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Now that the debate about the safety and effectiveness of laparoscopic versus open surgery is over, attention has turned to innovations that can verify whether minimizing the impact of laparoscopy on the abdominal wall can further reduce pain, improve patient comfort, lead to superior cosmesis, and reduce morbidity. The aim of this study was to further explore the application value of totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction (NOSE) and to evaluate the short-term efficacy of transcolonic NOSE surgery for resecting specimens of ascending colon cancer. From January 2016 to May 2017, a retrospective study was conducted in Guangxi. Propensity score matching was used to minimize the bias from nonrandomized treatment assignment. Patients were followed up through May 2020. Forty-nine patients underwent totally laparoscopic right hemicolectomy with transcolonic NOSE and 116 patients laparoscopic right hemicolectomy with mini-laparotomy (ML) procedures at our institution. After propensity score matching, each group included 45 patients, and all covariate imbalances were alleviated. The transcolonic NOSE group and the ML group did not differ significantly in terms of baseline clinical characteristics. The transcolonic NOSE group was associated with a shorter time to first flatus (NOSE vs ML: 1.8 ±.5 vs 3.2 ±.8, P =.032), a shorter length of hospital stay (11.3 ± 2.5 days vs 13.0 ± 3.1 days, P =.034), a shorter time to first liquid intake (2.6 ±.8 vs 3.8 ±.9, P =.068), less pain (1.8 ±.8 vs 4.2 ±.7, P =.013), less analgesia requirement (6 [13.3%] vs 21 [46.7%], P =.001), and lower C-reactive protein levels on postoperative day 1 (3.6 ± 1.7 vs 8.2 ± 2.2, P =.001) and postoperative day 3 (NOSE 2.4 ± 1.4 vs M: 4.6 ± 1.7 [ P =.013]) than the ML group. The median follow-up was 28.4 months (interquartile range, 18.0-36.0). The 3-year overall survival rates were similar between the transcolonic NOSE group and the ML group. In total, laparoscopic right hemicolectomy with transcolonic specimen extraction appears to be safe for selected patients with ascending colon cancer as a minimally invasive surgery. [Display omitted] [ABSTRACT FROM AUTHOR]

• Retrospective surveillance on ILI samples identifies a S-OIV H3N2 (A/GD/277/H3N2/2017) which caused a spill-over infection in a young child. • Hemagglutination-inhibition test shows A/GD/277/H3N2/2017 is antigenically distinct from seasonal H3N2 viruses currently circulating in the human population. • A/GD/277/H3N2/2017 is a novel reassortant of EA-H1N1 and H3N2 previously circulating in swine in southern china. • Phylogenetic analysis shows A/GD/277/H3N2/2017-like virus caused another spill-over infection in Vietnam in 2010 suggesting the firm establishment of this swine lineage in Southeast Asia. [ABSTRACT FROM AUTHOR]

Abstract: Acid rain and inputs of acidic effluent can result in increased acidity in aquatic ecosystems, where it is known to have a significant impact and possibly, to cause the decline of some populations of aquatic organisms. In previous studies, intracellular acid-induced oxidative stress has been shown to cause DNA damage, and cooperatively activate the expression of the p53 gene. The acute effects of acidic environments on shrimp and fish have been widely studied. However, the molecular mechanism of acid-induced injury remains largely unknown. In this study, we examined the cellular responses of tilapia to acidic exposure-induced oxidative stress and antioxidant enzyme gene expression. Furthermore, we determined how acute acid stress activates the ATM–p53 signal pathway. We measured the upregulation of reactive oxygen species (ROS) production, the intracellular Ca2 + concentration ([Ca2 +]i), the tail DNA values, the malondialdehyde (MDA) level in the blood cells and the percentage of dead and damaged blood cells. Our results suggest that oxidative stress and DNA damage occurred in tilapia in conditions where the pH was 5.3. Apoptosis was detected by Hoechst staining, which was mainly associated with changes in cell viability. The parameters that we measured were related to acid-induced DNA damage, and all parameters changed in the blood cells through time. The effects of acute acid exposure (pH 5.3) on the expression of ATM, p53, p21, Bax, manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) were investigated in tilapia blood cells. The results showed that acute acid stress induced upregulation of ATM, p53 and p21, associated with increasing of DNA damage and apoptosis in blood cells. Additionally, the expression of Bax was slightly increased. Moreover, consensus p53-binding sequences were identified in tilapia MnSOD and GPx gene promoter regions and increased levels of ROS in the blood cells coincided with increased mRNA expression of p53, MnSOD and GPx. Therefore, it suggests that acid exposure-induced oxidative stress may cause DNA damage or apoptosis, and cooperatively activate ATM–p53 pathway, which may lead to the activation of p21 and regulate transcription of MnSOD and GPx. [Copyright &y& Elsevier]

Purpose: To review the literature regarding the role of radiotherapy (RT) in the treatment of patients with radiation-induced malignant gliomas (RIMGs). Methods and Materials: A PubMed search of English-language articles dealing with RIMG was performed, yielding 52 articles with 92 patients available for review. Results: Initial tumor types treated with RT included brain tumor in 37 patients (40%), acute lymphoblastic leukemia in 33 (36%), benign disease in 11 (12%), and other in 11 (12%). Median time from RT to development of an RIMG was 8.75 years (range, 2.5–61 years). The RIMG occurred within 10 years after RT in 81% of patients with acute lymphoblastic leukemia/lymphoma, 59% of patients with brain/other, and 18% of patients with benign conditions (p = 0.002). Type of RIMG was glioblastoma in 69 (75%) and anaplastic astrocytoma in 23 (25%). One-, 2-, and 5-year overall survival rates were 29.3%, 7.3%, and 0% for patients with glioblastoma and 59.7%, 30.3%, and 20.2% for patients with anaplastic astrocytoma. For the 85 patients with data regarding treatment for RIMG, 35 underwent reirradiation to a median dose of 50 Gy (range, 30–76 Gy). For patients undergoing reirradiation, 1-, 2- and 5-year overall survival rates were 58.9%, 20.5%, and 6.8%. For those not undergoing reirradiation, they were 15.1%, 3%, and 0% (p = 0.0009). Conclusions: The RIMG appeared earlier in patients treated for leukemia and lymphoma and latest for those treated for a benign condition. Patients who underwent reirradiation for RIMG have longer survival times compared with those not receiving RT. [Copyright &y& Elsevier]

Purpose: To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment. Methods: Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose. Results: Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. A variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations. Conclusion: Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions. [Copyright &y& Elsevier]

: PurposeTo report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC).: Methods and materialsA total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9–78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68–70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT.: ResultsThe treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V95-GTV) was 98.5%, and the dose encompassing 95% of GTV (D95-GTV) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3–13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%).: ConclusionThe improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome. [Copyright &y& Elsevier]

Objectives: To report prostate-specific antigen (PSA) bounce in patients treated with intensity-modulated radiotherapy (IMRT) alone. Previous studies have reported PSA bounce in prostate cancer patients treated with conventional radiotherapy, 3D conformal radiotherapy, and permanent seed brachytherapy. Methods: From January 1997 to July 2002, 102 patients with clinically localized prostate cancer were treated with IMRT alone. No patients received androgen ablation. PSA bounce was defined as a PSA increase of at least 0.4 ng/mL, followed by any PSA decrease. Biochemical failure was defined by both the American Society for Therapeutic Radiology and Oncology 1996 and 2006 consensus definitions. Results: The median follow-up was 76 months. The median length of time until the first PSA bounce was 13.6 months. Thirty-three patients (32.4%) had at least 1 PSA bounce, with 25 (24.5%) having 1 bounce; 6 (5.9%), 2 bounces; and 2 (2.0%), 4 bounces. PSA bounce was not significantly associated with biochemical no evidence of disease survival, clinical stage, pretreatment PSA, Gleason combined score, prostate planning target volume, PSA nadir, or mean dose to the prostate. The rate of PSA bounce in patients aged ≤ 70 and > 70 years was 44.4% and 22.8%, respectively (P = .032). Conclusions: Our patient series is the first report on PSA bounce in patients treated with IMRT. Our study confirms that the majority of patients with a bouncing PSA remain biochemically and clinically free of disease with extended follow-up. [Copyright &y& Elsevier]

Purpose: To identify pretreatment characteristics and radiotherapy parameters which may influence time interval to development of radiation-associated meningioma (RAM). Methods and Materials: A Medline/PUBMED search of articles dealing with RAM yielded 66 studies between 1981 and 2006. Factors analyzed included patient age and gender, type of initial tumor treated, radiotherapy (RT) dose and volume, and time interval from RT to development of RAM. Results: A total of 143 patients with a median age at RT of 12 years form the basis of this report. The most common initial tumors or conditions treated with RT were medulloblastoma (n = 27), pituitary adenoma (n = 20), acute lymphoblastic leukemia (n = 20), low-grade astrocytoma (n = 19), and tinea capitis (n = 14). In the 116 patients whose RT fields were known, 55 (47.4%) had a portion of the brain treated, whereas 32 (27.6%) and 29 (25.0%) had craniospinal and whole-brain fields. The median time from RT to develop a RAM or latent time (LT) was 19 years (range, 1–63 years). Male gender (p = 0.001), initial diagnosis of leukemia (p = 0.001), and use of whole brain or craniospinal field (p ≤ 0.0001) were associated with a shorter LT, whereas patients who received lower doses of RT had a longer LT (p < 0.0001). Conclusions: The latent time to develop a RAM was related to gender, initial tumor type, radiotherapy volume, and radiotherapy dose. [Copyright &y& Elsevier]

Purpose: The moyamoya syndrome is an uncommon late complication after radiotherapy (RT). Methods and Materials: A PubMed search of English-language articles, with radiation, radiotherapy, and moyamoya syndrome used as search key words, yielded 33 articles from 1967 to 2002. Results: The series included 54 patients with a median age at initial RT of 3.8 years (range, 0.4 to 47). Age at RT was less than 5 years in 56.3%, 5 to 10 years in 22.9%, 11 to 20 years in 8.3%, 21 to 30 years in 6.3%, 31 to 40 years in 2.1%, and 41 to 50 years in 4.2%. Fourteen of 54 patients (25.9%) were diagnosed with neurofibromatosis type 1 (NF-1). The most common tumor treated with RT was low-grade glioma in 37 tumors (68.5%) of which 29 were optic-pathway glioma. The average RT dose was 46.5 Gy (range, 22–120 Gy). For NF-1–positive patients, the average RT dose was 46.5 Gy, and for NF-1–negative patients, it was 58.1 Gy. The median latent period for development of moyamoya syndrome was 40 months after RT (range, 4–240). Radiation-induced moyamoya syndrome occurred in 27.7% of patients by 2 years, 53.2% of patients by 4 years, 74.5% of patients by 6 years, and 95.7% of patients by 12 years after RT. Conclusions: Patients who received RT to the parasellar region at a young age (<5 years) are the most susceptible to moyamoya syndrome. The incidence for moyamoya syndrome continues to increase with time, with half of cases occurring within 4 years of RT and 95% of cases occurring within 12 years. Patients with NF-1 have a lower radiation-dose threshold for development of moyamoya syndrome. [Copyright &y& Elsevier]

Purpose: Radiation-induced osteosarcomas (R-OS) have historically been high-grade, locally invasive tumors with a poor prognosis. The purpose of this study was to perform a comprehensive literature review and analysis of reported cases dealing with R-OS in the pediatric population to identify the characteristics, prognostic factors, optimal treatment modalities, and overall survival of these patients. Methods and Materials: A MEDLINE/PubMed search of articles written in the English language dealing with OSs occurring after radiotherapy (RT) in the pediatric population yielded 30 studies from 1981 to 2004. Eligibility criteria included patients <21 years of age at the diagnosis of the primary cancer, cases satisfying the modified Cahan criteria, and information on treatment outcome. Factors analyzed included the type of primary cancer treated with RT, the radiation dose and beam energy, the latency period between RT and the development of R-OS, and the treatment, follow-up, and final outcome of R-OS. Results: The series included 109 patients with a median age at the diagnosis of primary cancer of 6 years (range, 0.08–21 years). The most common tumors treated with RT were Ewing’s sarcoma (23.9%), rhabdomyosarcoma (17.4%), retinoblastoma (12.8%), Hodgkin’s disease (9.2%), brain tumor (8.3%), and Wilms’ tumor (6.4%). The median radiation dose was 47 Gy (range, 15–145 Gy). The median latency period from RT to the development of R-OS was 100 months (range, 36–636 months). The median follow-up after diagnosis of R-OS was 18 months (1–172 months). The 3- and 5-year cause-specific survival rate was 43.6% and 42.2%, respectively, and the 3- and 5-year overall survival rate was 41.7% and 40.2%, respectively. Variables, including age at RT, primary site, type of tumor treated with RT, total radiation dose, and latency period did not have a significant effect on survival. The 5-year cause-specific and overall survival rate for patients who received treatment for R-OS involving chemotherapy alone, surgery alone, and surgery plus chemotherapy was 17.3% and 17.3%, 56.6% and 50.3%, and 71.0% and 68.3%, respectively (p < 0.0001, log–rank test). Conclusion: The type of treatment for R-OS was the most significant factor for cause-specific and overall survival. Patients who develop R-OS should be aggressively treated, because the outcome is not as dismal as once thought. [Copyright &y& Elsevier]

