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.

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.

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.

[Association between single nucleotide polymorphism locus rs189037 in the promoter of ATM gene and nasopharyngeal carcinoma susceptibility in Cantonese].

OBJECTIVE: To evaluate the correlation between single nucleotide polymorphisms (SNP) in the promoter of ataxia-telangiectasia mutated (ATM) gene and the susceptibility of nasopharyngeal carcinoma in Cantonese. METHODS: A total of 176 NPC Cantonese NPC patients and 202 age-matched healthy controls were enrolled in this study. G/A genotyping of the SNP locus rs189037 in the promoter of ATM gene was performed by PCR and direct sequencing of the PCR products. RESULTS: The genotype frequency of heterozygote G/A was 50% (88/176) and 47.5% (96/202), and that of the homozygote variant A/A was 15.3% (27/176) and 18.3% (37/202) in NPC patients and healthy individuals, respectively. Statistics analysis revealed no evident correlations of the G/A and A/A genotypes to the clinical phenotypes of NPC in either NPC group or healthy control group (OR7equals;1.022, 95%CIequals;0.668-1.564 for G/A+A/A). Analysis after stratification by age and gender found no such correlations either. CONCLUSION: The genotype frequencies of SNP locus rs189037 in the promoter of ATM gene are similar between NPC patients and healthy subjects, suggesting that rs189037 is not related to the genetic susceptibility of NPC in Cantonese.

[Gefitinib enhances the radiosensitivity of nasopharyngeal carcinoma cell line CNE2 in vitro].

OBJECTIVE: To study the radiosensitizing effect of gefitinib on nasopharyngeal carcinoma cell line CNE2 in vitro. METHODS: Nasopharyngeal carcinoma cell line CNE2 was cultured in RP2MI 1640. MTT assay was performed to evaluate the cell proliferation changes in response to gefitinib treatment and the radiosensitizing effect of gefitinib. The cell survival curves and sensitive enhancement ratio (SERs) were obtained with a clonogenic assay. Flow cytometry analysis was applied to detect the cell cycle changes and cell apoptosis. RESULTS: MTT assay showed that cells exposed to gefitinib and radiation had a significantly lower survival ratio compared to the cells with radiation exposure only (0.582∓0.012 vs 0.398∓0.016, P=0.002), with a SER of 1.535∓0.134. The S phase cell percentage was significantly decreased and G(2)-M phase cells increased in gefitinib plus radiation group (P=0.000), suggesting a synergistic effect of gefitinib and radiation. CONCLUSION: Gefitinib can enhance the radiosensitivity of nasopharyngeal carcinoma CNE2 cells in vitro possibly by inhibiting cell proliferation, inducing cell apoptosis, and causing changes in the cell cycle distribution.

Impact of prolonged fraction delivery times simulating IMRT on cultured nasopharyngeal carcinoma cell killing.

PURPOSE: To determine the impact of prolonged fraction delivery times (FDTs) simulating intensity-modulated radiotherapy (IMRT) on cultured nasopharyngeal carcinoma (NPC) cell killing. METHODS AND MATERIAL: Cultured NPC cell lines CNE1 and CNE2 were used in this study. The biological effectiveness of fractionated irradiation protocols simulating conventional external beam radiotherapy and IMRT (FDT of 15, 36, and 50 minutes) was estimated with standard colony assay, and the differences in cell surviving fractions after irradiation with different protocols were tested by use of the paired t test. The impact degree of prolonged FDTs (from 8 to 50 minutes) on cell killing was also assessed by the dose-modifying factors, which were estimated by comparing the effectiveness of intermittently delivered 2 Gy with that of continuously delivered 1.5 to 2 Gy. RESULTS: The cell surviving fractions of both CNE1 and CNE2 after fractionated irradiation simulating IMRT were higher than those simulating conventional external beam radiotherapy (p < 0.05). The dose-modifying factors for a fraction dose of 2 Gy increased from 1.05 to 1.18 for CNE1 and from 1.05 to 1.11 for CNE2 with the FDT being prolonged from 15 to 50 minutes. CONCLUSIONS: This study showed that the prolonged FDTs simulating IMRT significantly decreased the cell killing in both CNE1 and CNE2 cell lines, and these negative effects increased with the FDT being prolonged from 15 to 50 minutes. These effects, if confirmed by in vivo and clinical studies, need to be considered in designing IMRT treatments for NPC.

[Determination of the repair half-time of human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and C666-1].

OBJECTIVE: To determine the repair half-time (T1/2), a speed parameter of sub-lethal damage repair (SLDR), of human nasopharyngeal carcinoma (NPC) cell lines CNE1, HONE1, C666-1 and CNE2. METHODS: A total radiation dose of 8 Gy divided into 4+4 Gy was delivered to the cell lines at the interval of 0 s, 15 s, 30 s, 1 h, 2 h, 4 h or 6 h. The cell survival fractions were determined using the standard cell clonogenic assay. The curves of the changes in the surviving cell fraction after a total dose of 8 Gy, as a function of the interval between the two doses of 4 Gy, were fitted manually, and the T1/2 of each cell line was calculated according to the curves. RESULTS: The T1/2 of CNE1, HONE1, C666-1 and CNE2 were 18 s, 22 s, 29 s and 27 s, respectively. CONCLUSION: The speed of SLDR of NPC cells is quite rapid, indicating that the fraction delivery time longer than 20 s might decrease the effect of radiotherapy.

[Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for massive primary liver cancer].

OBJECTIVE: To evaluate the outcomes of patients with unresectable massive primary liver cancer (PLC) receiving three-dimensional conformal radiotherapy (3-DCRT) combined with transcatheter arterial chemoembolization (TACE). METHODS: From January 2001 to December 2004, 84 patients with unresectable massive PLC (tumor size> or =10 cm) received 3-DCRT combined with TACE, including 49 cases in UICC/AJCC T(3) stage and 35 cases in T(4) stages. Lymph node metastasis was found in none of the patients, and portal vein tumor thrombosis (PVTT) was detected in 30 cases. Child-Pugh grade A of liver cirrhosis was present in 64 cases and grade B in 20 cases. The mean value of GTV was 705-/+430 cm(3) (170-2099 cm(3)). Following injections of fluorouracil and hydroxycamptothecine into the target artery of the tumor, the mixture of carboplatin, mitomycin (or pirarubicin) and super-liquefactive iodized oil was injected into the target artery. Gelatin sponge was used to embolize the artery. The procedure was repeated every 1.5-2 months according to the condition of the patients, and each patient received 1-3 such procedures. 3-DCRT was performed in all the patients, who received a total dose of 53.6-/+6.6 Gy (4-6 Gy per fraction at the interval of 48 h), and 3 fractions were given every week. RESULTS: Eight patients died in 3 months after 3-DCRT and were not evaluated. The total response rate (CR+PR) in these patients was 68.9% (51/74). The overall survival rates at 1, 2 and 3 years were 55.4%, 24.7% and 15.4%, respectively. T stage, GTV, PVTT and fraction size had no significant impact on the overall survival. Child-Pugh grade was found to have significant impact on the patients' survival (P=0.035, RR=2.440). CONCLUSION: 3-DCRT combined with TACE has definite therapeutic effect on advanced massive PLC, and Child-Pugh grade is an independent prognostic factor in such cases.

[The role of cell cycle arrest in radiosensitization of nasopharyngeal carcinoma cell line CNE1 by inhibiting ATM expression].

BACKGROUND & OBJECTIVE: Cell cycle regulation is one of the most important determinants to ionizing radiosensitivity of cells. ATM gene is closely related with DNA damage repair and cell cycle checkpoints control. We previously reported that suppressing ATM expression with antisense ATM RNA could enhance radiosensitivity of nasopharyngeal carcinoma (NPC) cell line CNE1. This study was to explore the involved changes of cell cycle and the mechanisms of cell cycle arrest. METHODS: ATM gene was constructed into retrovirus vector pDOR to form recombinant pDOR-atm. CNE1 cells were transfected with pDOR-atm (CNE1/pDOR-atm cells) or pDOR (CNE1/pDOR cells) and irradiated with X-ray. Cell cycle and cell apoptosis were detected by flow cytometry at different time points after irradiation. RESULTS: S phase arrest was detected at 1, 4, and 8 h after irradiation in both groups, and G2 arrest at 24, and 48 h, while no comparable G1 arrest and apoptosis were revealed. The mean percentage of S phase cells was lower, and G2 phase cells was higher in CNE1/pDOR-atm group than in CNE1/pDOR group (P<0.05). CONCLUSION: The mechanisms of cell cycle regulation in radiosensitized CNE1 cells by inhibiting ATM expression might be related with the decreased accumulation of S phase cells and increased accumulation of G2/M phase cells, while have no relationship with G1 arrest and apoptosis.

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.

[Radiosensitization of nasopharyngeal carcinoma cell line CNE1 by inhibiting the expression of ATM/PI3K functional region].

BACKGROUND & OBJECTIVE: It is reported that ATM gene is closely correlated to cellular radiosensitivity in several malignant tumors. Suppression of ATM protein expression leads to cellular radiosensitization. This study was to determine whether this effect also exists in nasopharyngeal carcinoma (NPC) cell line CNE1 by inhibiting the expression of ATM protein through antisense RNA of ATM/PI3K region, which is the most important functional fragment of ATM gene. METHODS: The recombinant pDOR-atm expressing antisense RNA of ATM/PI3K segment was constructed with retroviral vector pDOR. CNE1 cells were stably transfected with pDOR-atm by cationic liposome and named CNE1/pDOR-atm. Semi-quantitive RT-PCR was used to detect the level of ATM mRNA. Flow cytometry (FCM) was employed to analyze the percentage of positive cells and mean fluorescence density of protein expressing ATM. Cellular radiosensitivity was evaluated by colony survival assay (CSA) and linear-quadratic model in both CNE1/ pDOR-atm and control cells. RESULTS: The level of ATM mRNA index (RI) was 0.23+/-0.02 in CNE1/pDOR-atm group, and 0.51+/-0.03 in control group (P<0.05). The percentage of positive cells and mean fluorescence density of proteins expressing ATM were 70.8% and 1.81+/-0.12 in CNE1/pDOR-atm group, while 99.3% and 4.51+/-0.18 in control group(P<0.01). The expression of ATM mRNA and protein was inhibited by antisense RNA. The alpha value (one function from linear-quadratic model) of CNE1/pDOR-atm group was 0.40 Gy(-1), while it was 0.36 Gy(-1) in control group. The radiosensitizing ratio of surviving fraction at 2 Gy (SF(2)) was 3.0, indicating that antisense RNA group was more radiosensitive to X-ray than the controls. CONCLUSION: NPC cell line CNE1 could be radiosensitized by the down-regulation of ATM/PI3K expression.

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.

[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.

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.

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.