Baosheng Li

Which is the optimal biologically effective dose of stereotactic body radiotherapy for Stage I non-small-cell lung cancer? A meta-analysis.

PURPOSE To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data were combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). RESULTS Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p ≤ 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). CONCLUSION The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.

Value of Metabolic Tumor Volume on Repeated 18F-FDG PET/CT for Early Prediction of Survival in Locally Advanced Non–Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

The aim of this study was to investigate the value of standardized uptake values (SUVs) and metabolic tumor volume (MTV) in 18F-FDG PET/CT to predict the survival of patients with locally advanced non–small cell lung cancer during the early stage of concurrent chemoradiotherapy. Methods: A total of 53 patients were included in the prospective study. All patients were evaluated by 18F-FDG PET before and after 40 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy regimen. Semiquantitative assessment was used to determine the maximum and mean SUVs (SUVmax and SUVmean, respectively) and MTV of the primary tumor. The cutoffs for changes in SUVmax, SUVmean, and MTV (37.2%, 41.7%, and 29.7%, respectively) determined in a previous study were used with Kaplan–Meier curves to separate the groups. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analysis. Results: Overall survival (OS) at 1 and 2 y was 83.0% (46/53) and 52.8% (28/53), respectively. Survival curves for SUVmean and MTV were significantly different using the cutoffs. However, Cox regression analysis showed that the only prognostic factor for OS was a decrease in MTV. Conclusion: The use of repeated 18F-FDG PET to assess survival early during concurrent chemoradiotherapy is possible in patients with locally advanced non–small cell lung cancer. A decrease in MTV according to 18F-FDG uptake by the primary tumor correlates with higher long-term OS.

The expression of miR-21 and miR-375 predict prognosis of esophageal cancer

BACKGROUND MicroRNA is a class of small, well-conserved, non-coding RNAs, and could play a potential role as diagnostic and prognostic biomarkers of esophageal cancers. We aimed to review comprehensively the evidence of microRNA as prognostic biomarkers in esophageal cancers. METHODS Studies were identified by searching PubMed, Embase and Web of Science until November 2013. Descriptive characteristics of studies were described and an additional meta-analysis for specific microRNAs which were studied most frequently was performed. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. Fixed model or random model method was chosen depending on the heterogeneity among the studies. RESULTS Twenty-two studies including a total of 1946 participants were enrolled after a strict filtering and qualifying process. Among 33 prognostic microRNAs identified for esophageal cancer, miR-21 and miR-375 appeared more frequently. The median study size was 70.5 patients (29-249 patients) and the median HR was 3.305 (IQR=1.615-7.31). For the studies evaluating miR-21s association with overall survival (OS), the pooled HR suggested that high level of miR-21 has a negative impact on OS (HR=1.52[1.17-1.98], P=0.001). As for miR-375, the pooled HR for OS (high/low) was 0.53 (95% CI: 0.39-0.73, P<0.001), indicated that low level of miR-375 has a negative impact on OS. These results indicated that microRNAs show promising associations with prognosis in esophageal cancer. Up-regulation of miR-21 and down-regulation of miR-375 can predict unfavourable prognosis in esophageal cancer.

CYFRA21-1 and CEA are useful markers for predicting the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma.

Background: Chemoradiotherapy (CRT) is currently performed for patients with advanced esophageal carcinoma. Sensitivity of tumours to CRT differs from one case to another and may be influenced by the expression of biological molecules. The aim of this study was to identify biological markers which could predict sensitivities of esophageal squamous cell carcinoma (ESCC) to CRT. Methods: A total of 84 patients with stage I–IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) levels were measured before CRT by enzyme-linked immunosorbent assays in patients with primary ESCCs using 3.4 ng ml−1 and 3.3 ng ml−1, respectively, as cut-off values. The relationships between pretreatment expression of CYFRA 21-1 and CEA and the effectiveness of CRT were analysed. Results: The complete response (CR) rates of the primary tumours estimated by computed tomography in patients with high levels of CYFRA21-1 and CEA were 10% (3/30) and 4.2% (1/24), while in cases with low CYFRA21-1 and CEA the CR rates were 50% (27/54) and 48.3% (29/60), respectively (p = 0.002 and 0.003). The effective rates (CR+PR) in CYFRA21-1 high and low groups were 60% (18/30) and 96.3% (52/54), while in CEA high and low groups they were 58.3% (14/24) and 93.3% (56/60), respectively (p = 0.013 and 0.013). Conclusion: CYFRA21-1 and CEA may be helpful in predicting the responsiveness in ESCC of primary lesions to CRT, although the results should be confirmed in larger, more homogeneous studies.

