Hongsheng Li

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

PURPOSEnTo 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).nnnMETHODS AND MATERIALSnEligible 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).nnnRESULTSnThirty-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).nnnCONCLUSIONnThe 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.

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

BACKGROUNDnMicroRNA 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.nnnMETHODSnStudies 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.nnnRESULTSnTwenty-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.

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

OBJECTIVEnTo 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).nnnMETHODSnIn 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnRadiotherapy 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.

Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer.

ObjectivesConcurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy. MethodsThe chemotherapy was cisplatin (25 mg/m2×3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m2. The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [18F] fluorodeoxyglucose positron emission tomography computed tomography imaging. To spare functional lung, single photon emission photography lung perfusion imaging was used to optimize the plans. The total radiation dose was limited such that the V20 of bilateral lung is no more than 35%. ResultsNine patients with LANSCLC were enrolled in this study. The median radiation dose was 70.8 Gy. The response rate was 66.7% with a complete remission rate of 33.3%. Toxicity was mild with only 1 patient experiencing dose limiting toxicity in 500 mg/m2 level. Obviously, the maximum tolerated dose was not reached as per the definition. As the systemically active chemotherapy dose was reached, further dose escalation was discontinued, and the recommended dose of pemetrexed for a phase II study was 500 mg/m2. ConclusionsThe combination of pemetrexed and cisplatin with concurrent LCAF IMRT optimized based on single photon emission photography lung perfusion imaging is well tolerated in patients with LANSCLC. Full therapeutic doses of the chemotherapy can be safely administered. The initial results showed signs of efficacy.

Significant associations between GSTM1 / GSTT1 polymorphisms and nasopharyngeal cancer risk

Glutathione S-transferases play a critical role in the detoxification and elimination of electrophilic carcinogens by conjugating them to glutathione. Homozygous deletions of GSTM1 and GSTT1 have been suggested as risk factors for some cancers, including colorectal, pancreatic, and esophageal cancers. Results of previous individual studies published to estimate the associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer (NPC) risk remained controversial. Thus, we carried out a meta-analysis by pooling the odds ratios (ORs) with corresponding 95xa0% confidence intervals (95xa0% CIs) of all currently available case–control studies to shed some light on the contradictory finding. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 20, 2012 was performed to identify eligible studies. A total of 15 separate publications involving 2,226 NPC cases and 3,339 controls were finally included into this meta-analysis. The meta-analysis of total studies showed that the null genotypes of GSTM1 and GSTT1 were both significantly associated with increased risk of NPC (for GSTM1: ORu2009=u20091.54, 95xa0% CI 1.28–1.86, PORu2009<u20090.001; for GSTT1: ORu2009=u20092.25, 95xa0% CI 1.50–3.36, PORu2009<u20090.001). Subgroup analysis by ethnicity suggested that carriers of both GSTM1 and GSTT1 null genotypes in Asians were more susceptible to NPC. Additionally, in the subgroup analysis based on the sample size, significant associations of the GSTM1 and GSTT1 polymorphisms with NPC susceptibility were identified among studies both with larger case sample size (number of cases ≥100) and smaller case sample size (number of cases <100). Sensitivity analysis confirmed the stability of our results. These results indicate that the GSTM1 and GSTT1 polymorphisms may play crucial roles in the development of NPC, especially in Asians.

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.

Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy

BackgroundTo analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy.MethodsSeventy-six NSCLC patients treated with concomitant chemoradiotherapy were retrospectively analyzed. Forty-one patients received concomitant chemoradiotherapy with vinorelbine/cisplatin (VC), 35 with docetaxel/cisplatin (DC). AE was graded according to criteria of the Radiation Therapy Oncology Group (RTOG). The following clinical and dosimetric parameters were analyzed: gender, age, clinical stage, Karnofsky performance status (KPS), pretreatment weight loss, concomitant chemotherapy agents (CCA) (VC vs. DC), percentage of esophagus volume treated to ≥20 (V20), ≥30 (V30), ≥40 (V40), ≥50 (V50) and ≥60 Gy (V60), and the maximum (Dmax) and mean doses (Dmean) delivered to esophagus. Univariate and multivariate logistic regression analysis were used to test the association between the different factors and AE.ResultsSeventy patients developed AE (Grade 1, 19 patients; Grade 2, 36 patients; and Grade 3, 15 patients). By multivariate logistic regression analysis, V40 was the only statistically significant factor associated with Grade ≥2 AE (p<0.001, ORu2009=u20091.159). A V40 of <23% had a 33.3% (10/30) risk of Grade ≥2 AE, which increased to 89.1% (41/46) with a V40 of ≥23% (p<0.001). CCA (p =0.01; ORu2009=u20099.686) and V50 (p<0.001; ORu2009=u20091.122) were most significantly correlated with grade 3 AE. A V50 of <26.5% had a 6.7% (3/45) risk of Grade 3 AE, which increased to 38.7% (12/31) with a V50 of ≥26.5% (pu2009=u20090.001). On the linear regression analysis, V50 and CCA were significant independent factors affecting AE duration. Patients who received concomitant chemotherapy with VC had a decreased risk of grade 3 AE and shorter duration compared with DC.ConclusionsConcomitant chemotherapy agents have potential influence on AE. Concomitant chemotherapy with VC led to lower risk of AE compared with that using DC. V40 and V50 of esophagus can predict grade ≥2 and ≥3 AE, respectively.

Long-Term Outcome of Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Patients: Comparison Between Treatment with Radiotherapy Alone and Chemoradiotherapy

The purpose of this study is to assess the long-term effect of sensorineural hearing loss (SNHL) resulted from radiotherapy (RT) alone versus chemoradiotherapy in nasopharyngeal carcinoma patients (NPC). Seventy-two patients initially diagnosed with NPC were enrolled from Shandong Tumor Hospital between March 2003 and May 2007. They were assigned into two groups: RT alone and chemoradiotherapy according to the different treatment regimens. Intensity-modulated radiation therapy was applied for both groups, concurrent and adjuvant cisplatin were administered for chemoradiotherapy group additionally. Hearing threshold test was performed at various time periods after completion of RT. Mean radiation dose to the cochlea in each ear was calculated to determine the correlation between cochlear dose and SNHL. We found that the hearing loss is more severe in the chemoradiotherapy group compared with RT group, from completion of RT up to the 5xa0years of follow-up period. This is especially obvious in the high frequency range. Hearing level is seriously damaged when cochlea dose exceeds 46xa0GY. We concluded that concurrent/adjuvant chemotherapy plus RT aggravates SNHL in NPC patients than RT alone and thus inner ear tissue tolerance should be redefined in those patients.

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.

Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma

The purpose of this study was to investigate clinical–biological factors which could predict the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma (ESCC). One hundred eighty-one patients with stages I–IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), albumin (A) as well as hemoglobin (HB) concentration were measured before the initiation of chemoradiotherapy (CRT). The cutoff values of CYFRA21-1, CEA, and A were defined as 3.4xa0ng/ml, 3.3xa0ng/ml, 3.5xa0g/dl, respectively. HB was divided into three levels: <12.0, 12.0–14.0, and >14.0xa0g/dl. Clinical factors such as sex, age, tumor location, primary cancer length, and tumor–node–metastasis stage were also evaluated. The effective rate (complete responseu2009+u2009partial response) of the primary tumor estimated by computed tomography was 60.71% (17 out of 28) in patients with CEA high group while 92.54% (62 out of 67) in patients with CEA low group (Pu2009=u20090.000) and 62.50% (20 out of 32) in patients with CYFRA21-1 high group while 92.98% (53 out of 57) in patients with CYFRA21-1 low group (Pu2009=u20090.000). HB levels before and during CRT were also associated with the effectiveness (Pu2009=u20090.005, 0.033, respectively). HB levels before CRT at 12.0–14.0xa0g/dl were associated with the best effectiveness, followed by >14.0 and <12.0xa0g/dl (effective rates 88.89% vs. 83.75%, 62.07%, respectively, Pu2009=u20090.005). HB levels during CRT also showed similar results (effective rates 87.80% vs. 85.41%, 70.59%, respectively, Pu2009=u20090.033). Furthermore, according to numbers of the above risk factors, the sensitivity of CRT was higher in patients with zero to one risk factors than those with two to four risk factors (Pu2009=u20090.023). CYFRA21-1 and CEA as well as HB and their combination may be helpful in predicting the sensitivity to CRT of ESCC. However, the results should be further confirmed in larger, more homogeneous studies.