Purpose: The advent of widespread prostate-specific antigen screening has resulted in more younger, potent men being diagnosed with early-stage, organ-confined prostate cancer amenable to definitive surgery. Nerve-sparing prostatectomy is a relatively new surgical advance in the treatment of prostate cancer. Very few data exist on the effect of postoperative radiotherapy (RT) on erectile function after nerve-sparing prostatectomy. They are based on conventional techniques using moderate doses of radiation, 45–54 Gy. Intensity-modulated RT (IMRT) is becoming more widespread because it allows dose escalation with increased sparing of the surrounding normal tissue. We investigated the effect of postprostatectomy, high-dose IMRT on patients’ erectile function.Methods and Materials: A review of patient records found 51 patients treated between April 1998 and December 2000 with IMRT after unilateral or bilateral nerve-sparing prostatectomy. The pathologic disease stage in these patients was T2 in 47.4% and T3 in 52.6%. Postoperatively, 4 patients received hormonal ablation consisting of one injection of Lupron Depot (30 mg) 2 months before RT. The median age was 65 years (range 46–77) at the time of RT. The prescribed dose was 64 Gy (range 60–66). The mean dose was 69.6 Gy (range 64.0–72.3). Erectile function was assessed before and after RT by questionnaires. Sexual potency was defined as erectile rigidity adequate for vaginal penetration.Results: Of the 51 patients, 18 (35.3%) maintained their potency and 33 (64.7%) became impotent after nerve-sparing prostatectomy. Patients who underwent bilateral nerve-sparing prostatectomy had higher rates of postoperative potency than did those who underwent unilateral nerve-sparing surgery (72.2% vs. 27.8%; p = 0.025). The follow-up for the entire group was 19.5 months. All 18 patients (100%) who were potent postoperatively remained potent after RT. The median follow-up for the 18 potent patients was 27.2 months, significantly longer than that of the impotent group, 13.0 months (p <0.001).Conclusion: This is the first report on the effects of dose-escalated IMRT on men who have undergone nerve-sparing prostatectomy. Despite the high dose (mean dose 69.6 Gy) to the prostate bed and nerves, postoperative IMRT had no negative effect on erectile function for the patients who remained potent after nerve-sparing prostatectomy. Longer term follow-up and a larger cohort of patients are warranted to confirm these findings. [Copyright &y& Elsevier]

The implementation of intensity-modulated radiation therapy (IMRT) is the result of advances in imaging, radiotherapy planning technologies, and computer-controlled linear accelerators. IMRT allows both conformal treatment of tumors and conformal avoidance of the surrounding normal structures. The first patient treated with Peacock IMRT at Baylor College of Medicine took place in March 1994. To date, more than 1500 patients have been treated with IMRT; more than 700 patients were treated for prostate cancer. Our experience in treating prostate cancer with IMRT was reviewed. Patient and prostate motions are important issues to address in delivering IMRT. The Vac-Lok bag-and-box system, as well as rectal balloon for immobilization of patient and prostate gland, respectively, are employed. Treatment planning also plays a very important role. IMRT as a boost after conventional external beam radiotherapy is not our treatment strategy. To derive maximal benefits with this new technology, all patients received full course IMRT. Three separate groups of patients receiving (1) primary IMRT, (2) combined radioactive seed implant and IMRT, and (3) post-prostatectomy IMRT were addressed. Overall, toxicity profiles in these patients were very favorable. IMRT has the potential to improve treatment outcome with dose escalation while minimizing treatment-related toxicity. [Copyright &y& Elsevier]

3D graphene networks (3DGN) as reinforcement for epoxy composites have attracted intense attention, while the interfacial adhesion with the matrix is still a key issue. With respect to the impact between interfacial wettability for graphene sheets in 3DGN and the performance for epoxy-based composites, 3DGNs prepared by self-assembly method, have been carbonized in N 2 at heat treatment temperature between 220 and 800 °C, and then incorporated into epoxy by resin transfer molding method. Polyving akohol serving as cross-linking agent is converted to amorphous carbon during the annealing process, which effectively interconnects and enhances graphene sheet-sheet welding. When the carbonization temperature is 400 °C (3DGN-4), epoxy contact angles decrease from 100.2° to 56.7°, and 3DGN-4/epoxy composites are increased significantly 84% and 56% in compressive and flexural strength, respectively. In the meantime, this 3DGN serving as radiation protection of epoxy composites has been investigated for the first time. The electron spin resonance detection shows that 3DGN could act as radical scavenger in the gamma irradiation environment, and mechanical performance retention rate of 3DGN-4/epoxy composites is above 92% after gamma irradiation, which is higher than that of epoxy resin. Therefore, the designed 3D graphene networks can be considered as promising candidates for improving both the mechanical properties and radiation resistance of epoxy composites. [ABSTRACT FROM AUTHOR]

To enhance photocatalysis and recycling abilities of catalyst simultaneously, novel microstructure in which TiO 2 nanoparticles were semi-wrapped in carbon nanofibers (CNFs) was proposed and produced successfully. Betaine was employed as a foaming agent to drive the TiO 2 nanoparticles to migrate from inner space to the surface of CNFs gradually under the function of calcination. Various characterizations were used to research the surface and crystal evolution process of TiO 2 and CNFs, and the semi-wrapped microstructure of TiO 2 @CNFs was well built up when the composites were carbonized at 800 °C. TiO 2 was immobilized stably on CNFs while exposed partly to air distinctively. This unique semi-wrapped structure endowed the composites with strong interfacial interaction between TiO 2 and CNFs, and the exposed section of TiO 2 provided sufficient reaction sites for organic dyes. Notably, photocatalytic degradation ratio of Rhodamine B in the first time reached 98.2% and even remained 95.4% after being recycled for 5 times under the irradiation of ultraviolet light, indicating that the photocatalysis and recycling abilities were obviously strengthened simultaneously compared with other counterparts reported in literature. [ABSTRACT FROM AUTHOR]