Feasibility of Shrinking Field Radiation Therapy through 18F-FDG PET/CT after 40 Gy for Stage III Non-Small Cell Lung Cancers

OBJECTIVE To explore the feasibility of shrinking field technique after 40 Gy radiation through 18F-FDG PET/ CT during treatment for patients with stage III non-small cell lung cancer (NSCLC). METHODS In 66 consecutive patients with local-advanced NSCLC, 18F-FDG PET/CT scanning was performed prior to treatment and repeated after 40 Gy. Conventionally fractionated IMRT or CRT plans to a median total dose of 66 Gy (range, 60-78 Gy) were generated. The target volumes were delineated in composite images of CT and PET. Plan 1 was designed for 40 Gy to the initial planning target volume (PTV) with a subsequent 20-28 Gy-boost to the shrunken PTV. Plan 2 was delivering the same dose to the initial PTV without shrinking field. Accumulated doses of normal tissues were calculated using deformable image registration during the treatment course. RESULTS The median GTV and PTV reduction were 35% and 30% after 40 Gy treatment. Target volume reduction was correlated with chemotherapy and sex. In plan 2, delivering the same dose to the initial PTV could have only been achieved in 10 (15.2%) patients. Significant differences (p<0.05) were observed regarding doses to the lung, spinal cord, esophagus and heart. CONCLUSIONS Radiotherapy adaptive to tumor shrinkage determined by repeated 18F-FDG PET/CT after 40 Gy during treatment course might be feasible to spare more normal tissues, and has the potential to allow dose escalation and increased local control.

Risk factors for hepatitis B virus reactivation after conformal radiotherapy in patients with hepatocellular carcinoma

This study investigated whether conformal radiotherapy affects hepatitis B virus (HBV) reactivation, and the risk factors for HBV reactivation in patients with HBV‐related hepatocellular carcinoma (HCC). Sixty‐nine patients with HCC were included in this retrospective study. Before radiotherapy (RT), all patients underwent imaging examinations and some baseline examinations, including CBC, liver function test, renal function test, α‐fetoprotein level, hepatitis B (HB) surface antigen, HB surface Ab, HB e antigen, HB e Ab, and serum HBV DNA quantification. During the period of RT and at least 16 weeks after the end of RT, CBCs were carried out weekly and the other tests were monitored monthly or more frequently if necessary. The clinical features and dosimetric parameters of RT were recorded. Univariate and multivariate logistic regression algorithms were used to analyze the risk factors of HBV reactivation. The incidence of complications in the study population was as follows: radiation‐induced liver disease, 17.4%; HBV reactivation, 24.6%; and HBV reactivation‐induced hepatitis, 21.7%. The HBV DNA level and dose volume parameters including normal liver volume, V20, and mean dose were associated with HBV reactivation. There was a relatively high incidence of HBV reactivation in HCC patients after the end of conformal RT. The serum HBV DNA level and some dosimetric parameters related to normal liver, including normal liver volume, V20, and mean dose, were the prognosis factors of HBV reactivation and should be carefully considered before conformal RT.

A Clinical Study of Shrinking Field Radiation Therapy Based on 18F-FDG PET/CT for Stage III Non-Small Cell Lung Cancer

The aim is to investigate the feasibility of shrinking field technique after 40 Gy for stage III non-small cell lung cancer (NSCLC) during radiation therapy. Eighty-seven consecutive patients treated with intensity-modulated radiation therapy or three-dimensional conformal radiation therapy were enrolled in this study. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning was performed prior to treatment and repeated after 40 Gy, and the delineation of target volume was based on fused images of PET and CT. After 40 Gy of conventional fractionated radiotherapy to the initial planning target volume (PTV), a boost of 19.6–39.2 Gy was delivered to the shrunken PTV through late course accelerated hyperfractionated radiotherapy, and the median total dose was 66.0 Gy (range, 59.6–79.2 Gy). Gross tumor volume (GTV) and PTV regressions were recorded, and prescription doses with or without shrinking field were calculated. Local recurrence patterns were investigated through follow-up. The tumor volumes regressed in 84 (96.6%) patients and increased in 3 (3.4%) patients after 40 Gy. The mean GTV and PTV reduction was 38% (range, −13–95%) and 30% (range, −5–95%). Mean total prescription dose escalated from 62.0 Gy to 68.5 Gy through shrinking field technique. The median follow-up was 17 months, ranging from 5 to 46 months, and the 1- and 2-year overall survival rates in our study were 74.7% and 34.6%. The response rate was 79.5%, and radiation toxicity was acceptable. Tumor progression occurred in 67.8% (59/87) patients. Numbers of patients who had outfield, infield and both infield and outfield recurrences were 3 (3.4%), 26 (29.5%), and 3 (3.4%), respectively. In conclusion, significant tumor regression was observed after 40 Gy, and radiation dose escalated after shrinking field with acceptable toxicity and outfield relapse. Shrinking field radiotherapy based on 18F-FDG PET/CT after 40 Gy was safe and feasible for stage III NSCLC.

