicated mainly in low-grade astrocytomas, via DNA hypermethylation by DNMT1, -3A, and -3B; 21.1% (16/76) of the astrocytomas showed reduced or lack of CXCL12 expression, in line with epigenetic silencing of gene transcripts. However, it is interesting to note that 61.8% (47/76) of tumors, mainly high-grade astrocytomas, displayed elevated transcription of CXCL12. The expression levels of CXCL12 mRNA in glioblastomas (WHO grade IV) were significantly higher than in normal brain tissues. In summary, our data show that CXCL12 promoter hypermethylation is an early event in astrocytoma development. However, the high expressions of CXCR4 and CXCL12 in glioblastomas, the more invasive astrocytomas, suggest a different role of CXCL12/CXCR4 signaling axis in astrocytoma progression.

Prognostic Value of Metabolic Parameters of Metastatic Lymph Nodes on 18F-FDG PET/CT in Patients With Limited-stage Small-cell Lung Cancer With Lymph Node Involvement.

INTRODUCTION: We assessed the prognostic value of the metabolic parameters of different lesions, including primary tumors and metastatic lymph nodes (LNs), measured by fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/computed tomography in patients with limited-stage small-cell lung cancer (LS-SCLC) with LN metastasis. MATERIALS AND METHODS: The present retrospective study included 46 patients with clinical stage II-III N1-N2 LS-SCLC who had undergone pretreatment fluorine-18 fluorodeoxyglucose PET/computed tomography scanning from January 2011 to December 2014. All patients underwent complete first-line therapy (concurrent chemoradiotherapy and prophylactic cranial irradiation). The metabolic parameters, including maximal standardized uptake value, mean standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values of the PTs and metastatic LNs were measured on PET. Kaplan-Meier survival curves were used for evaluation of progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors. RESULTS: The median OS and PFS were 25.9 months (range, 8.2-63.5 months) and 21 months (range, 6.4-55.3 months), respectively. Univariate analysis demonstrated that the Eastern Cooperative Oncology Group performance status, N1 station involvement, subcarinal LN metastasis, LN MTV, LN TLG, sum of the MTV, and summary of the TLG were significant predictive factors (P < .05). The Eastern Cooperative Oncology Group performance status, subcarinal nodal metastasis, LN MTV, and LN TLG were independent predictive factors of PFS and OS on multivariate analysis. CONCLUSION: The metabolic parameters of metastatic LNs, other than lung lesions, are independent prognostic factors in patients with LS-SCLC with LN metastasis. These parameters could further stratify the prognosis of these patients, and these findings might provide functional imaging evidence for the future study of the mechanisms of metastasis.

[Preliminary study of 18F-FDG PET-CT in defining lymph node radiation target volume for non-small-cell lung cancer patients].

OBJECTIVE: To investigate the value of 18F-FDG PET-CT in detecting metastatic lymph node and radiation planning for patient with non-small-cell lung cancer (NSCLC). METHODS: The data of 58 NSCLC patients were retrospectively analyzed. Preoperatively, Both 18F-FDG PET-CT and CT scan were performed for all patients. Blinded interpretation of these images was then carried out. The gross tumor volume defined by radiation oncologist based on imaging results of either PET-CT or CT alone was compared with pathological results eventually. RESULTS: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of detecting metastatic lymph node in the mediastinum was 56.0%, 54.2%, 54.8%, 38.9%, 70.3% by CT alone, and 88.0%, 85.4%, 86.3%, 75.9%, 93.2% by PET-CT, respectively. There was a statisticalty significant difference between two methods(P < 0.05). However, statisticalty no significant difference in detecting hilar lymph nodes was observed. The radiation target volume defined by CT was identical to that by PET-CT in 31(53.5%) cases, but changed in the other 27 (46.5%) cases when 18F-FDG PET data was added. The accuracy was 75.9% in detecting metastatic lymph nodes in the radiation target volume defined by PET-CT, while it was much lower by CT alone (48.3%) with a statistically significant difference between two methods (P < 0.05). CONCLUSION: 18F-FDG PET-CT is more accurate than CT alone in assessment of mediastinal lymph nodes for NSCLC patients. It may be recommended as a method in defining the radiation target volume.