For the poor capacity utilization and insufficient cyclability of TiO 2 /C anodes for lithium-ion batteries, we synthesized branch-like TiO 2 @mesoporous carbon nanofibers (TiO 2 @MCNFs) as free-standing anodes via electrospinning technique, hydrothermal treatment and a subsequent carbonization process, where anatase TiO 2 branches were densely embedded on the mesoporous carbon nanofiber trunks. Due to the copious highly-exposed TiO 2 nanocrystal lattices on the branch except for the trunk support, the abundant intrinsic crystal channels for fluent Li + transportation, and the interlaced carbon nanofiber framework with a high structural integrity and mechanical flexibility, the branch-like TiO 2 @MCNFs composites presented a superior initial discharge capacity of 1932 mAhg −1 and an excellent reversible capacity of ∼617 mAhg −1 after 100 cycles. And compared with those of the reported TiO 2 /C electrodes, the initial discharge capacity and reversible capacity of the branch-like TiO 2 @MCNFs composites increased by ∼2 times and ∼50%, respectively. Hence, the unique architecture of the branch-like TiO 2 @MCNFs composites and their superior electrochemical performances may provide new insights for the development of better host materials for practical lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To analyse the outcomes and to evaluate the prognostic factors involved in the re-irradiation of locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT). Materials and methods: A retrospective analysis of 239 NPC patients with local recurrence who were re-irradiated with IMRT between 2001 and 2008 was conducted. The distribution of disease re-staging was 5.4% for stage I, 18.4% for stage II, 29.7% for stage III and 46.4% for stage IV. Cisplatin-based chemotherapy was administered to 117 patients (49.0%) in addition to the IMRT. Results: The mean D95 and the V95 of the gross tumour volume (GTV) were 66.78Gy and 98.61%, respectively. The mean dose to the GTV was 70.04Gy (61.73–77.54Gy). The 5 year overall survival, local recurrence-free survival, distant metastasis-free survival and disease-free survival were 44.9, 85.8, 80.6 and 45.4%, respectively. In a univariate analysis, patient age, recurrent T (rT), recurrent N (rN), recurrent stage, tumour volume, mean dose and mean fractional dose of the GTV were significant prognostic factors for overall survival. In a multivariate analysis, only patient age, rN stage, recurrent stage, mean fractional dose and tumour volume remained significant for overall survival. Conclusions: Re-irradiation using IMRT is available to improve local tumour control and to prolong patients’ survival. A smaller tumour volume, higher fractional dose, younger patient ages, lower rN0 stage and early recurrent stage are all independent prognostic factors for overall survival of recurrent NPC. It is of clinical importance to select the appropriate recurrent NPC cases for salvage re-irradiation by IMRT. [Copyright &y& Elsevier]

Abstract: A series of azulene-based derivatives were synthesized as potent inhibitors for receptor tyrosine kinases such as FMS-like tyrosine kinase 3 (FLT-3). Systematic side chain modification of prototype 1a was carried out through SAR studies. Analogue 22 was identified from this series and found to be one of the most potent FLT-3 inhibitors, with good pharmaceutical properties, superior efficacy, and tolerability in a tumor xenograft model. [Copyright &y& Elsevier]

Abstract: A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure–activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice. [Copyright &y& Elsevier]

Abstract: The ROS production, the percentage of dead and damaged haemocytes, the DNA Olive Tail Moment (OTM) value and the gene expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx) and thioredoxin (TRx), were studied in the Pacific white shrimp, Litopenaeus vannamei, when exposed to acute pH stress. The increased ROS production in haemocytes and the increased OTM value in both the haemocytes and the hepatopancreas cells suggest that oxidative damage occurred in shrimp exposed to pH 5.6 and pH 9.3, with apoptosis, mainly being associated with excess Ca2+influx and changes in cell viability. Acid and alkaline pH-induced DNA damage was time dependent in the haemocytes and the hepatopancreas cells. The concentration of intracellular free calcium [Ca2+] i after different pH treatments increased significantly over time, reaching its highest concentration after 12 h, but decreasing gradually to normal levels after 24 h. The [Ca2+] i content in shrimp cells when exposed to pH 9.3 and pH 5.6 for 12 h had increased by 58%–81%, compared with exposure to pH 7.4 (control). In addition, the gene expression of cMnSOD, CAT, GPx and TRx in the hepatopancreas of L. vannamei was induced by acid and alkaline pH stress, although there were differences in the expression response with respect to the duration of induction and the different pH treatments (acid or alkaline). Our results show that acidic or alkaline-induced oxidative stress may cause DNA damage, and cooperatively activate expression of CAT, GPx and TRx mRNA. Calcium ions appear to be important in mediating shrimp responses to pH stress. [Copyright &y& Elsevier]

Abstract: The result of reirradiation in recurrent T1 (rT1) nasopharyngeal carcinoma (NPC) is unsatisfactory. We sought to study the efficacy and complications of endoscopic microwave coagulation therapy (MCT) in salvaging rT1 NPC after primary radiotherapy. Between August 1994 and April 2005, 55 patients with rT1 NPC were treated with endoscopic MCT. With a median follow-up of 102.1months, 52 of 55 patients are still alive. Five patients had local failure after retreatment. The overall survival and local progression-free survival were 100% (95% CI, 99.4% to 100%) and 94.5% (95% CI, 94.1% to 94.9%) at 2years, respectively, and 93.6% (95% CI, 93.5% to 94.4%) and 90.7% (95% CI, 90.2% to 91.2%) at 5years. The common complications of endoscopic MCT were mild postoperative pain and headache. Nasopharyngeal necrosis was transient in one patient and subsided in 1month. Endoscopic MCT achieved significant survival and tumour control without severe complications in selective rT1 NPC. [Copyright &y& Elsevier]

[Display omitted] • The abnormal local and long-range FCD in MCI compared with HCs. • The reversed FCD was found in MCI after treatments of acupoint-related moxibustion. • After moxibustion treatment, the MoCA scores of MCI were improved. Mild cognitive impairment (MCI) is a general neurodegenerative disease. Moxibustion has been shown to have remarkable effect on cognitive improvement, however, less is known about the effect of moxibustion on MCI and its underlying neural mechanism. This study aimed to investigate the ameliorative brain network in MCI after treatments of acupoint-related moxibustion. Resting-state functional MRI were derived from 47 MCI patients and 30 healthy controls (HCs). Patients were randomized as Tiaoshen YiZhi (TSYZ, n = 27) and sham (SHAM, n = 20) acupoint moxibustion groups. Functional connectivity density (FCD) method and repeated-measures two-way analysis of variance (ANOVA) were performed to ascertain the interaction effects between groups (TSYZ and SHAM) and time (baseline and post-treatment). Abnormal FCD was examined between baseline and post-treatment in TSYZ and SHAM groups, respectively. Compared with HCs, MCI showed altered FCD in the middle frontal cortex (MFC), inferior frontal cortex, temporal pole, thalamus and middle cingulate cortex. After moxibustion treatment in MCI, 1) a significant time-by-groups interaction was observed in the medial prefrontal cortex (mPFC); 2) abnormal long-range FCD (lrFCD) in the mPFC and MFC were modulated in TSYZ group; 3) significantly improved clinical symptoms; 4) changed lrFCD in the MFC was significantly negatively correlated with the increased Montreal Cognitive Assessment scores in TSYZ group. These imaging findings suggest that treatments of acupoint-related moxibustion could improve lrFCD in certain regions related to self-related cognitive and decision making. Our study might promote understanding of MCI neural mechanisms and expand the clinical application of moxibustion in MCI. [ABSTRACT FROM AUTHOR]

