Photoactivated Circularly Polarized Luminescent Organic Radicals in Doped Amorphous Polymer.

Luminescent organic radicals, especially those with photoactivated circularly polarized luminescence (CPL) features, hold great significance for cutting-edge optoelectronic applications, but their development still remains a challenge. In this study, we propose a novel strategy to achieve photoactivated CPL radicals by bonding two phosphine centers within an axial chiral system, yielding a compound of R/S-5,5-bis(diphenylphosphino)-4,4'-bibenzo[d][1,3]dioxole (R/S-BDP). The photoactivated R/S-BDP molecules in polymer matrix display a robust quantum yield of 19.8 % and a dissymmetry factor (glum) of 1.2×10-4, marking this work as the first example of photoactivated CPL radicals. Furthermore, the glum is improved to 1.0×10-2 by using a liquid crystal as host. Experimental and theoretical analyses reveal that R/S-BDP molecules, endowed with double phosphine cores in axial chirality, offer a direct way for intramolecular electron transfer upon photoirradiation. This leads to the generation of radical ionic pairs, which subsequently trigger the donor-acceptor arrangement through intermolecular electron transfer, thereby resulting in stable radical emission. The extended photoactivated BDP-F exhibits a remarkably high quantum efficiency of 57.8%. Ultimately, the distinctive photo-responsive CPL radical luminescence has been successfully used for information displays and anti-counterfeiting.

One-Pot Synthesis of Acetylacetonate-Based Isomeric Phosphorescent Cyclometalated Iridium(III) Complexes via Random Cyclometalation: A Strategy for Excited-State Manipulation.

The excited-state manipulation of the phosphorescent iridium(III) complexes plays a vital role in their photofunctional applications. The development of the molecular design strategy promotes the creative findings of novel iridium(III) complexes. The current molecular design strategies for iridium(III) complexes mainly depend on the selective cyclometalation of the ligands with the iridium(III) ion, which is governed by the steric hindrance of the ligand during the cyclometalation. Herein, a new molecular design strategy (i.e., random cyclometalation strategy) is proposed for the effective excited-state manipulation of phosphorescent cyclometalated iridium(III) complexes. Two series of new and separable methoxyl-functionalized isomeric iridium(III) complexes are accessed by a one-pot synthesis via random cyclometalation, resulting in a dramatic tuning of the phosphorescence peak wavelength (∼57 nm) and electrochemical properties attributed to the high sensitivity of their excited states to the position of the methoxyl group. These iridium(III) complexes show intense phosphorescence ranging from the yellow (567 nm) to the deep-red (634 nm) color with high photoluminescence quantum yields of up to 0.99. Two deep-red emissive iridium(III) complexes with short decay lifetimes are further utilized as triplet emitters to afford efficient solution-processed electroluminescence with reduced efficiency roll-offs.

Isomer Engineering of Lepidine-Based Iridophosphors for Far-Red Hypoxia Imaging and Photodynamic Therapy.

The development of highly efficient cyclometalated phosphorescent iridium(III) complexes is greatly promoted by their rational molecular design. Manipulating the excited states of iridophosphors could endow them with appealing photophysical properties, which play vital roles in triplet state-related photofunctional applications (e.g., electroluminescence, photodynamic therapy, etc.). In general, the most effective approach for decreasing the emission energies of iridophosphors is to extend the π-skeleton of ligands. However, the π-extension strategy often results in decreased solubility, lower synthetic yield, decreased photoluminescence quantum yield, and so forth. In this work, a simple yet efficient strategy is proposed for the effective excited-state manipulation of 2-phenyllepidine-based iridophosphors. Surprisingly, dramatic tuning of phosphorescence wavelength (∼70 nm) is achieved by simply controlling the position of a single methoxyl substituent on these iridophosphors. An oxygen-responsive iridophosphor featuring far-red emission (660 nm), long emission lifetime (1.60 µs), and high singlet oxygen quantum yield (0.73) is employed to realize accurate oxygen sensing in vitro and in vivo, and it also shows efficient photodynamic therapy in cancer cells, making it a promising candidate for the efficient image-guided photodynamic therapeutic agent. This molecular design strategy clearly demonstrates the advantages of designing novel long-wavelength emissive iridophosphors without increasing the π-conjugation of the ligand.

Hsa_circ_0007494 suppresses prostate cancer progression via miR-616/PTEN axis.

Circular RNAs (circRNAs) are important players in prostate cancer (PCa) development and progression, but their detailed mechanisms have not been elucidated. Herein, hsa_circ_0007494 was suppressed in the PCa cell lines and tissues. This resulted in metastasis of tumors to the lymph node and predicted tumor stage. Functionally, overexpression of hsa_circ_0007494 inhibited the proliferation and invasive capacity of the cells in vitro and blocked the growth of tumors in vivo. Hsa_circ_0007494 functioned as a "molecular sponge" for miR-616 and hence upregulated the target of miR-616, PTEN. In addition, rescue assays revealed that PTEN silencing (or miR-616 mimics) blocked the tumor-suppressing effects of hsa_circ_0007494 overexpression on PCa progression. Together, our findings indicate that hsa_circ_0007494 suppresses PCa by forming a negative regulatory network including hsa_circ_0007494/miR-616/PTEN. Thus, hsa_circ_0007494 may be a treatment target for PCa.

miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion.

Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in non-small-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3'-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets.

Is Lipopolysaccharide-Induced Lipid Metabolism Disorder in Testis of Rats a Consequence of Plasma Lipid Changes?

Purpose: The systemic infection and inflammation can result in testes injury, whereas the exact mechanism is unknown. The lipid metabolism has a dual impact on controlling metabolism and inflammation, which is a potential pathway. The objective of this study was to determine if changes in plasma lipids during lipopolysaccharide (LPS)-induced systemic inflammation affect the dysregulation of testes lipid metabolism. Materials and Methods: LPS (5 mg/kg) was used to induce systemic inflammation in rats after a single intraperitoneal injection. After 4 weeks, the rats were sacrificed, and the serum and testes were used for laboratory measurements and histology examination. Plasma and testis were used for lipidomics analysis based the liquid chromatography-mass spectrometry. Spearman rank correlation analysis was used to compare the correlation of differential lipids in phospholipids, glycerolipids, and sphingolipids between testis and plasma. Results: LPS raised the levels of cytokines in serum and testis, decreased the activities of antioxidant enzymes, increased the levels of lipid peroxidation products, and damaged testis tissue. In testis and plasma, 146 and 401 differential lipids, mostly phosphatidylcholine, phosphatidylethanolamine an so on, were found in comparison to the control group. Correlation analysis produced a total of 2528 correlation coefficients, 1150 of which were P<0.05 and accounted for 45.49%. Conclusion: The changes of lipid composition and content in the testis are related to cytokine overload and oxidative stress. Testis lipid metabolism disorders caused by LPS-induced systemic inflammation are lack of a correlation with plasma lipid changes, and are likely owing to interference with the testis itself.

Tiam1 is associated with hepatocellular carcinoma metastasis.

