Loss of Proximal Tubular Sirtuin 6 Aggravates Unilateral Ureteral Obstruction-Induced Tubulointerstitial Inflammation and Fibrosis by Regulation of ß-Catenin Acetylation.

Renal fibrosis is a significant pathologic change associated with progressive kidney disease. Sirt6 is an NAD+-dependent deacetylase and mono-ADP ribosyltransferase known to play diverse roles in the processes attendant to aging, metabolism, and carcinogenesis. However, the role of proximal tubule-specific Sirt6 in renal fibrosis remains elusive. This study investigates the effect of proximal tubule-specific Sirt6 knockdown on unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial inflammation and fibrosis. Renal fibrosis in wild type and PT-Sirt6KO (Sirt6flox/flox; Ggt1-Cre+) mice was induced by UUO surgery. After seven days, histologic examination and Western blot analysis were performed to examine extracellular matrix (ECM) protein expression. We evaluated inflammatory cytokine and cell adhesion molecule expression after ureteral obstruction. The therapeutic effect of Sirt6 activator MDL-800 on UUO-induced tubulointerstitial inflammation and fibrosis was assessed. The loss of Sirt6 in the proximal tubules aggravated UUO-induced tubular injury, ECM deposition, F4/80 positive macrophage infiltration, and proinflammatory cytokine and chemokine expression. Sirt6 activator MDL-800 mitigated UUO-induced renal tubulointerstitial inflammation and fibrosis. In an in vitro experiment, MDL-800 decreases the transforming growth factor (TGF)-ß1-induced activation of myofibroblast and ECM production by regulating Sirt6-dependent ß-catenin acetylation and the TGF-ß1/Smad signaling pathway. In conclusion, proximal tubule Sirt6 may play an essential role in UUO-induced tubulointerstitial inflammation and fibrosis by regulating Sirt6-dependent ß-catenin acetylation and ECM protein promoter transcription.

Hypofractionated Radiotherapy for Early-Stage Breast Cancer: A Propensity Score Matched Analysis.

BACKGROUND: In patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost. METHODS: We retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR). DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test. RESULTS: Total 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated. The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%). CONCLUSION: Hypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Evaluation of monoxide film-based dosimeters for surface dose detection in electron therapy.

Generally, electron therapy is applied to tumors on or close to the skin surface. However, this causes a variety of skin-related side effects. To alleviate the risk of these side effects, clinical treatment uses skin dosimeters to verify the therapeutic dose. However, dosimeters suffer from poor accuracy, because their attachment sites are approximated with the help of naked eyes. Therefore, a dosimeter based on a flexible material that can adjust to the contours of the human body is required. In this study, the reproducibility, linearity, dose-rate dependence, and percentage depth ionization (PDI) of PbO and HgO film-based dosimeters are evaluated to explore their potential as large-scale flexible dosimeters. The results demonstrate that both dosimeters deliver impressive reproducibility (within 1.5%) and linearity (≥ 0.9990). The relative standard deviations of the dose-rate dependence of the PbO and HgO dosimeters were 0.94% and 1.16% at 6 MeV, respectively, and 1.08% and 1.25% at 9 MeV, respectively, with the PbO dosimeter outperforming the 1.1% of existing diodes. The PDI analysis of the PbO and HgO dosimeters returned values of 0.014 cm (-0.074 cm) and 0.051 cm (-0.016 cm), respectively at 6 MeV (9 MeV) compared to the thimble chamber and R50. Therefore, the maximum error of each dosimeter is within the allowable range of 0.1 cm. In short, the analysis reveals that the PbO dosimeter delivers a superior performance relative to its HgO counterpart and has strong potential for use as a surface dosimeter. Thus, flexible monoxide materials have the necessary qualities to be used for dosimeters that meet the requisite quality assurance standards and can satisfy a variety of radiation-related applications as flexible functional materials.

A dummy-run evaluation of postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trials for cervical cancer.

The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous.

The tacrolimus metabolism affect post-transplant outcome mediating acute rejection and delayed graft function: analysis from Korean Organ Transplantation Registry data.

Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies. The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D). The patients were grouped into fast, intermediate, or slow metabolizers by the C0 /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m2 higher adjusted estimated glomerular filtration rate (eGFR) at 6 months [95% confidence interval (C.I.) 1.2-4.3, P = 0.001], less acute rejection (AR) within 6 months [Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, P = 0.016], and less interstitial fibrosis and tubular atrophy [OR 0.606, 95% C.I. 0.390-0.940, P = 0.025]. Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR [natural indirect effect (NIE) -0.434, 95% C.I. -0.856 to -0.012, P = 0.044) and delayed graft function (DGF; NIE -0.119, 95% C.I. -0.231 to -0.007, P = 0.038). Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis.

Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-ß1/Smad signaling pathway.

Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κBTGF-ß1/Smad Signaling Pathway.

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3(SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrialbiogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as apharmaceutical SIRT3 activator, has been observed to have a protective effect against pressureoverload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigatedwhether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction(UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation ofmitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubularinjury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblastactivation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKLtreatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusionthrough SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might havebeneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation ofmitochondrial dynamics and the NF-κB/TGF-ß1/Smad signaling pathway.

Maximum standardized uptake value at pre-treatment PET in estimating lung cancer progression after stereotactic body radiotherapy.

PURPOSE: This study aimed to identify the feasibility of the maximum standardized uptake value (SUVmax) on baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) as a predictive factor for prognosis in early stage primary lung cancer treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Twenty-seven T1-3N0M0 primary lung cancer patients treated with curative SBRT between 2010 and 2018 were retrospectively evaluated. Four patients (14.8%) treated with SBRT to address residual tumor after wedge resection and one patient (3.7%) with local recurrence after resection were included. The SUVmax at baseline PET/CT was assessed to determine its relationship with prognosis after SBRT. Patients were divided into two groups based on maximum SUVmax on pre-treatment FDG PET/CT, estimated by receiver operating characteristic curve. RESULTS: The median follow-up period was 17.7 months (range, 2.3 to 60.0 months). The actuarial 2-year local control, progressionfree survival (PFS), and overall survival were 80.4%, 66.0%, and 78.2%, respectively. With regard to failure patterns, 5 patients exhibited local failure (in-field failure, 18.5%), 1 (3.7%) experienced regional nodal relapse, and other 2 (7.4%) developed distant failure. SUVmax was significantly correlated with progression (p = 0.08, optimal cut-off point SUVmax > 5.1). PFS was significantly influenced by pretreatment SUVmax (SUVmax > 5.1 vs. SUVmax ≤ 5.1; p = 0.012) and T stage (T1 vs. T2-3; p = 0.012). CONCLUSION: SUVmax at pre-treatment FDG PET/CT demonstrated a predictive value for PFS after SBRT for lung cancer.

Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy.

PURPOSE: Recent studies revealed that metabolic stress influences the outcomes of breast cancer treatment. We sought to evaluate the prognostic effect of type 2 diabetes and find the molecular mechanism of relapses in postoperative HER-2+ breast cancer patients treated with HER-2 targeted therapy. MATERIALS AND METHODS: We evaluated 190 HER-2+ breast cancer patients (pT1-4N0-2M0) who were treated with surgical resection and trastuzumab (HER-2 targeted therapy) between 2006 and 2015. Survival outcomes and failure patterns were compared between such patients with (n = 12) and without (n = 178) type 2 diabetes. RESULTS: The median follow-up period was 42.4 months (range 12.0-124.7 months). Twenty-one patients (11.1%) showed relapse (including nine patients with locoregional failure), and three patients (1.6%) died as a result of cancer relapse. One-third of the patients with diabetes experienced relapse (4/12, 33.3%). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 90.7% and 98.6%, respectively. Diabetic patients showed shorter DFS compared with non-diabetic patients (p = 0.006, 74.1% vs. 91.9%). OS was also shorter in diabetic patients compared with non-diabetic patients (p = 0.017, 91.7% vs. 99.1%). Of our interest, the levels of HER-3 and its ligand neuregulin-1 were significantly increased in the tumor specimen in HER-2+ breast cancer patients suffering with type 2 diabetes than that in the euglycemic control group. CONCLUSIONS: Type 2 diabetes was associated with detrimental effects on survival in postoperative HER-2+ breast cancer patients who were treated with trastuzumab. The poor prognostic effect of diabetes in HER-2+ breast cancer patients could be associated with the high levels of HER-3 and neuregulin 1, thus it should be considered and evaluated more.

Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular apoptosis and inflammation.

Cisplatin­based chemotherapy is commonly used in the treatment of solid tumors; however, this agent is limited by its adverse effects on normal tissues, including the kidneys, ears and peripheral nerves. Mechanisms of cisplatin nephrotoxicity are proposed to involve oxidative stress, inflammation, cellular apoptosis and cell cycle regulation. Sirtuin 3 (Sirt3) is a member of the sirtuin family of NAD+­dependent enzymes with homology to Saccharomyces cerevisiae gene silent information regulator 2. Sirt3 is located in mitochondria and is involved in mitochondrial energy metabolism and function; however, the role of Sirt3 in cisplatin nephrotoxicity remains unclear. In the present study, whether Sirt3 has anti­inflammatory and anti­apoptotic effects on cisplatin­induced nephrotoxicity was investigated in mice. Sirt3 knockout mice (Sirt3(­/­)) and corresponding wild type mice were employed in the present study. Cisplatin nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg). After 3 days following cisplatin treatment, blood and kidney tissues were harvested. Renal function and histology were evaluated. Tubular apoptosis, cell adhesion molecule expression, and inflammatory cells were evaluated by immunohistochemistry and western blot analysis. Following the induction of cisplatin nephrotoxicity, renal function was significantly aggravated in Sirt3 knockout (KO) mice. Tubular injury and inflammatory cell infiltration were significantly increased in Sirt3KO mice compared with wild type mice. Terminal deoxynucleotidyl transferase­mediated dUTP nick­end label­positive tubular cells and renal monocyte chemoattractant protein­1 expression levels were increased in Sirt3KO mice compared with in wild type mice. In summary, the absence of Sirt3 aggravated in renal injury by increasing renal inflammation and tubular apoptosis. The results of the present study suggested that Sirt3 may have an important role in cisplatin­induced nephrotoxicity.

Opsoclonus-myoclonus syndrome following long-term use of cyclosporine.

BACKGROUND: Cyclosporine A (CsA) is a widely used immunosuppressive agent that may provoke unexpected neurologic complications. The mechanism is unclear and variable intervals have been reported between CsA administration and onset of the related side effects. Here, we describe a case of delayed-onset CsA neurotoxicity presenting as opsoclonus-myoclonus syndrome (OMS). CASE DETAILS: A 37-year-old woman with a two-week period of opsoclonus and upper extremity myoclonus was admitted to our hospital. The patient had been taking CsA for 17 years after receiving a kidney transplant. Further evaluation did not reveal any other abnormalities. Seven days after switching from CsA to tacrolimus, in the absence of additional immune-modulating therapy, her neurologic symptoms improved considerably. CONCLUSION: This is the case of delayed, long-term complications of CsA presenting as OMS. Symptoms resolved by substituting CsA with another immunomodulating drug. The etiology of the neurologic complications may involve paradoxically-enhanced delayed-type hypersensitivity.

Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice.

Renal tubulointerstitial fibrosis is characterized by sustained inflammation and excessive extracellular matrix (ECM) accumulation, leading to chronic kidney disease. Valproic acid (VPA) has anticancer activity through regulation of cell differentiation and apoptosis via inhibition of histone deacetylase (HDAC) activity and is considered a class I HDAC inhibitor. In this study, the effect of VPA on unilateral ureteral obstruction (UUO)­induced renal fibrosis by modulation of renal inflammation and ECM gene transcription was investigated. VPA treatment increased histone H3 acetylation in both sham­ and UUO­operated kidneys and decreased the UUO­induced increase in tubular injury and ECM deposition in mice. VPA also decreased myofibroblast activation and proliferation in UUO kidneys and NRK­49F cells. Finally, it was demonstrated that the anti­fibrotic effect of VPA was associated with regulation of ECM protein promoter enrichment at an acetylated histone H3 site. In conclusion, the findings indicate that VPA may have a beneficial effect on UUO­induced renal fibrosis via regulation of myofibroblast activation, proliferation, and ECM protein production by chromatin remodeling and ECM protein promoter transcription.

Image similarity evaluation of the bulk-density-assigned synthetic CT derived from MRI of intracranial regions for radiation treatment.

