Quality assurance in a phase III, multicenter, randomized trial of POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a planning benchmark case.

PURPOSE: To report the planning benchmark case results of the POTENTIAL trial-a multicenter, randomized, phase 3 trial-to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. METHODS: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. RESULTS: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. CONCLUSION: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.

3,3'-Diindolylmethane attenuates inflammation and fibrosis in radiation-induced lung injury by regulating NF-κB/TGF-ß/Smad signaling pathways.

OBJECTIVE: This study aims to investigate the protective effect of 3,3'-diindolylmethane (DIM) on the radiation-induced lung injury (RILI) model and to explore its possible mechanism. Methods: A mouse model of RILI was established by thoracic irradiation, and dexamethasone was used as a positive drug to investigate the effect of DIM on RILI mice. Lung histopathology was analyzed by HE staining and Masson staining. Then the levels of inflammatory cytokines (TGF-ß, TNF-α, IL-1ß, and IL-6), inflammatory cell counts, and activity of MPO were detected. The expression of TGFß1/Smad signaling pathway-related proteins was determined by immunohistochemistry. qPCR was used to analyze the mRNA expression levels of inflammatory factors, α­SMA and COL1A1. The expression of COX-2, NF-κB, IκBα, PI3K, and Akt proteins was assessed by Western blot. Results: Histopathological staining of lung tissues showed that DIM administration alleviated the pulmonary inflammation and fibrosis caused by RILI. Moreover, the content of inflammatory factors such as IL-1ß and IL-6, the expression of NF-κB pathway-related proteins, and the counts of inflammatory cells were inhibited in lung tissue, indicating that DIM can inhibit the NF-κB pathway to reduce inflammation. In addition, DIM could down-regulate the mRNA levels of α-SMA, COL1A1, and downregulate TGFß1, Smad3, and p-Smad2/3 in lung tissues. Conclusion: Our study confirms that DIM has the potential to treat RILI in vivo by inhibiting fibrotic and inflammatory responses in lung tissue through the TGFß/Smad and NF-κB dual pathways, respectively.

Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast-Conserving Surgery in the Modern Treatment Era: A Multicenter, Randomized Controlled Trial From China.

PURPOSE: No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. PATIENTS AND METHODS: Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. RESULTS: Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group (P = .019). CONCLUSION: CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.

Use of off-label nephrology-related drugs in hospitalized pediatric patients: a retrospective study.

BACKGROUND: The information about the use of off-label drugs in pediatric nephrology is still lacking, which leads to increased adverse reactions and medical disputes. We retrospectively analyzed the use of off-label drugs in the in-patient ward of the nephrology department of Nanjing Children's Hospital, China in order to provide more complete information about the use of drugs for children. METHODS: Proportional stratified random sampling was applied to select patients with renal diseases aged 1 month to 18 years, who were admitted to the hospital from October 1, 2012 to September 30, 2013. All nephrology-related drugs prescribed in the hospitalization period and take-home drugs prescribed on discharge were recorded and evaluated as off-label drugs or not from three different perspectives: person-time, prescription, and drug category. RESULTS: From 385 person-times of patients with 1424 prescriptions, according to the ratio between off-label drugs and person-times, drug prescriptions, and drug products, the rates of off-label drugs were 40.78%, 16.64%, and 31.43%, respectively. Low-molecular-weight heparin, alfacalcidol and diltiazem were the most commonly used off-label drugs. Infants and younger children were the high-risk population of off-label drug use. The high rate off-label nephrology-related drug use in children was mainly related to lacking clinical research into drugs in children and the pace of drug label's revision, which cannot follow the development of medical science. CONCLUSION: Approximaely half of pediatric patients with renal diseases are usually prescribed with off-label nephrology-related drugs. Analyzing the off-label conditions from different perspectives may lead to various results. More clinical research into drugs for infants and younger children is needed so as to update drug descriptions.

The 2002 AJCC TNM classification is a better predictor of primary small cell esophageal carcinoma outcome than the VALSG staging system.

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The optimal disease staging system and treatment approaches have not yet been defined. This study aimed to evaluate the prediction of different staging systems for prognosis and treatment options of SCCE. We retrospectively accessed the clinicopathologic characteristics, treatment strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001 and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%, and 13%, respectively. Univariate analysis showed that the 2002 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P = 0.002), Veterans Administration Lung Study Group (VALSG) stage (P = 0.001), predisposing factors (P < 0.001), T category (P = 0.023), and M category (P < 0.001) were prognostic factors for overall survival. Multivariate analysis showed that the 2002 AJCC TNM stage (P < 0.001) was the only independent prognostic factor for survival. The value of the area under the receiver operator characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger than that of VALSG staging system with regard to predicting overall survival (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system improved the prediction of SCCE prognosis; however, the optimal treatment regimen for SCCE remains unclear.

The value of endoscopic ultrasonography in defining longitudinal gross target volumes for esophageal squamous carcinoma.

BACKGROUND AND PURPOSE: To investigate the differences between endoscopic ultrasonography (EUS)-based longitudinal gross target volumes (GTV) (GTV(EUS)) and computed tomography (CT)-based longitudinal GTV (GTV(CT)) in diagnosing esophageal squamous carcinoma. METHODS: Thirty-six patients underwent EUS to define the superior and inferior extents of the tumor by using hemoclips. CT-planning scan was performed with the patient in the supine position during the treatment. GTV(CT) and GTV(EUS) were contoured respectively. The respective lengths (L(CT) and L(EUS)) and spatial locations of longitudinal GTV(CT) and longitudinal GTV(EUS) were compared. RESULTS: The mean LCT was 7.8 ± 3.2 cm and the mean L(EUS) was 7.4 ± 2.7 cm. No statistical difference was found between L(CT) and L(EUS) (P > 0.05) with a correlation coefficient of 0.61 (P<0.05). The mean conformal index was 0.79 ± 0.18 with spatial variations found in 71% (24/34) of the patients. CONCLUSIONS: EUS can provide additional information to CT in defining longitudinal GTV in thoracic esophageal squamous cell carcinoma, especially superficial and submucosal carcinomas, which may contribute to the development of better individual treatment regimens.