We have previously demonstrated that overexpression of T lymphoma invasion and metastasis 1 (Tiam1) is correlated with poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we tried to further investigate the potential roles of Tiam1 in the progression of HCC in a larger set of samples. By detecting Tiam1 expression in 213 HCC patients, we observed that Tiam1 had a higher probability of being overexpressed in HCC patients with metastasis than those without metastasis (68.3% vs. 52.7%, p = 0.036). In addition, the cell line with high metastatic potential expressed more Tiam1 than did the cell line with low metastatic potential. Overexpression of Tiam1 was suggested to be significantly correlated with HCC metastasis. We stably upregulated Tiam1 expression in MHCC97L as well as knocked down Tiam1 expression in HCCLM6. We also investigated the effects of Tiam1 overexpression and knockdown on HCC cells proliferation, migration and invasion in vitro and on tumorigenicity and metastasis in vivo. Overexpression of Tiam1 increased proliferation, migration and invasion of MHCC97L cells, while knockdown of Tiam1 in HCCLM6 cells resulted in the reverse. In vivo functional studies showed upregulation of Tiam1 expression led to an enhancement of tumorigenicity and metastatic potential in mice. However, knockdown of Tiam1 expression exhibited nearly 2.2-fold retardation in tumor growth and great inhibition on tumor metastases. Our results indicate that Tiam1, as a metastasis-related gene, may contribute to HCC invasion and metastasis, and consequently, it may be a useful biomarker for therapeutic strategy and control in HCC treatment.

Nomogram for predicting survival of patients with gastric cancer and multiple primary malignancies: a real-world retrospective analysis using the Surveillance, Epidemiology and End Results database.

OBJECTIVES: Gastric cancer combined with multiple primary malignancies (GCM) is increasingly common. This study investigated GCM clinical features and survival time. METHODS: Patients with GCM and GC only (GCO) were selected from the Surveillance, Epidemiology and End Results (SEER) database. Survival was compared between GCM and GCO groups using propensity score matching. Then, the GCM group was divided into a training cohort and a validation cohort. These cohorts were used to establish a nomogram for survival prediction in patients with GCM. RESULTS: Survival time was significantly longer in the GCM group than in the GCO group. All-subsets regression was used to identify four variables for nomogram establishment: age, gastric cancer sequence, N stage, and surgery. The concordance index and time-dependent receiver operating characteristic curve indicated that the nomogram had favorable discriminative ability. Calibration plots of predicted and actual probabilities showed good consistency in both the training and validation cohorts. Decision curve analysis and risk stratification showed that the nomogram was clinically useful; it had favorable discriminative ability to recognize patients with different levels of risk. CONCLUSIONS: Compared with GCO, GCM is a relatively indolent malignancy. The nomogram developed in this study can help clinicians to assess GCM prognosis.

Efficient 1-(thiophen-2-yl)isoquinoline-based ionic iridophosphors with bulky counterions for solution-processed deep-red electroluminescence.

A pair of high-efficiency deep-red emissive ionic iridophosphors (Ira and Irb) showing high photoluminescence quantum yields (PLQYs) are rationally designed by using 1-(thiophen-2-yl)isoquinoline as the cyclometalating ligand. Two bulky tetraarylborate anions (tetraphenylborate and tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) are selected to improve their PLQYs in both solution and aggregated states, which enables efficient electroluminescence via a solution-processed approach. The variation of the tetraarylborate anions also aims to tune the photophysical properties of these deep-red emissive iridophosphors. Both ionic iridophosphors emit intense deep-red room-temperature phosphorescence in both solution and aggregated states. The phosphorescence spectra of both complexes are similar (630 nm with a shoulder emission of 686 nm) in CH2Cl2, originating from the same cationic species of the complexes. Both complexes show high PLQYs in CH2Cl2 (0.41 for Ira, 0.43 for Irb) and neat films (0.27 for Ira, 0.34 for Irb). Moreover, they serve as triplet emitters to evaluate their performance in solution-processed deep-red electroluminescent devices. The maximum external quantum efficiencies for the deep-red electroluminescence are 7.3% with an emission maximum of 649 nm for Ira, and 10.2% with an emission maximum of 635 nm for Irb, respectively, implying that they are good candidates for high-performance electroluminescence.

Impacts of climate and human activities on Daihai Lake in a typical semi-arid watershed, Northern China.