CYFRA21-1 can predict the sensitivity to chemoradiotherapy of non-small-cell lung carcinoma

Background: The increasing panel of systemic therapies enables the individual management of lung cancer patients, even in advanced stages. However, predictive tools indicating the efficacy of chemoradiotherapy (CRT) are badly needed. Aims: To determine the tumour markers for predicting the therapeutic effect in non-small-cell lung carcinoma (NSCLC) patients treated with CRT. Methods: The serum levels of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neurone-specific enolase (NSE) and carcinoembryonic antigen (CEA) were measured before CRT by enzyme-linked immunosorbent assays, while the tumour responses were assessed according to the World Health Organization (WHO) response criteria. The relationships between pretreatment expression of CYFRA21-1, NSE, CEA and the effectiveness of CRT were analysed. Results: The complete response (CR) rate of the primary tumours estimated by computed tomography in patients with high levels of CYFRA21-1 was 2.9% (2/68) while in cases with low CYFRA21-1 it was 20.3% (12/59) (p = 0.005). The effective rates (CR+PR) in CYFRA21-1 high and low groups were 52.9% (36/68) and 72.9% (43/59), respectively (p = 0.022). Conclusions: CYFRA21-1 may be a reliable surrogate marker of CRT efficacy in patients with NSCLC.

Explore the Radiotherapeutic Clinical Target Volume Delineation for Thoracic Esophageal Squamous Cell Carcinoma from the Pattern of Lymphatic Metastases

Introduction: Esophageal carcinoma is characterized by a high frequency of lymph node metastasis (LNM). It is difficult to accurately define the radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma (ESCC), because the LNM rate and the included node level varied greatly among previous studies. This study aimed to determine which node level should be included for radiotherapy by analyzing LNM rate in thoracic ESCC patients. Methods: The clinicopathological factors related to LNM were analyzed using the &khgr;2 test. The sites with LNM rate higher than 15%, an empirical cutoff value, were considered as high-risk areas and were included in clinical target volume of thoracic ESCC patients for radiotherapy. Results: This study included 1893 thoracic ESCC patients treated at Shandong Cancer Hospital, Jinan, China. The rates of LNM in patients with upper thoracic tumors were 14.6% cervical, 29.3% upper mediastinal, 8.5% middle mediastinal, 9.8% lower mediastinal, and 7.3% abdominal, respectively. The rates of LNM in patients with middle thoracic tumors were 4.3%, 5.0%, 32.9%, 2.5%, and 14.9%, respectively. The rates of LNM in patients with lower thoracic tumors were 2%, 2.2% 15.4%, 38.1%, and 27.5%, respectively. Independent prognostic factors for LNM included length of tumor, histologic differentiation, and depth of tumor invasion (p < 0.001). Conclusions: Irradiation of the selective regional lymph node and the correlated lymphatic drainage regions should be performed according to the clinicopathological factors. For the large, deeply invasive longer tumors and poorly differentiated thoracic ESCC, the irradiation field should be enlarged appropriately.

Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume delineation of regional lymph node in patients with gastric carcinoma

PURPOSE To study the pattern of lymph node metastases (LNM) of gastric carcinoma (GC) and clarify the clinical target volume delineation of regional lymph node (CTVn). METHODS AND MATERIALS The pattern of LNM of a total of 875 GC patients who had undergone gastrectomy and lymphadenectomy with more than 15 lymph nodes retrieved were retrospectively examined. The clinicopathologic factors related to LNM were analyzed using logistic regression analysis and linear regression. RESULTS The rate of LNM in patients with upper GC was 75.3%, in middle ones 78.9%, in lower ones 64.9%, and 82.2% in patients with whole GCs. In terms of the ratio between metastatic and examined lymph nodes (N ratio) of GC patients, it was 35.8% in patients with upper tumors, 36.6% in middle ones, 27.6% in lower ones, and 51.0% in whole GCs. The maximum diameter and T stage of tumor emerged as statistically significant risk factors of the rate of LNM of GC (P<0.001, 0.001, respectively; HR=1.172, 2.132, respectively; 95% confidence interval: 1.083-1.268, 1.777-2.558, respectively). T stage (P<0.001), the maximum diameter of tumor (P<0.001), tumor differentiation (P=0.018) and macroscopic types of tumor (P=0.030) were significantly associated with N ratio. Our material showed an orderly spread to stations 1-16 clearly related to the position of the tumor (P<0. 001), nevertheless, there was no statistical difference between different locations of tumor with regards of the rate of LNM (P=0.614, HR=0.945, 95% confidence interval: 0.759-1.177) as well as N ratio (P>0.05). CONCLUSIONS The pattern of LNM in GC is mainly correlated with the maximum diameter of tumor, T stage, macroscopic types and histologic differentiation. Rate of LNM and N ratio can be recommended as applicable parameters for lymph nodes involvement of GC. These factors should be considered comprehensively to design the CTVn for radiotherapy (RT) of GC. Selective regional irradiation including the correlated lymphatic drainage regions should be performed as well.