• An new multi-task learning framework is devised for differential diagnosis of subjective cognitive decline and mild cognive impairment. • The proposed multi-task learning algorithm combines functional and structural brain information. • The proposed method can discover the most disease-related brain regions and their connectivity. • The extensive experiments demonstrate good classification performance against competing techniques. Early diagnosis and intervention of mild cognitive impairment (MCI) and its early stage (i.e., subjective cognitive decline (SCD)) is able to delay or reverse the disease progression. However, discrimination between SCD, MCI and healthy subjects accurately remains challenging. This paper proposes an auto-weighted centralised multi-task (AWCMT) learning framework for differential diagnosis of SCD and MCI. AWCMT is based on structural and functional connectivity information inferred from magnetic resonance imaging (MRI). To be specific, we devise a novel multi-task learning algorithm to combine neuroimaging functional and structural connective information. We construct a functional brain network through a sparse and low-rank machine learning method, and also a structural brain network via fibre bundle tracking. Those two networks are constructed separately and independently. Multi-task learning is then used to identify features integration of functional and structural connectivity. Hence, we can learn each task's significance automatically in a balanced way. By combining the functional and structural information, the most informative features of SCD and MCI are obtained for diagnosis. The extensive experiments on the public and self-collected datasets demonstrate that the proposed algorithm obtains better performance in classifying SCD, MCI and healthy people than traditional algorithms. The newly proposed method has good interpretability as it is able to discover the most disease-related brain regions and their connectivity. The results agree well with current clinical findings and provide new insights into early AD detection based on the multi-modal neuroimaging technique. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4–48 months). The mean percentages of DR+CD8+ T cells were increased at all timepoints up to 8 months. The mean percentages of DR+CD4+ T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer. [Copyright &y& Elsevier]

Abstract: The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Lok™ bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2 × 2-cm field size. The dose beyond the interface recovered quickly and the dose reductions due to air cavity were 50%, 28%, 11%, and 1% at 2, 5, 10, and 15 mm, respectively, from the distal air-tissue interface. Evaluating the dose profiles of the more clinically relevant situation revealed the dose at air-tissue interface was approximately 15% lower in comparison to that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, there was only an 8% and 5% differential, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal with or without the air cavity. The median follow-up was 31.3 months. Rectal toxicity profile was very favorable: 81% (94/116) patients had no rectal complaint while 10.3% (12/116), 6.9% (8/116), and 1.7% (2/116) had grade 1, 2, and 3 toxicity, respectively. There was no grade 4 rectal toxicity. DVH analysis revealed that none of the patients had more than 25% of the rectum receiving 70 Gy or greater. Rectal balloon has rendered anterior rectal wall sparing by its dosimetric effects. In addition, it has reduced rectal volume, especially posterior and lateral rectal wall receiving high-dose radiation by rectal wall distension. Both factors may have contributed to decreased rectal toxicity achieved by IMRT despite dose escalation and higher than conventional fraction size. The findings have clinical significance for future very high-dose escalation trials whereby radiation proctitis is a major limiting factor. [Copyright &y& Elsevier]

Purpose: In situ cytotoxic gene therapy can potentially trigger a systemic immune response, which could impact occult metastatic disease. We are currently conducting three clinical trials using in situ adenoviral vector mediated herpes simplex virus–thymidine kinase (HSV-tk) gene delivery followed by the HSV-tk prodrug ganciclovir (GCV) or valacyclovir (VCV). This study evaluates the systemic T-cell response after gene therapy in each trial.Methods and materials: The study protocol included three separate clinical trials in the Baylor Prostate Cancer SPORE Program: Trial A gene therapy in prostate cancer patients failing radiotherapy (36 patients), Trial B neoadjuvant gene therapy in pre–radical prostatectomy patients (22 patients), and Trial C gene therapy in combination with radiotherapy for prostate cancer (27 patients). Heparinized blood was collected at the time of vector injection and at selected intervals afterward. A complete blood count was performed, and peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting after labeling with dual color–labeled antibody pairs.Results: The pretreatment mean percentage of activated CD8+ T cells (DR+CD8+ T cells) was 12.23%, 16.72%, and 14.09% (Trials A, B, and C, respectively). Two weeks posttreatment, this increased to 22.87%, 26.15%, and 39.04% (Trials A, B, and C, respectively), and these increases were statistically significant (p = 0.0188, p = 0.0010, p < 0.0001, respectively). The increase of DR+CD8+ T cells was significantly larger in Trial C than in Trial A (p = 0.0044) or Trial B (p = 0.0288). Total CD8+ T cells significantly increased at 2 weeks posttreatment in Trial B and C (p = 0.0013, p = 0.0004, respectively). Interestingly, only in Trial C were significant increases in activated CD4+ T cells seen at 2 weeks (p = 0.0035).Conclusions: This is the first report of systemic T-cell responses after HSV-tk+GCV/VCV gene therapy under three clinical trial conditions. There was an increase in activated CD8+ T cells in the peripheral blood after vector injection, suggesting the potential for activation of components of cell-mediated immune response in all trial conditions. The addition of radiotherapy to in situ gene therapy seems to further increase the total CD8+ T cells and activated CD4+ T cells. [Copyright &y& Elsevier]

: PurposeThere is an evolving role for combining radiotherapy (RT) with gene therapy in the management of prostate cancer. However, the clinical results of this combined approach are much needed. The preliminary results addressing the safety of this Phase I-II study combining RT and gene therapy (adenovirus/herpes simplex virus-thymidine kinase gene/valacyclovir with or without hormonal therapy) in the treatment of prostate cancer have been previously reported. We now report the prostate-specific antigen (PSA) response and biopsy data.: Methods and materialsThis trial was composed of three separate arms. Arm A consisted of low-risk patients (Stage T1-T2a, Gleason score <7, pretreatment PSA <10 ng/mL) treated with combined RT-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated RT. They also received adenovirus/herpes simplex virus-thymidine kinase/valacyclovir gene therapy. Arm B consisted of high-risk patients (Stage T2b-T3, Gleason score >6, pretreatment PSA level >10 ng/mL) treated with combined RT-gene therapy and hormonal therapy (luteinizing hormone-releasing hormone agonist [30-mg Lupron, 4-month depot] and an antiandrogen [flutamide, 250 mg t.i.d. for 14 days]). Arm C consisted of patients with Stage D1 (positive pelvic lymph nodes) who received the same regimen as Arm B with the addition of 45 Gy to the pelvic lymphatics. PSA determination and biopsy were performed before, during, and after treatment. The American Society for Therapeutic Radiology and Oncology consensus definition (three consecutive rises in PSA level) was used to denote PSA failure.: ResultsFifty-nine patients (29 in Arm A, 26 in Arm B, and 4 in Arm C) completed the trial. The median age was 68 years (range, 39–85 years). The median follow-up for the entire group was 13.5 months (range, 1.4–27.8 months). Only Arm A patients were observed to have an increase in PSA on Day 14. The PSA then declined appropriately. All patients in Arm A (median follow-up, 13.4 months) and Arm B (median follow-up, 13.9 months) had biochemical control at last follow-up. Three patients in Arm C (with pretreatment PSA of 335, 19.6, and 2.5 ng/mL and a combined Gleason score of 8, 9, and 9 involving all biopsy cores) had biochemical failure at 3, 3, and 7.7 months. Two patients had distant failure in bone and 1 patient in the para-aortic lymph nodes outside the RT portal. Six to twelve prostate biopsies performed in these 3 patients revealed no evidence of residual carcinoma. In Arm A, biopsy showed no evidence of carcinoma in 66.7% (18 of 27), 92.3% (24 of 26), 91.7% (11 of 12), 100% (8 of 8), and 100% (6 of 6) at 6 weeks, 4 months, 12 months, 18 months, and 24 months after treatment, respectively. In Arm B, no evidence of carcinoma on biopsy was noted in 96% (24 of 25), 90.5% (19 of 21), 100% (14 of 14), 100% (7 of 7), and 100% (2 of 2), respectively, in the same interval after treatment.: ConclusionThis is the first reported trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of RT by combining it with in situ gene therapy. The initial transient PSA rise in the Arm A patients may have been a result of local immunologic response or inflammation elicited by in situ gene therapy. Additional investigation to elucidate the mechanisms is needed. Hormonal therapy may have obliterated this rise in Arm B and C patients. The biopsy data were encouraging and appeared to show no evidence of malignancy earlier than historical data. Combined RT, short-course hormonal therapy, and in situ therapy appeared to provide good locoregional control but inadequate systemic control in patients with positive pelvic lymph nodes. Longer term use of hormonal therapy in addition to gene therapy and RT has been adopted for this group of patients to maximize both locoregional and systemic control. [Copyright &y& Elsevier]

: PurposeA pilot study was designed to evaluate the safety and efficacy of a novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the study was to combine the potential radiobiologic advantage of hypofractionation to GBM with a highly conformal radiotherapeutic technique. The study was designed to measure the acute and chronic morbidity of patients treated with this regimen, response of GBM to the treatment, overall survival, and time to disease progression after therapy completion.: Methods and materialsTwenty eligible patients were accrued between February 1999 and May 2000 for the study. All patients had Karnofsky performance scores of ≥70. All patients were treated with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease, residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy daily fractions to surrounding edema. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity scores.: ResultsOf the 20 patients, 18 were evaluated for outcome. The median time to disease progression was 6 months after RT completion. The median overall survival was 7 months after treatment completion. All recurrences were within 2 cm of the operative bed. Neurotoxicity during therapy was minimal, with all patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity, manifesting as brain necrosis requiring surgical reexcision. The survival of the 3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases was the result of tumor recurrence, with no mortality resulting from brain necrosis.: ConclusionThis regimen of hypofractionated intensity-modulated RT did not improve the time to disease progression or overall survival compared with historical experience using conventional fractionation. However, the treatment duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit in certain subsets of patients. This treatment regimen demonstrated a greater incidence of brain necrosis requiring surgical intervention; however, the 3 patients experiencing this toxicity had longer survival times. Future investigation may be useful to determine which fraction size may be optimal for GBM when highly conformal RT is used in the adjuvant setting. [Copyright &y& Elsevier]

: PurposeThe intensity-modulated radiation therapy (IMRT) treatment planning system generates tightly constricted isodose lines. It is very important to define the margins that are acceptable in the treatment of prostate cancer to maximize the dose escalation and normal tissue avoidance advantages offered by IMRT. It is necessary to take into account subclinical disease and the potential for extracapsular spread. Organ and patient motion as well as setup errors are variables that must be minimized and defined to avoid underdosing the tumor or overdosing the normal tissues. We have addressed these issues previously. The purpose of the study was twofold: to quantify the radial distance of extracapsular extension in the prostatectomy specimens, and to quantify differences between the pathologic prostate volume (PPV), CT-based gross tumor volume (GTV), and planning target volume (PTV).: Methods and materialsTwo related studies were undertaken. A total of 712 patients underwent prostatectomy between August 1983 and September 1995. Pathologic assessment of the radial distance of extracapsular extension was performed. Shrinkage associated with fixation was accounted for with a linear shrinkage factor. Ten patients had preoperative staging studies including a CT scan of the pelvis. The GTV was outlined and volume determined from these CT scans. The PTV, defined as GTV with a 5-mm margin in all dimensions, was then calculated. The Peacock inverse planning system (NOMOS Corp., Sewickley, PA) was used. The PPV, GTV, and PTV were compared for differences and evaluated for correlation.: ResultsExtracapsular extension (ECE) (i.e., prostatic capsular invasion level 3 [both focal and established]) was found in 299 of 712 patients (42.0%). Measurable disease extending radially outside the prostatic capsule (i.e., ECE level 3 established) was noted in 185 of 712 (26.0%). The median radial extension was 2.0 mm (range 0.50–12.00 mm) outside the prostatic capsule. As a group, 20 of 712 (2.8%) had extracapsular extension of more than 5 mm. In the volumetric comparison and correlation study of the GTV and PTV to the PPV, the average GTV was 2 times larger than the PPV. The average PTV was 4.1 times larger than the PPV.: ConclusionsThis is the largest series in the literature quantitatively assessing prostatic capsular invasion (i.e., the radial extracapsular extension). It is the first report of a comparison of PPV to CT-planned GTV and PTV. Using patient and prostate immobilization, 5 mm of margin to the GTV in this study provided sufficient coverage of the tumor volume based on data gathered from 712 patients. In the absence of prostate immobilization, additional margins of differing amounts depending on the technique employed would have to be placed to account for target, patient, and setup uncertainties. The large mean difference between CT-based estimates of the tumor volume and target volume (GTV+PTV) and PPV added further evidence for adequacy of tumor coverage. Target immobilization, setup error, and coverage of subclinical disease must be addressed carefully before successful implementation of IMRT to maximize its ability to escalate dose and to spare normal tissue simultaneously and safely. [Copyright &y& Elsevier]

: PurposeTo evaluate the predictors of xerostomia in the treatment of head-and-neck cancers treated with intensity-modulated radiation therapy (IMRT), using the simultaneous modulated accelerated radiation therapy (SMART) boost technique. Dosimetric parameters of the parotid glands are correlated to subjective salivary gland function.: Methods and materialsBetween January 1996 and June 2000, 30 patients with at least 6 months follow-up were evaluated for subjective xerostomia after being treated definitively for head-and-neck cancer with the SMART boost technique. Threshold limits for the ipsilateral and contralateral parotid glands were 35 Gy and 25 Gy, respectively. Dosimetric parameters to the parotid glands were evaluated. The median follow-up time was 38.5 months (mean 39.9 months). The results of the dosimetric parameters and questionnaire were statistically correlated.: ResultsXerostomia was assessed with a 10-question subjective salivary gland function questionnaire. The salivary gland function questionnaire (questions 1, 2, 3, 4, 6, and 9) correlated significantly with the dosimetric parameters (mean and maximum doses and volume and percent above tolerance) of the parotid glands. These questions related to overall comfort, eating, and abnormal taste. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands.: ConclusionsQuestions regarding overall comfort, eating, and abnormal taste correlated significantly with the dosimetric parameters of the parotid glands. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Dosimetric sparing of the parotid glands improved subjective xerostomia. IMRT in the treatment of head-and-neck cancer can be exploited to preserve the parotid glands and decrease xerostomia. This is feasible even with an accelerated treatment regimen like the SMART boost. More patients need to be evaluated using IMRT to identify relevant dosimetric parameters. [Copyright &y& Elsevier]

Purpose: Two major treatment options are available for patients with acoustic neuroma, microsurgery and radiosurgery. Our objective was to compare these two treatment modalities with respect to tumor growth control, hearing preservation, development of cranial neuropathies, complications, functional outcome, and patient satisfaction.Methods and Materials: To compare radiosurgery with microsurgery, we analyzed 96 patients with unilateral acoustic neuromas treated with Leksell Gamma Knife or microsurgery at Memorial Hermann Hospital, Houston, Texas, between 1993 and 2000. Radiosurgery technique involved multiple isocenter (1–30 single fraction fixed-frame magnetic resonance imaging) image-based treatment with a mean dose prescription of 14.5 Gy. Microsurgery included translabyrinthine, suboccipital, and middle fossa approaches with intraoperative neurophysiologic monitoring. Preoperative patient characteristics were similar except for tumor size and age. Patients undergoing microsurgery were younger with larger tumors compared to the radiosurgical group. The tumors were divided into small <2.0 cm, medium 2.0–3.9 cm, or large >4.0 cm. Median follow-up of the radiosurgical group was longer than the microsurgical group, 48 months (3–84 months) vs. 24 months (3–72 months).Results: There was no statistical significance in tumor growth control between the two groups, 100% in the microsurgery group vs. 91% in the radiosurgery group (p > 0.05). Radiosurgery was more effective than microsurgery in measurable hearing preservation, 57.5% vs. 14.4% (p = 0.01). There was no difference in serviceable hearing preservation between the two groups. Microsurgery was associated with a greater rate of facial and trigeminal neuropathy in the immediate postoperative period and at long-term follow-up. The rate of development of facial neuropathy was significantly higher in the microsurgical group than in the radiosurgical group (35% vs. 0%, p < 0.01 in the immediate postsurgical period and 35.3% vs. 6.1%, p = 0.008, at long-term follow-up). Similarly, the rate of trigeminal neuropathy was significantly higher in the microsurgical group than in the radiosurgical group (17% vs. 0% in the immediate postoperative period, p < 001, and 22% vs. 12.2%, p = 0.009, at long-term follow-up). There was no significant difference in exacerbation of preoperative tinnitus, imbalance, dysarthria, dysphagia, and headache. Patients treated with microsurgery had a longer hospital stay (2–16 days vs. 1–2 days, p < 0.01) and more perioperative complications (47.8% vs. 4.6%, p < 0.01) than did patients treated with radiosurgery. There was no correlation between the microsurgical approach used and postoperative symptoms. There was no difference in the postoperative functioning level, employment, and overall patient satisfaction. There was no correlation between the radiation dose, tumor size, number of isocenters used, and postoperative symptoms in the radiosurgical group.Conclusion: Radiosurgical treatment for acoustic neuroma is an alternative to microsurgery. It is associated with a lower rate of immediate and long-term development of facial and trigeminal neuropathy, postoperative complications, and hospital stay. Radiosurgery yields better measurable hearing preservation than microsurgery and equivalent serviceable hearing preservation rate and tumor growth control. [Copyright &y& Elsevier]

Purpose: To assess the safety and efficacy of intensity-modulated radiation therapy (IMRT) in the treatment of intracranial meningioma.Methods and Materials: Forty patients with intracranial meningioma (excluding optic nerve sheath meningiomas) were treated using IMRT with the NOMOS Peacock system between 1994 and 1999. Twenty-five patients received IMRT after surgery either as adjuvant therapy for incomplete resection or for recurrence, and 15 patients received definitive IMRT after presumptive diagnosis based on imaging. Thirty-two patients had skull base lesions, and 8 had nonskull base lesions. The prescribed dose ranged from 40 to 56 Gy (median 50.4 Gy) at 1.71 to 2 Gy per fraction, and the volume of the primary target ranged from 1.55 to 324.57 cc (median 20.22 cc). The mean dose to the target ranged from 44 to 60 Gy (median 53 Gy). Follow-up ranged from 6 to 71 months (median 30 months). Acute and chronic toxicity were assessed using Radiation Therapy Oncology Group (RTOG) morbidity criteria and tumor response was assessed by patient report, examination, and imaging. Overall survival, progression-free survival, and local control were calculated using the Kaplan-Meier method.Results: Cumulative 5-year local control, progression-free survival, and overall survival were 93%, 88%, and 89%, respectively. Two patients progressed after IMRT, one locally and one distantly. Each was treated with IMRT after multiple recurrences of benign meningioma over many years. Both were found to have malignant meningioma at the time of relapse after IMRT, and it is likely their tumors had already undergone malignant change by the time IMRT was given. Defined normal structures generally received a significantly lower dose than the target. The most common acute central nervous system (CNS) toxicity was mild headache, usually relieved with steroids. One patient experienced RTOG Grade 3 acute CNS toxicity, and 2 experienced Grade 3 or higher late CNS toxicity, with one possible treatment-related death. No toxicity was observed with mean doses to the optic nerve/chiasm up to 47 Gy and maximum doses up to 55 Gy.Conclusion: IMRT is a promising new technology that is safe and efficacious in the primary and adjuvant treatment of intracranial meningiomas. A history of local aggression may indicate malignant degeneration and predict a poorer outcome. Toxicity data are encouraging, but the potential for serious side effects exists, as demonstrated by one possible treatment-related death. Larger cohort and longer follow-up are needed to better define efficacy and late toxicity of IMRT. [Copyright &y& Elsevier]

