Rui Feng

Prognostic value of serial [18F]fluorodeoxyglucose PET-CT uptake in stage III patients with non-small cell lung cancer treated by concurrent chemoradiotherapy.

OBJECTIVEnTo evaluate (18)FDG PET-CT for the assessment of therapy response and prediction of patient outcome after concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC).nnnMETHODSnForty-six patients with pathologically proven stage III NSCLC had 2 serial FDG PET-CT scans, before and during CCRT. The maximum standardized uptake value (SUV(max)) of the primary lung lesion was calculated. The value changes of SUV(max) before and during treatment were calculated according to the following equation: SUV=(SUV(before)-SUV(during))100%/SUV(before). The relationship between changes of the SUV(max) and the therapy response as well as long-term survival was studied in the responsive and non-responsive groups after CCRT.nnnRESULTSnOf the 46 enrolled patients, after a medicine follow-up of 2 years, the initial SUV(max) in the responsive and non-responsive groups was 7.59±3.14 and 14.72±4.67, respectively. The SUV(max) during treatment in the two groups was 2.89±1.39 and 9.82±3.31, respectively. Significant difference (P=0.001; P=0.001) in SUV(max) was observed either before or during treatment. Furthermore, the percent change of SUV(max) before and during treatment was 61.91±86.69 and 33.56±90.37, respectively. There was significant difference between these two groups (P=0.007). In addition, the 1-year survival rate in the responsive and non-responsive group was 73% and 69%, respectively. The 2-year survival rate in the two groups was 40% and 37%, respectively. There was significant difference between these two groups (P=0.001).nnnCONCLUSIONSn(18)FDG PET-CT is an effective method in the prediction of therapy response in patients with stage III NSCLC. The analysis of percent change of SUV(max) provides additional value in early prediction of therapy response and patient outcome.

Measurement of tumor volume by PET to evaluate prognosis in patients with advanced non-small cell lung cancer treated by non-surgical therapy

Background 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. Purpose To evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with NSCLC. Material and Methods 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. Results 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. Conclusion 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.

A comparison of liver protection among 3-D conformal radiotherapy, intensity-modulated radiotherapy and RapidArc for hepatocellular carcinoma.

PurposeThe analysis was designed to compare dosimetric parameters among 3-D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and RapidArc (RA) to identify which can achieve the lowest risk of radiation-induced liver disease (RILD) for hepatocellular carcinoma (HCC).MethodsTwenty patients with HCC were enrolled in this study. Dosimetric values for 3DCRT, IMRT, and RA were calculated for total dose of 50 Gy/25f. The percentage of the normal liver volume receiving >40, >30, >20, >10, and >5 Gy (V40, V30, V20, V10 and V5) were evaluated to determine liver toxicity. V5, V10, V20, V30 and Dmean of liver were compared as predicting parameters for RILD. Other parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V110%) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (Dmean) for the organs at risk (OARs) and the maximal dose at 1% volume (D1%) for the spinal cord.ResultsThe Dmean of IMRT was higher than 3DCRT (pu2009=u20090.045). For V5, there was a significant difference: RAu2009>u2009IMRT >3DCRT (p <0.05). 3DCRT had a lower V10 and higher V20, V30 values for liver than RA (p <0.05). RA and IMRT achieved significantly better CI and lower V110% values than 3DCRT (p <0.05). RA had better HI, lower MUs and shorter delivery time than 3DCRT or IMRT (p <0.05).ConclusionFor right lobe tumors, RapidArc may have the lowest risk of RILD with the lowest V20 and V30 compared with 3DCRT or IMRT. For diameters of tumors >8xa0cm in our study, the value of Dmean for 3DCRT was lower than IMRT or RapidArc. This may indicate that 3DCRT is more suitable for larger tumors.

Predictors of sensitivity to preoperative chemoradiotherapy of rectal adenocarcinoma.

OBJECTIVESnThe purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma.nnnMETHODSnNinety-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.nnnRESULTSnThe 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).nnnCONCLUSIONSnPretreatment 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.

The prognostic role of EZH2 expression in rectal cancer patients treated with neoadjuvant chemoradiotherapy

BackgroundNeoadjuvant chemoradiotherapy (nCRT) combined with surgery has been implemented as a standard treatment strategy in locally advanced rectal cancer (LARC). However, there is a wide spectrum of response to nCRT. The aim of this study was to determine whether enhancer of zeste homologue 2 (EZH2 ) expression could predict response to nCRT and outcomes for patients in LARC.MethodThe study examined the EZH2 expression in 112 biopsies by immohistochemistry. The associations between EZH2 and clinical characters were analyzed.ResultsEZH2 expression in biopsy tissue was significantly related to increased tumor cell proliferation, as assessed by Ki-67 expression with a cutoff value of 37% (p <0.001). High EZH2 expression was correlated closely with low differentiation (pu2009=u20090.029), high CEA level (pu2009=u20090.041), T4 status (pu2009=u20090.011) and node metastasis (p =0.045). By univariate and multivariate analysis, we observed low EZH2 expression could reliably and independently predict the good response to nCRT ( pu2009=u20090.026 and pu2009=u20090.023) and down-staging ( pu2009=u20090.021 and pu2009=u20090.027). In univariate analysis, high EZH2 expression was significantly associated with poor 5-year disease-free survival (pu2009=u20090.025) and 5-year overall survival (pu2009=u20090.032). In multivariate analysis, EZH2 was a prognostic factor for 5-year DFS (HRu2009=u20092.287; 95% CI 1.137-4.602, pu2009=u20090.020) but not for 5-year OS (HRu2009=u20092.182; 95% CI 0.940-5.364, pu2009=u20090.069).ConclusionOur study revealed that low EZH2 expression in biopsy tissue might be a useful predictive factor of good tumor response to nCRT and longer 5-year DFS in patients with LARC. However this is a relatively small retrospective study, to further validate the role of EZH2 in rectal cancer, large consistent cohort studies are needed.

Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: Association with response to neoadjuvant therapy and prognosis

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.

NSE can predict the sensitivity to definitive chemoradiotherapy of small cell carcinoma of esophagus

AbstractPatients 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 responsexa0+xa0partial response) in NSE high and low groups were 10.80xa0% (9/82) and 37.98xa0% (31/82), respectively (Pxa0=xa00.003).The results from statistical analysis indicated that the effectiveness of CRT was significantly associated with the serum levels of NSE before treatment (Pxa0=xa00.002). The overall survival (OS) of the patients with high NSE levels was worse than that of those with low NSE levels (Pxa0=xa00.004). In multivariate analysis, low level of NSE was the most significant independent predictor of good OS (Pxa0=xa00.003). 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.n

Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis

Purpose Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. Results Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. Conclusion Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment.

Prognostic value of serum γ‑glutamyl transferase in unresectable hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization combined with conformal radiotherapy

The detection of γ-glutamyl transferase (GGT) has previously been reported to be useful in the diagnosis in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the baseline serum GGT levels in patients with intermediate HCC (Barcelona Clinic Liver Cancer stage B) following treatment with transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT). A total of 154 intermediate HCC patients with Child-Pugh grade A were retrospectively investigated. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold for the GGT serum levels, and univariate and multivariate analyses were used to establish the prognostic factors. The median overall survival (OS) time was 24.3 months. The optimal threshold for GGT was 85 U/L (sensitivity, 75.13%; specificity, 69.81%; and area under the ROC curve, 0.763). The one-, three- and five-year OS rates were 79.9, 49.7 and 17.2%, respectively, for patients with low GGT levels (≤85 U/l) and 52.3, 22.1 and 8.5%, respectively, for patients with high GGT levels (>85 U/l) (P=0.007). The results indicated that the serum GGT level was an independent prognostic factor (hazard ratio=2.32; P=0.007) for OS. Furthermore, in subgroups stratified according to serum α-fetoprotein, gross tumor volume and radiation dose, serum GGT was also found to correlate with OS (P<0.05). Therefore, the baseline GGT level may be a significant prognostic factor for intermediate HCC patients with Child-Pugh grade A following TACE combined with 3DCRT.

Superiority of helical tomotherapy on liver sparing and dose escalation in hepatocellular carcinoma: a comparison study of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy.

Background and purpose To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. Patients and methods Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. Results The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower Dmean (mean dose) and V20 (Vn, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). Dmean of nontarget normal liver and V30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. Conclusion HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy.