The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. We aimed to investigate the correlation ...between the decrease in peripheral blood lymphocytes during radiotherapy (RT) and the spleen irradiation dose in patients with hepatocellular carcinoma (HCC).
The subjects were 59 patients with HCC who had received RT from 2005 to 2014. The Min ALC (minimum value of absolute counts for peripheral blood lymphocytes) was collected from the routine workup for each patient prior to RT and weekly during RT. Spleen dose-volume variables, including the percentage of the organ volume receiving ≥ n Gy (V
) and the mean spleen dose (MSD), were calculated using Eclipse treatment planning. Potential associations between dosimetric variables and the Min ALC were assessed by multiple linear regression analysis.
Peripheral lymphocytes decreased during RT (P < 0.001). The Min ALC correlated with the MSD (P = 0.005), spleen V
(P = 0.001), spleen V
(P = 0.026) and spleen V
(P = 0.018). Controlling for the Karnofsky performance status (KPS), sex, age, Child-Pugh grade, total dose and tumour stage, a multiple linear regression model with bootstrap analysis of 1000 replicates showed that only the spleen V
was correlated with the decrease in the Min ALC (P < 0.05). According to the receiver-operating characteristic (ROC) curve analysis, the predictive cutoff values of the MSD, V
, V
and V
of the spleen for the Min ALC were 227.72 cGy, 17.84, 0.98 and 0.42%, respectively (P = 0.002, P = 0.004, P = 0.007 and P = 0.002, respectively). Furthermore, an MSD ≥ 227.72 cGy (OR = 14.39; 95% CI, 12.18 to 16.60) and V
(OR = 7.99; 95% CI, 6.91 to 9.07) of the spleen significantly predicted the Min ALC.
Higher spleen irradiation doses were significantly correlated with lower Min ALC during RT for HCC. V
should be limited in clinical practice. Maximum sparing for spleen irradiation during RT is recommended to preserve peripheral blood lymphocytes, which may decrease immunosuppression.
Background:
Peripheral blood lymphocytes play an important role in antitumour immunity. We examined the relationship between the minimum absolute lymphocyte counts (Min ALCs) during radiotherapy (RT) ...and clinical outcomes in patients with hepatocellular carcinoma (HCC).
Methods:
Data from a total of 69 HCC patients who had received RT were retrospectively analysed. Peripheral blood lymphocytes were measured before RT, weekly during RT and after RT. Regression and mixed-effect models were used to assess the relationships with and potential predictors of overall survival (OS). Receiver-operating characteristic (ROC) curve analysis was used to define optimal cut-off points of continuous variables for outcomes.
Results:
The median follow up was 30 months (range, 4–68 months). The median survival time (MST), 1-year OS rate and 2-year OS rate of the whole group were 25 months, 51% and 39%, respectively. The average circulating lymphocyte counts declined during RT (1493.19 versus 503.48 cells/µl, p < 0.001). A lower Min ALC was associated with worse OS (p = 0.001), with a cut-off value of 450 cells/µl (sensitivity and specificity, 50% and 70.6%, respectively). The MSTs, 1-year OS rates and 2-year OS rates were 15 months versus 47 months, 27% versus 78% and 4% versus 71% for patients with relatively lower (⩽450 cells/µl) and higher Min ALCs (>450 cells/µl), respectively (p < 0.001). After adjusting for potential confounders, multivariate Cox regression analysis demonstrated that Min ALC independently predicted patients’ OS (HR, 0.32; 95% CI, 0.15–0.69).
Conclusions:
Lower Min ALCs during RT may act as a worse prognostic factor for HCC after RT.
The aim of this study was to determine whether pretreatment status of human epidermal growth factor receptor‐2 (HER‐2) could predict pathologic response to neoadjuvant chemoradiotherapy (nCRT) and ...outcomes for patients with locally advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC received standardized multimodal treatment. Their HER‐2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. Twenty‐two cases in 119 patients assessed as IHC3+ or IHC2+ plus gene‐amplified were determined as HER‐2 positive. Positive HER‐2 status was not associated with any pretreatment clinicopathologic parameters (P > 0.05). HER‐2 status could not predict pathologic response to nCRT based on downstaging (P = 0.210) and tumor regression grade (P = 0.085) but it provides us with a trend that HER‐2‐positive tumors may be resistant to nCRT. Positive HER‐2 status was significantly associated with poor 5‐year disease‐free survival (P = 0.015) and 5‐year overall survival (P = 0.026). It can act as a worse prognostic factor for LARC patients.