OBJECTIVE: Various methods for radiation-dose calculation have been investigated over previous decades, focusing on the use of magnetic resonance imaging (MRI) only. The bulk-density-assignment method based on manual segmentation has exhibited promising results compared to dose-calculation with computed tomography (CT). However, this method cannot be easily implemented in clinical practice due to its time-consuming nature. Therefore, we investigated an automatic anatomy segmentation method with the intention of providing the proper methodology to evaluate synthetic CT images for a radiation-dose calculation based on MR images. METHODS: CT images of 20 brain cancer patients were selected, and their MR images including T1-weighted, T2-weighted, and PETRA were retrospectively collected. Eight anatomies of the patients, such as the body, air, eyeball, lens, cavity, ventricle, brainstem, and bone, were segmented for bulk-density-assigned CT image (BCT) generation. In addition, water-equivalent CT images (WCT) with only two anatomies-body and air-were generated for a comparison with BCT. Histogram comparison and gamma analysis were performed by comparison with the original CT images, after the evaluation of automatic segmentation performance with the dice similarity coefficient (DSC), false negative dice (FND) coefficient, and false positive dice (FPD) coefficient. RESULTS: The highest DSC value was 99.34 for air segmentation, and the lowest DSC value was 73.50 for bone segmentation. For lens segmentation, relatively high FND and FPD values were measured. The cavity and bone were measured as over-segmented anatomies having higher FPD values than FND. The measured histogram comparison results of BCT were better than those of WCT in all cases. In gamma analysis, the averaged improvement of BCT compared to WCT was measured. All the measured results of BCT were better than those of WCT. Therefore, the results of this study show that the introduced methods, such as histogram comparison and gamma analysis, are valid for the evaluation of the synthetic CT generation from MR images. CONCLUSIONS: The image similarity results showed that BCT has superior results compared to WCT for all measurements performed in this study. Consequently, more accurate radiation treatment for the intracranial regions can be expected when the proper image similarity evaluation introduced in this study is performed.

Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy.

PURPOSE: This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). RESULTS: The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. CONCLUSION: Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

Correction: Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy.

[This corrects the article on p. 48 in vol. 35.].

Being Overweight or Obese Increases the Risk of Progression in Triple-Negative Breast Cancer after Surgical Resection.

This study aimed to evaluate the association between body mass index (BMI) and progression in triple-negative breast cancer (TNBC). We retrospectively reviewed the medical records of 50 patients with TNBC who underwent breast-conserving surgery or mastectomy between 2007 and 2014. All patients were classified according to BMI (median 23.5 kg/m(2), range 17.2-31.6 kg/m(2)): 31 patients (62%) were classified as being overweight or obese (BMI ≥ 23 kg/m(2)) and 19 patients (38%) were classified as having a normal body weight (BMI < 23 kg/m(2)). The median follow-up for patients was 31.1 months (range, 6.7-101.9 months). Progression occurred in 7 patients (14%), including 5 ipsilateral breast tumor recurrences, 2 regional lymph node metastases, and 5 distant metastases. Progression was significantly correlated with overweight or obese patients (P = 0.035), while none of the normal weight patients showed progression. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 85.0% and 87.7%, respectively. DFS was significantly reduced in overweight or obese patients compared to that in normal weight patients (P = 0.035). However, OS was not significantly compromised by being overweight or obese (P = 0.134). In conclusion, being overweight or obese negatively affects DFS in TNBC patients.

Setup uncertainties for inter-fractional head and neck cancer in radiotherapy.

PURPOSE: The aim of this study is to determine the inter-fractional motion of cervical spine in radiotherapy (RT). MATERIALS AND METHODS: Eleven localized head and neck cancer patients who were treated from April 2014 to September 2015 were evaluated. Every patient underwent 3 times of computed tomography (CT) simulation with equivalent setting. Left-right (LR, x) and antero-posterior (AP, z) directional shift of cervical spine were evaluated using 33 number of CT image. In regard to random error, geometric changes were evaluated by 22 data set (compared the first obtained CT to second or third CT) by one-sample T test. Systemic error was evaluated by each patients' data set (11 pairs) by paired T test. RESULTS: The mean random error of LR and AP translational shift of cervical spine were -0.39 ± 3.24 mm and -0.57 ± 0.99 mm respectively. The mean random error of translational change of AP direction showed statistical significance (p = 0.014). The mean random error of x and z rotational shift were -0.07 ± 0.29° and -0.05 ± 0.35°, respectively. The mean systemic error of translational shift of LR and AP direction were -0.64 ± 2.57 mm and -0.33 ± 1.22 mm, respectively. The mean systemic error of rotational shift of x and z were 0.01 ± 0.18° and -0.27 ± 0.33°, respectively. The mean systemic error of rotational changes of z direction showed statistical difference (p = 0.022). CONCLUSIONS: We have to be aware of the inter-fractional motion of cervical spine in head and neck RT and give enough margins in RT planning.

Association between obesity and local control of advanced rectal cancer after combined surgery and radiotherapy.

PURPOSE: The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2-3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m(2)) in local control was evaluated. RESULTS: The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m(2) as a cutoff value. CONCLUSION: Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted.

Efficacy of Dose-Escalated Radiotherapy for Recurrent Colorectal Cancer.

PURPOSE: This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. METHODS: We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45-75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. RESULTS: The median follow-up period was 24.9 months (range, 4.5-66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). CONCLUSION: Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression.