Improved Dosimetry with Daily Online Adaptive Radiotherapy for Cervical Cancer: Waltzing the Pear.

AIMS: Standard of care radiotherapy for locally advanced cervical cancer includes large margins to ensure the uterocervix remains within the treatment fields over the course of treatment. Daily online cone-beam adaptive radiotherapy corrects for interfractional changes by adjusting the plan to match the target position during each treatment session, thus allowing for significantly reduced clinical target volume (CTV) to planning target volume (PTV) margins. We hypothesise that reduced margins from daily online adaptive radiotherapy will reduce organ at risk dose without compromising target coverage. MATERIALS AND METHODS: Ten patients with cervical cancer (stage IIB-IIIC2) were treated with definitive chemoradiation using daily online cone-beam adaptive radiotherapy in 25-27 fractions. Initial and all adapted treatment plans were generated with CTV to PTV margins versus standard of care image-guided radiotherapy (IGRT) plans as follows: cervix/uterus/gross tumour volume (0.5 versus 1.5 cm), parametria/vagina (0.5 versus 1.0 cm) and nodal chains and gross nodes (0.5 versus 0.5 cm). IGRT plans were created and copied to synthetic computed tomography scans and contours generated from each daily adapted fraction. The dosimetry of each clinically treated online adapted fraction was compared with emulated IGRT plans. Statistical significance was defined as P < 0.05. RESULTS: Daily online cone-beam adaptive radiotherapy significantly improves bowel bag dosimetry compared with IGRT, with a reduction in V40 by an average of 91.3 cm3 [V40 (-6.2%) and V45 (-6.1%)]. The daily adapted plans showed significant improvements in bladder and rectum [V40 (-25.2% and -36.0%) and V30 (-9.7% and -17.1%), respectively]. Additionally, bone marrow had a significantly reduced dose [V10 (-2.7%) and V20 (-3.3%)]. Daily online cone-beam adaptive radiotherapy improved uterocervix CTV coverage and reduced hotspots compared with IGRT [D95% (+1.6%) and Dmax (-0.9%)]. CONCLUSIONS: Reduced CTV to PTV margins achievable with daily online adaptive radiotherapy improves organ at risk dosimetry and target coverage when compared with standard of care IGRT for locally advanced cervical cancer. The clinical impact of improved dosimetry is currently undergoing investigation.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Genetic alterations in primary melanoma in Taiwan.

BACKGROUND: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. OBJECTIVES: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. METHODS: We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. RESULTS: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. CONCLUSIONS: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

[Effect of overexpression of apoptosis-stimulating protein 2 of p53 on activation and apoptosis of hepatic stellate cells induced by transforming growth factor-ß1 and its mechanism].

Objective: To study the effect of apoptosis-stimulating protein 2 of p53 (ASPP2) on the activation and apoptosis of hepatic stellate cells induced by transforming growth factor-ß1 (TGF - ß1), and to explore the role of autophagy in this process. Methods: Mouse hepatic stellate cells were primarily isolated and cultured with green fluorescent protein (GFP) expressing empty vector adenovirus (Ad-GFP) and ASPP2 expressing adenovirus (Ad-ASPP2) for 12 h by transfection kit, and then treated with TGF-ß1 (10ng/ml) for 24 h. The experiments were grouped as follows: control group: green fluorescent protein (GFP) expressing empty vector adeno (Ad-GFP); experimental group 1: transfected with Ad-GFP and added with TGF-ß1; experimental group 2: transfected with Ad-ASPP2 and induced by TGF-ß1. Western blot and quantitative fluorescence PCR were used to detect the expression of ASPP2, α-smooth muscle actin (SMA). At the same time, autophagy was determined by microtubule-associated protein 1 light chain 3-ß (LC3). Autophagy and apoptosis of MHSc were observed by immunocytochemistry and RNA interference (RNAi). Multiple pairwise-comparisons between the mean of groups was performed by one-way ANOVA. Results: The relative expression of α-SMA mRNA in mHSC of TGF-ß1 + Ad-GFP group (16.83 ± 2.41) was significantly higher than Ad-GFP group (3.62 ± 0.56) (P < 0.05), while the relative expression of α-SMA mRNA (4.22 ± 0.48) in TGF-ß1 + Ad-GFP group was significantly lower than TGF-ß1 + Ad-GFP group (P < 0.05). The expression of α-SMA protein in each group was consistent with mRNA expression. The proportion of mHSC autophagy in TGF-ß1 + Ad-GFP group (80%) was significantly higher than Ad-GFP group (35%); however, there was no statistically significant difference between the two groups. The proportion of mHSC autophagy in TGF-ß1 + Ad-ASPP2 group was 42%, which was significantly lower than TGF-ß1 + Ad-GFP group, but the apoptotic rate was significantly increased. Cells were simultaneously treated with autophagy inhibitors 3-MA and TGF-ß1. The level of autophagy was not statistically significantly different from that of TGF-ß1 + Ad-ASPP2 group, but the apoptotic rate was increased. In addition, the RNAi group added with ASPP2 had increased autophagy (LC3-II/LC3-I) than control RNAi group, and the rate of apoptosis was significantly decreased. Conclusion: Overexpression of ASPP2 can alleviate the activation of mHSC and promote the apoptosis of HSC by inhibiting autophagy, so as to alleviate liver fibrosis.