A rapid shrinkage of Daihai Lake was found in recent decades. The present study analyzed the characteristics of Daihai Lake shrinkage and quantified the contribution of climate and human activities. The results of Mann-Kendall- Sneyers test and moving t-test showed that there was an obvious mutation point of lake level in 2006 and the descending speed of Daihai Lake level post-2006 (-0.46m/a) was 3.22 times that of pre-2006 (-0.14m/a). The centroid of Daihai Lake moved 1365.18 m from southwest to northeast during 1989 ~ 2018 with an average speed of 47.08 m/a. The results of Mann-Kendall trend test revealed that the annual evaporation showed a significant downward trend with a rate of approximately -5.33 mm/a, while no significant trend was found in precipitation. Daihai lake water level showed a very weak relationship with evaporation (r = 0.078, p < 0.01) and precipitation (p>0.05) respectively. Daihai Lake was influenced by human activities mainly from land use/ land cover, building reservoirs, pumping groundwater and directly consuming Daihai Lake water by Daihai power plant (DHPP). It was thought-provoking that DHPP began to consume Daihai lake water in 2006, which was consistent with abrupt change of Daihai lake level. The proportion of human impact was fluctuating upward. Human factors were the main factor of lake water reduction in last 10 years and the 5-year average contribution of human activities to Daihai Lake shrinkage was more than 61.99%. More attention and economic support should be given to prevent the continuous shrinkage of Daihai Lake.

Influence of FDG-PET on computed tomography-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma.

PURPOSE: Assuming F-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET)/computed tomography (CT) to be more accurate in representing the true disease extent than CT alone, we prospectively designed this study to evaluate how the addition of FDG-PET influences CT-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma. PATIENTS AND METHODS: All patients underwent FDG-PET/CT simulation scans. For each patient, the gross tumor volume (GTV) was separately delineated with or without the addition of PET information and defined as GTV PET/CT and GTV CT, respectively. Corresponding planning target volumes (PTV) were generated for the GTV CT (PTV(CT)) and GTV PET/CT (PTV PET/CT). Three-dimensional conformal radiotherapy plans were separately created for PTV CT and PTV PET/CT. To assess the potential geographic miss of the PET/CT-based disease in CT-based treatment planning, the size and location of the GTV PET/CT, PTV(PET/CT), and PTV(CT) were analyzed, and the three-dimensional conformal radiotherapy plans created using the PTV CT were evaluated with the GTV PET/CT and PTV PET/CT information. RESULTS: A total of 43 patients were enrolled in this study. Distant metastasis was found in 4 patients with the addition of the PET information. The 39 patients without distant metastasis proceeded to three-dimensional conformal radiotherapy planning. Inadequate coverage of the GTV PET/CT and PTV PET/CT by the PTV CT occurred in 7 (18%) and 20 (51%) patients, respectively. This resulted in <95% of the GTV(PET/CT) and PTV PET/CT receiving >or=95% of the prescribed dose in 4 (10%) and 13 (33%) patients, respectively. CONCLUSIONS: The addition of FDG-PET information might influence CT-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma by altering the definition of the target volume, with the potential to avoid a geographic miss of true disease.

Influence of [18F] fluorodeoxyglucose positron emission tomography on salvage treatment decision making for locally persistent nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to evaluate the role of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) in influencing salvage treatment decision making for locally persistent nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 33 NPC patients with histologic persistence at nasopharynx 1 to 6 weeks after a full course of radiotherapy underwent both computed tomography (CT) and FDG-PET/CT simulation at the same treatment position. The salvage treatment decisions, with regard to the decision to offer salvage treatment and the definition of gross tumor volume (GTV), were made before knowledge of the FDG-PET findings. Subsequently the salvage treatment decisions were made again based on the FDG-PET findings and compared with the pre-FDG-PET decisions. RESULTS: All 33 patients were referred for salvage treatment in the pre-FDG-PET decision. After knowledge of the FDG-PET results, the decision to offer salvage treatment was withdrawn in 4 of 33 patients (12.1%), as no abnormal uptake of FDG was found at nasopharynx. Spontaneous remission was observed in repeat biopsies and no local recurrence was found in these 4 cases. For the remaining 29 patients, GTV based on FDG-PET was smaller than GTV based on CT in 24 (82.8%) cases and was greater in 5 (17.2%) cases, respectively. The target volume had to be significantly modified in 9 of 29 patients (31%), as GTV based on FDG-PET images failed to be enclosed by the treated volume in the salvage treatment plan performed based on GTV based on CT simulation images. CONCLUSION: Use of FDG-PET was found to influence the salvage treatment decision making for locally persistent NPC by identifying patients who were not likely to benefit from additional treatment and by improving accuracy of GTV definition in salvage treatment planning.