The role of metabolic tumor volume (MTV) measured by [18F] FDG PET/CT in predicting EGFR gene mutation status in non-small cell lung cancer.

Many noninvasive methods have been explored to determine the mutation status of the epidermal growth factor receptor (EGFR) gene, which is important for individualized treatment of non-small cell lung cancer (NSCLC). We evaluated whether metabolic tumor volume (MTV), a parameter measured by [18F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) might help predict EGFR mutation status in NSCLC. Overall, 87 patients who underwent EGFR genotyping and pretreatment PET/CT between January 2013 and September 2016 were reviewed. Clinicopathologic characteristics and metabolic parameters including MTV were evaluated. Univariate and multivariate analyses were used to assess the independent variables that predict mutation status to create prediction models. Forty-one patients (41/87) were identified as having EGFR mutations. The multivariate analysis showed that patients with lower MTV (MTV≤11.0 cm3, p=0.001) who were non-smokers (p=0.037) and had a peripheral tumor location (p=0.033) were more likely to have EGFR mutations. Prediction models using these criteria for EGFR mutation yielded a high AUC (0.805, 95% CI 0.712-0.899), which suggests that the analysis had good discrimination. In conclusion, NSCLC patients with EGFR mutations showed significantly lower MTV than patients with wild-type EGFR. Prediction models based on MTV and clinicopathologic characteristics could provide more information for the identification of EGFR mutations.

The postoperative neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after the complete resection of stage I non-small cell lung cancer.

PURPOSE: Although numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent complete resection of stage I NSCLC. The aim of this retrospective study was to evaluate the prognostic significance of postoperative NLR and ΔNLR in 123 patients with stage I NSCLC. PATIENTS AND METHODS: This retrospective study included preoperative and postoperative data of 123 patients who underwent surgical resection for stage I NSCLC. The relationship between disease-free survival (DFS), overall survival (OS), and clinicopathological factors, including NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and their changes, was analyzed using both univariate Kaplan-Meier and multivariate Cox regression methods. RESULTS: The 5-year DFS and OS rates in our cohort were 60.16% and 67.48%, respectively. Univariate analysis revealed that age (P=0.045), smoking status (P=0.033), preoperative NLR (P=0.032), postoperative NLR (P<0.001), ΔNLR (P=0.004), and change in LMR (ΔLMR) (P=0.025) were significant predictors of DFS and that age (P=0.039), smoking status (P=0.042), postoperative NLR (P<0.001), ΔNLR (P=0.004), and ΔLMR (P=0.011) were independent predictors of OS. Multivariate analysis confirmed that postoperative NLR (hazard ratio [HR] =2.435, P=0.001) and ΔNLR (HR =2.103, P=0.012) were independent predictors of DFS and that postoperative NLR (HR =2.747, P=0.001) and ΔNLR (HR =2.052, P=0.018) were significant prognostic factors of OS. CONCLUSION: Our study reported for the first time that postoperative NLR and ΔNLR - but not preoperative NLR - were independent prognostic factors of DFS and OS in patients with stage I NSCLC who underwent complete resection. This easily available biomarker might be helpful in individual risk assessment.

PD-1/PD-L1 blockades in non-small-cell lung cancer therapy.

Lung cancer is the leading cause of cancer death in males and the second leading cause of death in females worldwide. Non-small-cell lung cancer (NSCLC) is the main pathological type of lung cancer, and most newly diagnosed NSCLC patients cannot undergo surgery because the disease is already locally advanced or metastatic. Despite chemoradiotherapy and targeted therapy improving clinical outcomes, overall survival remains poor. Immune checkpoint blockade, especially blockade of programmed death-1 (PD-1) receptor and its ligand PD-L1, achieved robust responses and improved survival for patients with locally advanced/metastatic NSCLC in preclinical and clinical studies. However, with regard to PD-1/PD-L1 checkpoint blockade as monotherapy or in combination with other antitumor therapies, such as chemotherapy, radiotherapy (including conventional irradiation and stereotactic body radiotherapy), and target therapy, there are still many unknowns in treating patients with NSCLC. Despite this limited understanding, checkpoint blockade as a novel therapeutic approach may change the treatment paradigm of NSCLC in the future. Here we review the main results from completed and ongoing studies to investigate the feasibility of PD-1/PD-L1 inhibitors, as monotherapy or combinatorial agents in patients with locally advanced and metastatic NSCLC, and explore optimal strategy in such patients.

Risk factors of brain metastasis during the course of EGFR-TKIs therapy for patients with EGFR-mutated advanced lung adenocarcinoma.

Controversial value of prophylactic cranial irradiation (PCI) in NSCLC in terms of survival benefit prompted us to explore the possible risk factors for brain metastasis (BM) during the course of EGFR-TKIs therapy from EGFR-mutated advanced lung adenocarcinoma and identify the potential population most likely to benefit from PCI, because BM remains a therapeutically challenging issue. We retrospectively reviewed the records of 134 patients with EGFR-mutated advanced lung adenocarcinoma between 2008 and 2012. The cumulative incidence of BM was calculated by the Kaplan-Meier method, and Multivariate Cox regression analysis was used to assess the independent risk factors for BM. Thirty-four patients (34/134, 25.4%) developed BM during the course of EGFR-TKIs therapy. Moreover, the Multivariate analysis indicated that age ≤ 53 years (HR: 2.751, 95 % CI: 1.326-5.707; p = 0.007), serum carcinoembryonic antigen (CEA) ≥ 23 ng/mL (HR: 3.197, 95 % CI: 1.512-6.758; p = 0.002) and EGFR exon 21 point mutations (HR: 2.769, 95 % CI: 1.355-5.659; p= 0.005) were the independent high-risk factors for developing BM, which could offer important insights into the individualized treatment. Further studies are warranted to validate our findings.

Predictive value of 18F-fluorodeoxyglucose positron emission tomography - computed tomography compared to postoperative pathological findings for patients with non-small-cell lung cancer.

This study was conducted to investigate the predictive value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) in patients with non-small-cell lung cancer (NSCLC), compared to that of postoperative pathological findings, for T and N staging and the associations of the metabolic parameters of the primary tumor with histological type and differentiation. The preoperative contrast-enhanced CT and 18F-FDG PET-CT and postoperative pathological findings of 112 NSCLC patients treated with lobectomy or pneumonectomy combined with systematic mediastinal lymphadenectomy were retrospectively reviewed. Compared to the postoperative pathological findings, the effect of contrast-enhanced CT and 18F-FDG PET-CT on T and N staging were evaluated. The metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) of the primary tumor were measured. The associations between these metabolic parameters and histological type and differentiation were also evaluated. The differences in the accuracy in overall staging and T staging between PET-CT and contrast-enhanced CT were significant (91.1 vs. 69.6%, P=0.000; and 92.9 vs. 76.8%, P=0.000, respectively). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of regional lymph node metastasis detection were 91.7, 93.0, 86.5, 95.8 and 92.6%, respectively, with PET-CT; and 71.3, 77.2, 60.6, 84.5 and 75.2%, respectively, with contrast-enhanced CT. The SUVmax (7.29±1.83 vs. 5.91±1.65, t=4.15, P=0.000) and MTV (48.20±22.47 vs. 30.21±19.72 cm3, t=4.48, P=0.000) were significantly higher for squamous cell carcinoma (SCC) compared to those for adenocarcinoma (AC). There was a positive correlation between the MTV and SUVmax of the primary tumor (Pearson's r=0.838, P=0.000). Significant differences were observed among differentiation subgroups in the SUVmax and MTV of the primary tumor for both SCC and AC. In conclusion, compared to the postoperative pathological findings, the predictive value of 18F-FDG PET-CT for T and N staging in NSCLC was higher compared to that of contrast-enhanced CT. The FDG uptake of the primary tumor was associated with histological type and differentiation and the difference was statistically significant. Therefore, the SUVmax and MTV of the primary tumor may be valuable indices to partly predict the histological type and grade of differentiation of NSCLC.

Increased serum carcinoembryonic antigen level can predict poor survival of patients with small cell lung cancer.

Increased serum tumor biomarkers are usually associated with huge tumor burden, but the prognostic value of these markers remains controversial. The serum levels of carcinoembryonic antigen (CEA), nerve cell-specific enolase, and lactate dehydrogenase in 281 patients with small cell lung cancer (SCLC) were analyzed in this study. Increased serum CEA levels were observed in 92 (32.7%) patients. Survival was superior in patients with normal serum CEA levels compared with those with increased serum CEA levels. The median survival time, 2-year overall survival (OS) rate, and 3-year OS rate were 19.1 months vs 14.6 months, 42.7% vs 28.3%, and 30.6% vs 14.1%, respectively (P = 0.002). In multivariate analysis, extensive-stage (ES)-SCLC (hazard ratio [HR] = 1.936, P = 0.001), an increased serum CEA level (HR = 1.432, P = 0.021) at diagnosis, and <4 cycles of chemotherapy (ChT) (HR = 0.432, P = 0.001) were independent negative prognostic factors for the OS. Additionally, normal CEA level (HR = 1.678, P = 0.012), treatment modalities including surgery (HR = 1.595, P = 0.049), and ≥ 4 cycles of ChT (HR = 1.880, P = 0.004) were independent positive prognostic factors for OS in patients with local disease. In the subgroup with ES-SCLC, normal serum CEA level (HR = 1.608, P = 0.043), thoracic radiation therapy (HR = 1.744, P = 0.005), and ≥ 4 cycles of ChT (HR = 2.626, P = 0.001) were independent positive prognostic factors for OS.

Feasibility of Elective Nodal Irradiation (ENI) and Involved Field Irradiation (IFI) in Radiotherapy for the Elderly Patients (Aged ≥ 70 Years) with Esophageal Squamous Cell Cancer: A Retrospective Analysis from a Single Institute.

PURPOSE: We conducted a retrospective analysis to assess the feasibility of involved field irradiation (IFI) in elderly patients with esophageal squamous cell cancer (ESCC). MATERIALS AND METHODS: We performed a retrospective review of the records of elderly patients (≥ 70 years) with unresectable ESCC and no distant metastases who received treatment with radiotherapy between January 2009 and March 2013. According to the irradiation volume, patients were allocated into either the elective nodal irradiation (ENI) group or the IFI group. Overall survival (OS), progression-free survival (PFS) and treatment-related toxicities were compared between the two groups. RESULTS: A total of 137 patients were enrolled. Fifty-four patients (39.4%) were allocated to the ENI group and 83 patients (60.6%) to the IFI group, the median doses in the two groups were 60 Gy and 59.4 Gy, respectively. For the entire group, the median survival time (MST) and PFS were 16 months and 12 months, respectively. The median PFS and 3-year PFS rate in the ENI group were 13 months and 20.6%, compared to 11 months and 21.0% in the IFI groups (p = 0.61). The MST and 3-year OS rate in the ENI and IFI groups were 17 months and 26.4% and 15.5 months and 21.7%, respectively (p = 0.25). The rate of grade ≥ 3 acute irradiation esophagitis in the ENI group was significantly higher than that in the IFI group (18.5% vs. 6.0%; p = 0.027). Other grade ≥ 3 treatment-related toxicities did not significantly differ between the two groups. CONCLUSIONS: IFI resulted in decreased irradiation toxicities without sacrificing OS in elderly patients with ESCC.

Risk factors for brain metastases in completely resected small cell lung cancer: a retrospective study to identify patients most likely to benefit from prophylactic cranial irradiation.

BACKGROUND: The role of prophylactic cranial irradiation (PCI) on small cell lung cancer (SCLC) has been established based on the two-stage system of limited versus extensive disease and the treatment modality of chemoradiotherapy. However, the use of PCI after combined-modality treatment with surgery for resectable limited-stage SCLC has not been investigated sufficiently. We conducted a retrospective study to evaluate risk factors for brain metastasis (BM) in patients with surgically resected SCLC to identify those most likely to benefit from PCI. PATIENTS AND METHODS: The records of 126 patients with completely resected SCLC and definitive TNM stage based on histological examination between 2003 and 2009 were reviewed. The cumulative incidence of BM was estimated using the Kaplan-Meier method and differences between the groups were analyzed using the log-rank test. Multivariate Cox regression analysis was applied to assess the risk factors of BM. RESULTS: Twenty-eight patients (22.2%) developed BM at some point during their clinical course. The actuarial risk of developing BM at 3 years was 9.7% in patients with p-stage I disease, 18.5% in patients with p-stage II disease, and 35.4% in patients with p-stage III disease (p = 0.013). The actuarial risk of developing BM at 3 years in patients with LVI was 39.9% compared to 17.5% in patients without LVI (p = 0.003). Multivariate analysis identified pathologic stage (hazard ratio [HR] = 2.013, p = 0.017) and LVI (HR = 1.924, p = 0.039) as independent factors related to increased risk of developing BM. CONCLUSION: Patients with completely resected p-stage II-III SCLC and LVI are at the highest risk for BM.

Clinical value of 18F-FDG PET-CT in detecting primary tumor for patients with carcinoma of unknown primary.

OBJECTIVE: To investigate the clinical value in detecting occult primary tumors with (18)F-FDG PET-CT whole body imaging. METHODS: 120 patients with unknown primary origin were referred for (18)F-FDG PET-CT whole body imaging. All patients were performed (18)F-FDG PET-CT whole body scan. PET-CT images were interpreted by visual inspection and semi-quantitative analysis (standardized uptake value, SUV). Histopathological and formal clinical follow-up findings were used to assess the value of FDG PET-CT. RESULTS: FDG PET-CT was able to detect the primary tumor in 54/120 patients (42.5%). The primary tumors were confirmed by histopathologic and formal clinical follow-up findings, and located in the head and neck (n=17), the lung (n=19), the breast (n=2), the esophagus (n=1), the stomach (n=2), the bile ducts (n=1), the pancreas (n=3), the co1on (n=3), the ovary (n=2), the prostate (n=l), others (n=3). FDG PET results were proved false positive in 9 patients (7.5%), which were located in the head and neck (n=3), the lung (n=1), the gastric (n=1), the colon (n=2), the ovary (n=1), the prostate (n=l). During the clinical follow-up of median 32 months (range, 2-45 months), primary tumor was found in only 5 patients of 60 cases unidentified by PET-CT (breast cancer, gastric cancer, co1on cancer, prostate cancer and urinary tumors, respectively). The sensitivity, specificity, and accuracy of (18)F-FDG PET-CT in the detection of the primary tumor site were 91.5%, 85.2%, and 88.3%, respectively. CONCLUSION: (18)F-FDG PET-CT whole body imaging is both a noninvasive and a very sensitive tomographic whole-body imaging modality, allowing for the detection of a primary tumor and complete tumor staging in single examination, which can contribute substantially to selecting appropriate therapeutic methods and evaluating prognosis. Perhaps (18)F-FDG PET-CT whole body imaging should be used as a first-line imaging modality for patients with carcinoma of unknown primary rather than using it after other diagnostic procedures have failed to identify a primary tumor.

The expression of epidermal growth factor receptor and Ki67 in primary and relapse nasopharyngeal cancer: a micro-evidence for anti-EGFR targeted maintenance therapy.

Epidermal growth factor receptor (EGFR) was expressed widely in NPC. The aim of this study was to investigate the difference of expression of EGFR and Ki67 in primary and recurrence of NPC to supply a micro-evidence of anti-EGFR targeted maintenance therapy for NPC. A retrospective review of 40 patients with clinical stages I-IV b was performed. Chemoradiation was included chemotherapy with fluorouracil plus cisplatin and irradiation for primary and lymph draining regions. All patients were verified tumor locoregional relapse with/or without distant metastasis by CT or MRI after combined CRT by primary and recurrence biopsies. The correlation between EGFR and Ki67 expression inspected by immunohistochemistry was analyzed. The difference of time to recurrence grouped by different expressions of EGFR and Ki67 was compared by log-rank test. The median follow-up time was 20.0 months ± 2.70 (range 23-71). EGFR and Ki67 expression in primary was not significantly different with recurrent focus. A strong significant correlation between EGFR and Ki67 molecules expression was obtained in primary (r = 0.573; P = 0.001) and in recurrent focus (r = 0.698; P = 0.000). A significantly shorter time to locoregional relapse in patients with positive expression of EGFR than patients with negative EGFR expression in primary (P = 0.010) and in relapse (P = 0.022). There was no significant difference of EGFR and Ki67 expression in primary and recurrence tumor expression. The time to relapse was significantly shorter in high expression of EGFR, which might supply micro-evidence to anti-EGFR targeted maintenance therapy for those patients with EGFR overexpression in primary tumor.