Jagged2 promotes cancer stem cell properties of triple negative breast cancer cells and paclitaxel resistance via regulating microRNA-200.

OBJECTIVE: To investigate the role of Jagged2 in triple negative breast cancer (TNBC) and its underlying mechanism. PATIENTS AND METHODS: Breast cancer tissues of patients diagnosed with TNBC in Fujian Medical University Affiliated MinDong Hospital from January 2015 to September 2017 were selected. TNBC patients were divided into the paclitaxel-resistant group (n=34) and non-resistance group (n=11). Jagged2 expression in paclitaxel-resistant group and non-resistance group before and after treatment was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR), respectively. After Jagged2 knockdown in paclitaxel-resistant MDA-MB-231 cells (MDA-MB-231/TXR), expression of CD44+CD24-ESA+ subset was detected by flow cytometry. MicroRNA-200 expression was detected after Jagged2 knockdown in MDA-MB-231/TXR cells. RESULTS: Jagged2 was highly expressed in paclitaxel-resistant TNBC tissues and cells. Jagged2 expression was found to be associated with cancer stem cell (CSC) properties of TNBC cells. Knockdown of Jagged2 inhibited CSC properties and paclitaxel resistance, whereas upregulated microRNA-200 expression. The inhibited CSC properties and paclitaxel resistance induced by Jagged2 knockdown were reversed by microRNA-200 knockdown. CONCLUSIONS: Jagged2 maintains CSC properties of TNBC cells and paclitaxel resistance via regulating microRNA-200.

Factors Determining Physical and Mental Quality of Life of Living Kidney Donors in Taiwan.

BACKGROUND: Living-donor kidney transplantation has a positive influence on recipients' life expectancy and improves quality of life for patients with end-stage renal disease compared with dialysis patients. Evaluation of the physical and mental quality of life for donors can promote positive perceptions about donation and help potential donors in their decision-making process. The aim of this study was to explore the predictive factors of quality of life for living kidney donors. METHODS: A cross-sectional and descriptive design was used, and the study was conducted from January to July 2013. The donors were a convenience sample of 34 participants who had undergone kidney transplant surgery >1 year earlier. RESULTS: The results showed that kidney donors had a low to moderate physical and mental quality of life. Multiple regression analysis revealed that financial concerns and anxiety explained 27.8% of the total variance of quality of life in the physical component. Anxiety and paid work explained 61.4% of the total variance of quality of life in the mental component. CONCLUSIONS: After renal transplantation, living kidney donors experienced low to moderate quality of life. Because donors are family members (siblings, sons or daughters, spouses, or parents), monthly family income is a significant issue that influences both the decision to donate and quality of life after transplantation. Our findings suggest that pre-transplantation assessment must include social workers as part of the health care team to evaluate the impact of a donor's financial status on post-transplantation quality of life.

Impact of mTOR Inhibitors on Cancer Development in Kidney Transplantation Recipients: A Population-Based Study.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. METHODS: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. RESULTS: During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). CONCLUSIONS: The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.

Increased intrahepatic quasispecies heterogeneity correlates with off-treatment sustained response to nucleos(t)ide analogues in e antigen-positive chronic hepatitis B patients.

Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate the relationship between intrahepatic quasispecies heterogeneity and the NAs off-treatment outcomes in a prospective cohort. Eighteen HBeAg-positive patients with chronic hepatitis B who achieved the cessation criteria underwent liver biopsy, and stopped treatment thereafter. Patients were followed up prospectively for 1 year. The reverse transcriptase (RT) gene of intrahepatic hepatitis B virus (HBV) was cloned and sequenced. Intrahepatic quasispecies heterogeneity and specific gene mutations were analysed using bioinformatic methods. Ten patients achieved sustained response, and eight patients developed viral relapse. The intrahepatic quasispecies Shannon entropy and nucleotide diversity within either RT or the surface (S) region of patients with sustained response were significantly higher (p < 0.05) than those of patients who had a viral relapse. Intrahepatic quasispecies Shannon entropy at the nucleotide level predicted the sustained off-treatment response (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites and N-glycosylation mutations within the S region were found in patients with sustained response than in the patients with viral relapse (p < 0.01). Most of the positive selection sites in patients with sustained response were located in reported HLA-I-restricted or HLA-II-restricted epitopes. Intrahepatic quasispecies heterogeneity at the end of treatment was correlated with off-treatment outcomes in HBeAg-positive patients with chronic hepatitis B. More immune escape mutations were found within the S region in patients with sustained response. The higher intrahepatic quasispecies heterogeneity indicated a more robust immune control over HBV, which in turn maintained a sustained response after withdrawal of NAs.

Abnormal perfusion in patellofemoral subchondral bone marrow in the rat anterior cruciate ligament transection model of post-traumatic osteoarthritis: a dynamic contrast-enhanced magnetic resonance imaging study.

OBJECTIVE: Although anterior cruciate ligament (ACL) injury is a well-recognized risk factor for developing knee post-traumatic osteoarthritis (PTOA), the process in the patellofemoral (PF) joint after ACL injury is still under-researched. Our aim was to investigate the perfusion changes in PF subchondral bone marrow in the rat ACL transection (ACLX) model of PTOA using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DESIGN: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group): a normal control group and groups receiving ACLX and sham-surgery, respectively, in the right knee. Perfusion parameters in the patellar and femoral subchondral bone marrows of all rats were measured on DCE-MRI at 0, 4, 8, and 16 weeks after respective treatment. After the last MRI at week 16, the rats were sacrificed and their right knees were harvested for histologic examination. In addition, to observe the long-term histologic change in PF joints, 9 additional rats (n = 3 in each group) were included and sacrificed at week 32 for histologic examination. RESULTS: In the ACLX group vs the sham and control groups, the perfusion parameters were significantly changed in both patellar and femoral subchondral bone marrows at week 16. Histologic examination revealed cartilage defects in ACLX rats at 32 weeks after surgery. CONCLUSIONS: These data point to a possible functional relationship between subchondral bone marrow perfusion abnormalities and cartilage breakdown in PTOA. Moreover, the perfusion parameters derived from DCE-MRI can potentially serve as biomarkers of early OA.

Hypoxia inducible factor 2α/insulin-like growth factor receptor signal loop supports the proliferation and Oct-4 maintenance of mouse germline stem cells.

Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α(-/-)) decreases both expression of Oct-4 and PGC number in genital ridge. Hypoxia is known to stabilize HIF-2α protein from proteasomal degradation. However, little is known about the hypoxia-associated endocrinal signaling in HIF-2α expression. The current work demonstrates a role for an endocrine insulin-like growth factor-I receptor (IGF-IR)-PI3K/Akt-mTOR-HIF-2α regulatory loop in the proliferation and Oct-4 maintenance of PGC-like alkaline phosphatase positive mouse germline stem cells (AP(+)GSCs). We found that hypoxia greatly increased the cell proliferation and the levels of nuclear Oct-4/HIF-2α protein of AP(+)GSCs. The hypoxic-AP(+)GSCs presented stronger stemness ability for germ cell differentiation than normoxic, with expressions of c-KIT (differentiation germ cell marker), VASA (differentiation germ cell marker) and SCP3 (meiotic marker) using a renal capsule transplantation assay. Meanwhile, hypoxia significantly increased the expression levels of secreted-IGF-I and IGF-IR. The IGF-I dose dependently increased the HIF-2α expression levels in AP(+)GSCs; and, the inhibition of IGF-IR by RNA interference (shIGF-IR) or LY294002 (PI3K inhibitor)/Rapamycin (mTOR inhibitor) effectively suppressed the IGF-I- and/or hypoxia-induced HIF-2α and Oct-4 expression, suggesting that the IGF-IR and its downstream Akt/mTOR signaling are involved in the IGF-I/hypoxia effects. Additionally, knockdown of HIF-2α dramatically suppressed Oct-4 and IGF-IR protein levels in AP(+)GSC cells. In conclusion, the present study demonstrates a regulatory loop of IGF-IR-PI3K/Akt-mTOR-HIF-2α in proliferation and Oct-4 maintenance of PGC-like AP(+)GSCs under hypoxia. This finding provides insights into the niche endocrinology underlying early germ cell development.

Investigation of pulsed low dose rate radiotherapy using dynamic arc delivery techniques.

There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min⁻¹. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent cancers, which can be delivered using dynamic arc delivery techniques with ten full arcs and an effective dose rate of 6.7 ± 4.0 cGy min⁻¹.