Dosimetric and clinical results of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma.

PURPOSE: To assess the dosimetric and clinical results of three-dimensional conformal radiotherapy (3D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). METHODS: A total of 86 patients with locally recurrent NPC were retreated with 3D CRT. The median prescribed dose was 68 Gy with 2 Gy per fractionation. Dosimetric quality was evaluated with dose distribution in planning target volume (PTV) and specified organs at risk (OAR), dose conformity index (CI) and dose homogeneity index (HI). The actuarial rate of local failure-free (LFF), overall survival (OS) and major late toxicities (MLT) were estimated with Kaplan-Meier method. Multivariate analysis for prognosis was performed using the Cox regression proportional hazards model. RESULTS: The mean dose to PTV averaged 66.8 Gy, and the dose to specified OAR was acceptable. The average value of CI and HI was 0.59 and 9.1%. The 5-year actuarial rate of LFF and OS was 71 and 40%, respectively. The 5-year actuarial incidence of MLT>or=Grade 3 and >or=Grade 4 were 100 and 49%, respectively. The major prognostic factors were T stage and the size of gross tumor volume (GTV). Advanced T stage and large GTV volume were associated with poor LFF and OS and high risk of MLT. CONCLUSION: The dosimetric quality of 3D CRT for locally recurrent NPC is generally excellent. A relatively high local control was achieved with this technique. However, the incidence of late toxicities were not found to decrease as originally expected. Early diagnosis of the recurrence and reasonable definition of the target volume are crucial to achieve a better outcome.

Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing.

AIM: To explore the impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines. METHODS: The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed. RESULTS: The alpha/ beta and repair half-time (T(1/2)) of HepG2 and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min, while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols. CONCLUSION: The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.

[Radiotherapeutic effect and prognosis of bulky exophytic cervical cancer].

OBJECTIVE: To retrospectively analyze the factors affecting the radiotherapeutic effects and prognosis of patients with bulky exophytic cervical cancer. METHODS: Sixty-four patients with bulky exophytic cervical cancer with a maximal diameter measuring 5 to 8 cm (mean 6.5 cm) were treated with a combined radiotherapy with external beam, interstitial, intracavitary irradiations. According to the FIGO staging system, 9 patients were classified as stage IIA, 19 as IIB, 5 as IIIA, and 31 as IIIB. The patients were restaged according to the same system based on the history records at the fourth week in the radiotherapy course. The cumulative survivals were analyzed with Kaplan-Meier method, and the factors influencing the prognosis including age, histology, maximal tumor diameter, stage before treatment and restage in radiotherapy were analyzed with Cox regression model. RESULTS: Restaging during radiotherapy classified 9 patients as stage I, 28 as IIA, 13 as IIB, 5 as IIIA, and 9 as IIIB. The 5-year overall survival rate was 81% and the 5-year relapse-free survival rate 75.8%. Multivariate Cox regression analyses identified the restage in radiotherapy as the only significant, independent prognostic factor for overall survival (P<0.01). CONCLUSIONS: Radiotherapy can achieve satisfactory results for patients with bulky exophytic cervical cancer. The stage before treatment is inaccurate and not indicative of the prognosis, but the restage in radiotherapy can serve as a significant and independent prognostic factor.