HER‐2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER‐2 positivity before nCRT were significantly associated with poor 5‐year disease‐free survival (P = 0.015) and 5‐year overall survival (P = 0.026). HER‐2 status can not predict tumor response to nCRT in LARC, but it provides us with a trend that HER‐2 positive tumor may be resistant to nCRT.
Preoperative chemoradiotherapy (CRT) combined with surgery has become a standard treatment strategy for patients with locally advanced rectal cancer (LARC). The pathological response is an important ...prognostic factor for LARC. The variety of tumor responses has increased the need to find a useful predictive model for the response to CRT to identify patients who will really benefit from this multimodal treatment. Magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), serum carcinoembryogenic antigen (CEA), molecular biomarkers analyzed by immunohistochemistry and gene expression profiling are the most used predictive models in LARC. The majority of predictors have yielded encouraging results, but there is still controversy. Diffusion-weighted MRI may be the best model to detect the dynamic changes of rectal cancer and predict the response at an early stage. Gene expression profiling and single nucleotide polymorphisms hold considerable promise to unveil the underlying complex genetics of response to CRT. Because each parameter has its own inherent shortcomings, combined models may be the future trend to predict the response.
Patients with esophageal small cell carcinoma undergoing definitive chemoradiotherapy (CRT) seem to have disparity in tumor response. The identification of CRT sensitivity-related tumor markers would ...be helpful for selecting patients most likely to benefit from CRT. The aim of this study was to examine the predictive value of biological markers in small cell carcinoma of the esophagus (SCEC) patients treated with definitive CRT. Pretreatment serum levels of neurone-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and carcinoembryonic antigen (CEA) were measured by immunoradiometric assays, while the tumor responses were evaluated according to the World Health Organization response criteria. The relationships between pretreatment expression of NSE, CYFRA21-1, CEA, and the tumor response to CRT were analyzed. The effective rates (complete response + partial response) in NSE high and low groups were 10.80 % (9/82) and 37.98 % (31/82), respectively (
P
= 0.003).The results from statistical analysis indicated that the effectiveness of CRT was significantly associated with the serum levels of NSE before treatment (
P
= 0.002). The overall survival (OS) of the patients with high NSE levels was worse than that of those with low NSE levels (
P
= 0.004). In multivariate analysis, low level of NSE was the most significant independent predictor of good OS (
P
= 0.003). The result showed a promising predictive value of NSE regarding to the sensitivity of tumors to CRT. NSE may be a reliable surrogate marker of CRT efficacy in patients with SCEC.
Patients with advanced non-small cell lung cancer (NSCLC) seem to have disparity in prognosis. Accurate prediction of prognosis could be useful in the future to predict individual risk and to develop ...more aggressive or alternative treatment strategies.
To evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with NSCLC.
We retrospectively reviewed 120 patients with pathologically proven NSCLC (61 squamous cell carcinomas and 59 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. Pretreatment variables (age, sex, American Joint Committee on Cancer AJCC stage, histological type, SUVmax, and MTV) were analyzed to identify their correlation with two-year survival. To further evaluate and compare the predictive value of PET parameters, MTV, and SUVmax, time-dependent receiver-operating characteristic curve (ROC) analysis was used.
In the univariate analysis, AJCC stage, histological type, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis, independent prognostic factors associated with decreased two-year survival were AJCC stage (hazard ratio HR 2.236, P = 0.003), histological type (HR 2.038, P = 0. 004), and MTV (HR 1.016, P = 0.001). SUVmax was not a significant factor (HR 0.96, P = 0.490). On time-dependent ROC analysis, MTV showed good predictive performance for two-year survival consistently better than SUVmax.
MTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with advanced NSCLC.
Objectives
The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma.
Methods
Ninety-eight patients with nonmetastatic ...rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed.
Results
The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191).
Conclusions
Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.
Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer‑associated signaling pathways. Radiation resistance is a major problem ...encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)‑21 in the development of radiation resistance in non‑small cell lung cancer cells. A radiation‑resistant cell line was generated from A549 cells. Significant upregulation of miR‑21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR‑21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia‑inducible factor‑1α (HIF1α) was upregulated by miR‑21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR‑21‑inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR‑21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.
Inflammatory myofibroblastic tumor (IMT) is a rare disease. We report a rare case of inflammatory myofibroblastic tumor occurs in the mediastinum. Chest contrast-enhanced computed tomography (CT) ...showed a heterogeneously enhanced irregular mass in the anterior mediastinum; a small pericardial effusion was also noted. The diagnosis was confirmed by histopathology and immunohistochemical study.
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