Survival benefits of metabolic syndrome among older men aged 75 years and over in Taiwan.

BACKGROUND: Metabolic syndrome (MetS) was common in the elderly, but its prognostic significance in older old population remained unclear. The main purpose of this study was to evaluate the survival impact of MetS among older men aged 75 and over in Taiwan. METHODS: From 2008, residents aged 75 years and older of Banciao Veterans Home were invited for study and were followed for 3 years. All participants received history taking, physical examinations, and laboratory tests. Mortality was determined by Veteran Affairs Death Registry, which was linked to the National Death Registry. RESULTS: Overall, 680 men (mean age: 82.5±4.7 years) were enrolled for study and the prevalence of MetS was 31.6%. During the follow-up period, 140 (20.6%) participants died, and the causes of death included infectious diseases (62, 9.1%), cardiovascular disease (37, 5.4%), cancer (20, 2.9%), and others (21, 3.1%). MetS subjects had a significantly higher prevalence of hypertension, diabetes mellitus, and having higher body mass index, waist circumferences, systolic blood pressure, fasting blood glucose, serum triglyceride and lower HDL-C level than non-MetS subjects. However, MetS subjects were less likely to die during study period (16.3% vs. 22.6%, P=0.059). Multivariate logistic regression showed that older age (OR:1.04, 95% C.I.: 1.00-1.08, P=0.04), diabetes mellitus (OR: 2.10, 95% CI: 1.34-3.30, P=0.001) were independent risk factors for mortality; and serum total cholesterol and triglyceride were protective factors (OR: 0.99, 95% CI: 0.99-1.00, P=0.037 for cholesterol; OR: 0.99, 95% CI: 0.99-1.00, P=0.013 for triglyceride). Adjusted for age, diabetes mellitus, serum levels of total cholesterol, and triglyceride, MetS played a potential trend of survival benefits among study subjects (HR: 0.71, 95% CI: 0.45-1.12, P=0.144). CONCLUSIONS: The prevalence of MetS among men aged 75 years and over was 31.6%, and the 3-year mortality rate was 20.6%. Older age, diabetes mellitus, lower serum cholesterol and lower serum triglyceride were independent risk factors for mortality. Further investigation is needed to clarify the prognostic impact of MetS in older adults.

Radiolabeled nucleosides for predicting and monitoring the cancer therapeutic efficacy of chemodrugs.

Uncontrolled cell proliferation is an important hallmark of cancer. Cancer treatment with cytostatic chemodrugs usually results in insignificant changes in tumor size, and thus limits the applications of anatomical imaging modalities for determining the therapeutic efficacy. Positron emission tomography (PET) imaging with cell proliferation probes to assess the clinical outcome during or soon after treatment is becoming acceptable. At present, monitoring DNA synthetic pathways with radiolabeled nucleoside probes that are essential for cell proliferation has been considered a more specific approach to predict tumor response. Among the four nucleosides, thymidine analogues, such as (18)F-FLT, have undergone years of development for clinical practice, while cytidine, adenosine and guanosine analogues receive less attention. Recently, several literatures have demonstrated that PET imaging with radiolabeled cytidine and adenosine analogues may have potential to evaluate immune response after chemotherapy, and may enable the prognosis forecast. In this review, we summarize the results of recent preclinical and clinical studies regarding using radiolabeled nucleoside analogues for predicting and monitoring tumor response in cancer treatment. The preparation protocols of these nucleoside scintigraphic probes are also described.

The outcome of heart transplantation in hepatitis C-positive recipients.

BACKGROUND: Clinical outcomes of heart transplantation (HTx) among recipients with chronic hepatitis C virus (HCV) infection are poorly understood especially in Asia. Therefore, this study evaluated these clinical outcomes. METHODS: Using retrospective chart review we collected data on 385 patients including 20 HCV-positive recipients at the time of transplantation. We obtained information on demographics features, serial transaminases, graft function, patient survival as well as the incidences of acute hepatitis and transplant coronary artery disease. RESULTS: Between 1987 and 2010, the 20 HCV-positive patients had a median age at transplantation of 52 years (range, 30-63). Seventeen were men and three women. All the patients were classified as Child-Pugh class A; two had cirrhosis prior to HTx. Over a mean follow-up of 63 months (range, 2 days to 187 months), there were 11 deaths, including two hospital mortalities and nine subsequent deaths. Only one mortality (5%) was related to Child-Pugh class C cirrhosis, despite liver transplantation. Among the other 19 deceased or surviving recipients, there was no evidence of hepatic dysfunction or hepatocellular carcinoma. Transplant coronary artery disease was detected in six patients (30%). There was no significant difference in Kaplan-Meier actuarial survival between the HCV-positive and HCV-negative recipients (P = .59). CONCLUSIONS: There was no significant difference in patient survival or graft function between HCV-positive and HCV-negative HTx recipients. Additionally, HCV-positive recipients were not at an increased risk of hepatic failure or accelerated transplant coronary artery disease.

SU-E-T-464: Impact of the Treatment Margin on Tumor Control and Normal Tissue Complication for Prostate Treatment.

PURPOSE: To investigate the consequence of treatment margin reduction on normal tissue complication probability (NTCP) and tumor control probability (TCP) of prostate external beam treatment. METHODS: Intensity modulated rotational radiotherapy plans were generated for 10 prostate patients with 6 different posterior margin sizes from 5mm to 0. The prescription dose is 80Gy for 40 treatment fractions. The dose distributions were recalculated with consideration of the intrafractional motion and the localization error. The statistical uncertainties of the intrafractional motion and the localization error were derived based on the motion tracking data recorded by the Calypso 4D localization system for a large patient population. The TCP and NTCP were calculated based on the dose volume histograms (DVH) of prostate and rectum for plans with different margins using an equivalent uniform dose (EUD) based biological model. The 50% tumor control dose (TCD50) of 60Gy for prostate and the median toxic dose (TD50) of 55Gy for rectum were used in the calculation. RESULTS: The minimum dose of the prostate and the mean dose of the rectum dropped with the decrease of the treatment margin. When the posterior treatment margin was reduced from 5mm to zero, the EUD of prostate decreased from 83Gy (±0.5Gy) to 81Gy (±0.5Gy) and the TCP dropped from 93.2% (±0.1%) to 91.7% (±0.1%), the EUD of the rectum decreased more significantly from 48.9Gy (±0.4Gy) to 32.5Gy (±0.5Gy) and the NTCP dropped from 13.3% (±1.5%) to 0.03% (± 0.01%). CONCLUSIONS: The treatment margin size affects the dose to the target and the nearby critical structure. More significant impact on NTCP has been observed than on TCP. This gives us some room to consider the quality of the patient's after-treatment life. A wise choice of treatment margin can be made based on physician's opinion and patient's preference on the tumor control and the quality of life.

Impact of neck dissection in early tongue and buccal cancer without neck extension.

PROBLEM: The role of elective neck dissection in early stage tongue and buccal squamous cell carcinoma with negative neck lymph nodes is still controversial. METHODS: We retrospectively reviewed patients with T1-2N0M0 buccal and tongue cancer who underwent primary tumour excision with or without elective neck dissection between January 1997 and December 2006. RESULTS: Elective neck dissection specifically improved disease-free survival of T2N0M0 buccal cancer and overall survival of T2N0M0 tongue cancer. CONCLUSION: Elective neck dissection seems to improve the disease-free survival rate of T2N0M0 buccal cancer and the overall survival rate of T2N0M0 tongue cancer but has no beneficial effect on the survival rate of T1N0M0 buccal and tongue cancer.

Correlation between the MR T2 value at 4.7 T and relative water content in articular cartilage in experimental osteoarthritis induced by ACL transection.

OBJECTIVE: Both animal and human studies using magnetic resonance imaging (MRI) show that cartilage degeneration increases the T2 value. However, it is unclear whether the T2 value correlates linearly with water content in cartilage with osteoarthritis. The purpose of this study was to investigate the relationship between the T2 value and water content using an animal model of cartilage injury measured at 4.7 T. DESIGN: Thirty Sprague Dawley rats were randomly separated into three groups (n=10 for each group). Group 1 rats were not operated on (control). Group 2 rats received a sham operation, and group 3 rats received an anterior cruciate ligament (ACL) transection. Six rats of each group were randomly assigned to T2 measurement and later subjected to ex vivo analysis of the relative water content of the knee cartilage. The other four rats in each group were killed, and the severity of cartilage degeneration was examined histologically. The knees of the six rats in the ACL transection group were imaged sequentially 4 and 13 weeks after ACL transection, and the relative water content was measured at 13 weeks. RESULTS: The cartilage T2 value was significantly higher 4 and 13 weeks after ACL transection in the operated knees than in the knees of the control and sham groups. The cartilage T2 value was significantly higher at 13 weeks than at 4 weeks in the operated knees. The T2 value was strongly positively correlated with the relative water content (R=0.885, P<0.0001). CONCLUSION: The trend of changes in the T2 values is consistent with an increase in the relative water content in our cartilage degeneration model. This model has potential use for the clinical evaluation of osteoarthritis.