Simultaneous determination of nintedanib and its metabolite BIBF 1202 in different tissues of mice by UPLC-MS/MS and its application in drug tissue distribution study.

A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneous determine nintedanib and BIBF 1202 in mice plasma and tissue using carbamazepine as the internal standard (IS). Sample preparation was accomplished through a protein precipitation procedure with acetonitrile. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7µm) with the mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution at a flow rate of 0.40mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 540.3→113.1 for nintedanib, m/z 526.3→113.1 for BIBF 1202 and m/z 237.1→194.1 for IS, respectively. The linearity of this method was found to be within the concentration range of 1-1000ng/mL with a lower limit of quantification of 1.0ng/mL for each drug. Only 3.0min was needed for an analytical run. The inter-day and intra-day precision and accuracy of quality control (QC) samples, evaluated both in plasma and tissue homogenates, were all within 15%. The method was successfully applied to the pharmacokinetic and tissue distribution study of nintedanib and BIBF 1202 in mice after oral administration of nintedanib.

Three-dimensional conformal radiotherapy versus intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma.

PURPOSE: To compare the outcomes of three-dimensional conformal radiotherapy (3D-CRT) and intracavitary brachytherapy (ICBT) as salvage treatment for locally persistent nasopharyngeal carcinoma. METHODS AND MATERIALS: Between March 1994 and November 2001, a total of 117 patients with locally persistent nasopharyngeal carcinoma received salvage treatment for 2-8 weeks (median, 4 weeks) after a full course of conventional external beam RT. Of the 117 patients, 54 were salvaged with 3D-CRT (3D group) and 63 with ICBT (BT group). No statistically significant differences were found in the patient characteristics between the two groups (p >0.05). In the 3D group, the planning target volume for 3D-CRT was defined as the persistent disease plus a 5-mm margin; three to seven static conformal coplanar or noncoplanar portals were delivered for each fraction. The median salvage dose was 24 Gy (range, 18-38 Gy), with fraction size of 2.0 Gy/d. In the BT group, a median salvage dose of 20 Gy (range, 15-30 Gy) was delivered with a (192)Ir source, at 5 Gy/fraction, twice weekly. The brachytherapy dose was prescribed at a distance of 1 cm from the center of the surface as defined by the sources, irrespective of the extent of persistent disease. The actuarial rates of survival were estimated using the Kaplan-Meier method. Potential differences in the actuarial outcomes between groups were evaluated using the Mantel log-rank test. Multivariate analyses were performed with the Cox regression proportional hazards model. RESULTS: The 5-year actuarial rates of overall survival, disease-specific survival, and local failure-free survival for the 3D group and BT group were 64.50% vs. 55.78% (p = 0.33), 70.03% vs. 59.56% (p = 0.11), and 88.93% vs. 76.28% (p = 0.07), respectively. Subgroup analysis showed that the 5-year actuarial local failure-free survival rate of patients with initially diagnosed T3-T4 disease for the 3D group and BT group was 84.01% vs. 60.50% (p = 0.03). The incidence of Grade 3-4 late complications was comparable between the two groups. Multivariate analyses performed in the whole group showed that T stage at initial diagnosis and the salvage technique (3D-CRT or ICBT) were the statistically significant, independent prognostic factors for local failure-free survival (p = 0.00 and p = 0.02, respectively). CONCLUSION: 3D-CRT seemed to provide better local control than ICBT as a salvage treatment for locally persistent nasopharyngeal carcinoma, especially in patients with initially diagnosed T3-T4 disease. CT/MRI evaluation of the extent of persistent disease is recommended for technique selection of salvage RT. Patients should be cautioned about the potentially increased complications. The optional time for salvage treatment remains controversial.

Therapeutic effect of three-dimensional conformal radiotherapy on locally advanced pancreatic carcinoma.

OBJECTIVE: To evaluate the effects of the two conformal radiotherapy modalities in the treatment of locally advanced pancreatic carcinoma. METHODS: From October, 1998 to June, 2001, 67 patients with locally advanced pancreatic carcinoma received conformal radiotherapy (CRT). Vacuum cushions were applied to immobilize the patients before contrast CT scans, the treatment plans were simulated by three-dimensional treatment planning system. The patients were randomized into group A to receive a total dose of 45-54 Gy given in 8-12 fractions completed in 18-27 d and group B with a total dose of 45-54 Gy in 15-18 fractions within 20-25 d. RESULTS: The partial and complete pain relief rates of the two groups were 95.9% and 81.6%, respectively, one month after the completion of the radiotherapy, with a median survival of 12.5 months. The response rates of the patients and the 2-year overall survival rates in group A were 81.8% and 51.6%, respectively, and were 35.3% and 12.1% in group B. The low-dose fractionated CRT was superior than accelerated CRT. CONCLUSION: For patients with unresectable pancreatic cancer receiving low-dose fractionated CRT, a high dose targeted at the tumor can be given in a fraction and the normal surrounding tissues are exposed to low-dose radiation, to achieve good therapeutic effect with minimized adverse effects on normal tissues in relation to the exposure.

[CT findings and risk factor analysis of hepatic injury induced by three-dimensional conformal radiation therapy].

OBJECTIVE: To investigate the CT findings and define the risk factors for early hepatic injury induced by three- dimensional conformal radiation therapy in patients with primary liver cancer. METHOD: This study recruited 52 patients with primary liver cancer undergoing photon beam radiation at a total dose of 35 to 65 Gy (49.88+/-7.23 Gy) completed within 18 to 31 d. CT examinations were performed within 1 to 3 months after the completion of the therapy, and logistic regression was used to analyze the CT features of early hepatic injury, in an attempt to define the correlation of the injury occurrence with such factors as the patients' age, gender, treatment portal numbers, liver cirrhosis, transcatheter arterial embolization (TACE), postoperative recurrence, total radiation dose, target volume and fractional dose. RESULTS: Thirty-one (59.6%) patients showed CT features of hepatic injury, displayed as the area with hypodensity in consistency with the radiation coverage. The risk factors correlated to the injury occurrence included the total dose, target volume and fractional dose, but not the patients'age, gender, treatment portal number, liver cirrhosis, TACE, postoperative recurrence differences and radiation-induced hepatic injury. CONCLUSION: Early radiation-induced hepatic injury is related to fractional dose, total dose and target volume adopted in radiation therapy. Higher fractional dose, total irradiated dose and larger target volume may result in increased risk of injury.

[Risk factors of level Ib lymphadenopathy in nasopharyngeal carcinoma].

OBJECTIVE: To analyze the risk factors for level Ib lymph node enlargement on CT in patients with nasopharyngeal carcinoma (NPC) and provide clinical evidence for defining the indications of prophylactic level Ib irradiation. METHODS: A total of 435 newly diagnosed NPC patients receiving radiotherapy in Nanfang Hospital in the past 2 years were enrolled in this analysis. The correlations were analyzed with Logistic regression between level Ib lymphadenopathy and the clinical risk factors including T stage, N stage, diameter of level II lymph nodes, submandibular gland involvement, nasal cavity involvement, oropharyngeal involvement, and involvement of 4 or more lymphatic drainage regions. RESULTS: Univariate analysis showed that level Ib lymphadenopathy were positively correlated with N stage (P=0.023), submandibular gland involvement (P=0.045), and level II lymph node diameter (P<0.001). Multivariate Logistic regression analysis suggested a significant correlation only between the diameter of the level II lymph nodes and level Ib lymphadenopathy (P=0.013). CONCLUSION: Level Ib lymphadenopathy is positively correlated with the size of ipsilateral level II lymph nodes in NPC patients.