Purpose: The combination of cisplatin chemotherapy and radiation therapy for the treatment of medulloblastoma has been shown to cause significant ototoxicity, impairing a child’s cognitive function and quality of life. Our purpose is to determine whether the new conformal technique of intensity-modulated radiation therapy (IMRT) can achieve lower rates of hearing loss by decreasing the radiation dose delivered to the cochlea and eighth cranial nerve (auditory apparatus).Patients and Methods: Twenty-six pediatric patients treated for medulloblastoma were retrospectively divided into two groups that received either conventional radiotherapy (Conventional-RT Group) or IMRT (IMRT Group). One hundred thirteen pure-tone audiograms were evaluated retrospectively, and hearing function was graded on a scale of 0 to 4 according to the Pediatric Oncology Group’s toxicity criteria. Statistical analysis comparing the rates of ototoxicity was performed using Fisher’s exact test with two-tailed analysis.Results: When compared to conventional radiotherapy, IMRT delivered 68% of the radiation dose to the auditory apparatus (mean dose: 36.7 vs. 54.2 Gy). Audiometric evaluation showed that mean decibel hearing thresholds of the IMRT Group were lower at every frequency compared to those of the Conventional-RT Group, despite having higher cumulative doses of cisplatin. The overall incidence of ototoxicity was lower in the IMRT Group. Thirteen percent of the IMRT Group had Grade 3 or 4 hearing loss, compared to 64% of the Conventional-RT Group (p < 0.014).Conclusion: The conformal technique of IMRT delivered much lower doses of radiation to the auditory apparatus, while still delivering full doses to the desired target volume. Our findings suggest that, despite higher doses of cisplatin, and despite radiotherapy before cisplatin therapy, treatment with IMRT can achieve a lower rate of hearing loss. [Copyright &y& Elsevier]

With a high theoretical specific and typical self-healing mechanism, Sn 4 P 3 alloy has been widely concerned as an anode material for sodium-ion batteries (SIBs). The mechanism is attributed to a reversible conversion reaction combined with an alloy reaction. Essentially, Sn nanoparticles act as an electronic channel to activate the P component. Meanwhile, P and Na 3 P play a matrix to partially restore the degradation and aggregation of the alloy. Nevertheless, pure Sn 4 P 3 inevitably shortens the cycle life due to volume expansion. Herein, the puffed rice hard carbon (HC) with loose structure within the temperature range from 800 °C to 1400 °C is used to tightly wrap the alloy via a simple ball milling. The structurally stable Sn 4 P 3 @HC composites improve the electrochemical performance of SIBs. At 1000 °C, the composites show an excellent reversible capacity of 430 mA h g−1 at 100 mA g−1 over 100 cycles, with an elevated rate capability of 260 mA h g−1 even at 3.0 A g−1, and a high capacity of 312 mA h g−1 after 400 cycles at 1.0 A g−1. This work not only testifies a superior design of HC and alloy which synergistically stabilize the electrochemical performance of SIBs, but also provides a simple, efficient, and easy-to-scale coating method for active materials. Image 1 • Structurally stable Sn 4 P 3 particles coated with HC are prepared by ball milling. • The structure and d -spacing of HC formed at different temperatures are investigated. • The Sn 4 P 3 @HC composites exhibit excellent electrochemical performances. • The co-storage mechanism of self-healing Sn 4 P 3 and HC is researched. [ABSTRACT FROM AUTHOR]

Introduction: A program combining in situ gene therapy and intensity-modulated radiation therapy (IMRT) was implemented for the treatment of prostate cancer because the complementary mechanisms of cytotoxicity may have an enhanced efficacy. The in situ gene therapy comprised of adenoviral vector mediated Herpes Simplex Virus-thymidine kinase (AdHSVtk) + valacyclovir (VCV). We are currently conducting clinical trials using this approach. This study explores long-term immune responses following combined radio-gene therapy compared to gene therapy as mono-therapy.Methods: The study design included two separate clinical trials in the Baylor Prostate Cancer SPORE Program: Trial A gene therapy in combination with IMRT for prostate cancer (31 patients) and Trial B gene therapy as mono-therapy for local recurrent prostate cancer after failing initial radiotherapy (36 patients). Heparinized blood was collected at the time of vector injection and at selected intervals afterward until 12 months. Peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting (FACS) after the incubation with dual color labeled antibody pairs: CD45/CD14, CD3/CD19, CD3/CD8, CD3/CD4, CD8/HLA-DR, CD4/HLA-DR, CD3/HLA-DR, and CD3/CD56+CD16.Results: The pre-treatment mean percentage of activated CD8+ T cells (DR+CD8+ T cells) was 14.7% and 12.2% (Trials A and B, respectively). Two weeks after the vector injection, this increased to 31.7% and 21.9% (Trials A and B, respectively), and these increases were statistically significant (P < 0.0001 and P = 0.0188, respectively). Only in Trial A were significant increases seen at 4 weeks, 12 weeks, 4 months, 6 months, 8 months and 10 months (P < 0.0001, P = 0.0002, 0.0464, 0.0016, 0.0125 and 0.0354, respectively). In addition, activated CD4+ T cells were noted to increase significantly after the vector injection from 2 weeks till 12 months in Trial A only. (P = 0.0013 and 0.0069, respectively).Conclusions: This is the first report of long-term systemic immune responses following radio-gene therapy compared to gene therapy as mono-therapy. We present evidence showing long-term (up to 12 months) systemic T cell responses to two consecutive AdHSVtk injections during combination in situ gene therapy and IMRT for prostate cancer. These results suggest the potential for sustained activation of cell-mediated immune responses and may have enhanced activities against cancer. This combined approach may maximize tumor control, both local-regional and systemic through radio-gene therapy induced cytotoxicity and anti-tumor immunity.Molecular Therapy (2006) 13, S18–S18; doi: 10.1016/j.ymthe.2006.08.057 [ABSTRACT FROM AUTHOR]