Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF-CRT) for locally advanced squamous cell carcinoma of the external auditory canal.

PURPOSE: Chemoradiotherapy with docetaxel (DOC), cisplatin (CDDP), and 5-FU (TPF-CRT) for locally advanced external auditory canal cancer (EACC) has favorable oncological and functional outcomes. To establish TPF-CRT as a standard of care for advanced EACC, we conducted this study to determine the maximum tolerated (MTD) and recommended dose (RD) of DOC in TPF-CRT for locally advanced EACC. METHODS: To determine the recommended (RD) and maximum tolerated dose (MTD) of DOC in TPF-CRT for EACC, a phase I trial was conducted using the standard "3 + 3" design for maximum dose finding. DOC was administered twice every 4 weeks, CDDP at 70 mg/m2 and 5-FU at 700 mg/m2; patients were also receiving radiotherapy (66 Gy). Eight patients with T3 or T4 EACC were prospectively enrolled. RESULTS: Two patients treated with DOC, 50 mg/m2, and one out of six patients treated with DOC, 40 mg/m2, had dose-limiting toxicities. Prolonged febrile neutropenia was observed in three patients. Grade 3 non-hematological toxicities were observed in only three patients. At study completion, six patients survived, five of whom were disease free. CONCLUSION: The RD and MTD of DOC in TPF-CRT for locally advanced EACC are 40 mg/m2 when doses of CDDP and 5-FU are 70 mg/m2 and 700 mg/m2, respectively.

[Dose Verification for Respiratory-gated VMAT-SBRT Using Real-time Tumor Tracking System].

Recently, the introduction of various novel technologies in clinical settings has improved the accuracy of radiation therapy. Stereotactic body radiation therapy (SBRT) involves the delivery of an accurate radiation dose to the tumor with a minimal impact on normal tissues using various measures to address changes in the tumor position due to respiratory displacement. The SyncTraX FX4 real-time tumor tracking system (Shimadzu Corporation) introduced in our hospital tracks the actual tumor location by radioscopically monitoring a metallic marker that is placed in the vicinity of the tumor. However, there have been no reports yet on respiratory-gated volumetric modulated arc therapy (VMAT)-SBRT using a real-time tumor tracking system. This study aimed to develop an irradiation procedure for respiratory-gated VMAT-SBRT using a real-time tumor tracking system and to evaluate radiation doses therein. In this study, we found that absolute doses with respiratory gating did not deviate by more than ±1.0% from those without respiratory gating. In addition, the pass rate in gamma analysis using GAFCHROMIC EBT3 was ³95% with the pass criteria in dose difference, distance to agreement, and threshold being 2%, 2 mm, and 10%, respectively. Furthermore, a trajectory log file analysis did not reveal any significant error causes. Thus, these data indicate that respiratory-gated VMAT-SBRT can be applied clinically.

Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer : Evaluation of indications and predictors of local control.

AIM: To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases (BMs) from lung cancer, and to explore prognostic factors associated with local control (LC) and indication. PATIENTS AND METHODS: We evaluated patients who were treated with linac-based HSRT for BMs from lung cancer. Lesions treated with stereotactic radiosurgery (SRS) in the same patients during the same periods were analysed and compared with HSRT in terms of LC or toxicity. There were 53 patients with 214 lesions selected for this analysis (HSRT: 76 lesions, SRS: 138 lesions). For HSRT, the median prescribed dose was 35 Gy in 5 fractions. RESULTS: The 1­year LC rate was 83.6 % in HSRT; on multivariate analysis, a planning target volume (PTV) of <4 cm(3), biologically effective dose (BED10) of ≥51 Gy, and adenocarcinoma were significantly associated with better LC. Moreover, in PTVs ≥ 4 cm(3), there was a significant difference in LC between BED10 < 51 Gy and ≥ 51 Gy (p = 0.024). On the other hand, in PTVs < 4 cm(3), both HSRT and SRS had good LC with no significant difference (p = 0.195). Radiation necrosis emerged in 5 of 76 lesions (6.6 %) treated with HSRT and 21 of 138 (15.2 %) lesions treated with SRS (p = 0.064). CONCLUSION: Linac-based HSRT was safe and effective for BMs from lung cancer, and hence might be particularly useful in or near an eloquent area. PTV, BED10, and pathological type were significant prognostic factors. Furthermore, in BMs ≥ 4 cm(3), a dose of BED ≥ 51 Gy should be considered.

Instructive percutaneous coronary intervention to avoid the risk of side branch occlusion at a lesion with a lotus root appearance: a case report.

BACKGROUND: A lotus root appearance is a rare entity, and there is little opportunity to perform coronary intervention for this kind of lesion. Because of its peculiar anatomical characteristics, one of the problems regarding percutaneous coronary intervention (PCI) for these lesions is related to the involvement of branch vessels. CASE PRESENTATION: We encountered a case of PCI for a stenotic lesion with a lotus root appearance in the mid-portion of the right coronary artery (RCA). To avoid the risk of right ventricular (RV) branch occlusion due to stent deployment in the main RCA, we re-crossed the third guidewire into the main RCA via the nearest point to the RV branch ostium through the communicating vascular lumen. Thereafter, we deployed a drug-eluting stent in the main RCA crossing over the RV branch, and the ostium of the RV branch remained intact, as we expected. CONCLUSIONS: This case is the first report in the world describing the details of how to maintain the patency of the side branch bifurcating from a lesion with a lotus root appearance under optical coherence tomography guidance.

Practical Usefulness of Dual Lumen Catheter-Facilitated Reverse Wire Technique for Markedly Angulated Bifurcated Lesions.

OBJECTIVES: This study aimed to investigate the practical usefulness of dual lumen catheter-facilitated reverse wire technique. BACKGROUND: We sometimes encounter difficulty in introducing a guidewire to the highly angulated side branch. In those cases, the reverse wire technique is considered as a last resort to overcome the situation. METHODS: Between January 2013 and June 2015, we performed the reverse wire technique for guidewire crossing into an extremely angulated side branch in consecutive seven cases with true bifurcated lesions. We retrospectively evaluated patients' backgrounds, lesion characteristics, and details of the percutaneous coronary intervention (PCI) procedures. RESULTS: Three interventional cardiologists with various levels of experience in coronary intervention performed this technique. A polymer-jacket hydrophilic-coated guidewire was used for the reverse wire system excluding in one case, and we adopted a sharp curve for the tip shape in all cases. After crossing the reverse wire into a highly angulated side branch, we usually deliver a flexible micro catheter over the guidewire for the purpose of guidewire exchange. We deployed a stent in the side branch in three cases. We successfully performed all PCI procedures without any complications and no major adverse cardiac event was observed during hospitalization. CONCLUSIONS: We could safely and effectively perform the reverse wire technique for guidewire crossing into a markedly angulated side branch. We recommend a polymer-jacket hydrophilic-coated guidewire with a sharp curve in the tip shape for this technique. All interventional cardiologists should acquire knowledge and skills regarding this guidewire manipulation technique.

Treatment outcomes of the patients with early glottic cancer treated with initial radiotherapy and salvaged by conservative surgery.

OBJECTIVE: This retrospective study analyzed the oncological and treatment outcomes of the patients with T1-T2N0 glottic cancer, who were treated with radiotherapy as initial treatment and salvaged by conservative surgery for radiation failure. METHODS: Between May 1999 and December 2010, 115 patients with glottic laryngeal cancer were treated at Kobe University Hospital. At presentation, 54 patients had stage T1a disease, 26 had stage T1b disease and 35 had stage T2 disease. Seventy-nine patients were treated with conventional radiotherapy and 36 patients were treated with hyperfractionated radiotherapy as initial treatment. RESULTS: Median duration of follow-up was 61 months. Five-year local control rates of radiotherapy were 92% in T1a, 83% in T1b and 86% in T2. Of 12 patients who developed local recurrence, larynx was successfully preserved in 3 patients by laryngomicrosurgery, 7 patients by vertical partial laryngectomy and one patient by subtotal laryngectomy. Ultimate 5-year laryngeal preservation rate and local control rate of all cases were 99 and 100%, respectively. CONCLUSIONS: Present results suggest that initial treatment with radiotherapy salvaged by organ preservation surgery is an effective strategy for laryngeal preservation in the treatment of T1-T2N0 glottic laryngeal cancer.

Primary CNS lymphoma treated with radiotherapy in Japan: a survey of patients treated in 2005-2009 and a comparison with those treated in 1985-2004.

BACKGROUND: The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). METHODS: Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995-2004 and those on 466 patients treated during the period 1985-1994. RESULTS: In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005-2009 period compared to the 1985-2004 period (63 vs. 58-59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005-2009 period compared with the 1995-2004 period (World Health Organization PS 0-2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995-2004 period, significant changes in the 2005-2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985-1994, 1995-2004, and 2005-2009 periods, respectively, but relapse-free survival did not improve between the 1995-2004 and 2005-2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. CONCLUSIONS: Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.

Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.

The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

Oncological Outcomes of Concurrent Chemoradiotherapy and Surgical Treatment for Patients With T3 Hypopharyngeal Cancer: A Single-Center Retrospective Analysis.

Background Since the larynx and pharynx are vital for respiration, swallowing, and speech, chemoradiotherapy (CRT) has been widely applied for T3 hypopharyngeal cancer (HPC) as an organ-preserving treatment. However, CRT can lead to severe late adverse events such as dysphagia and aspiration pneumonia, especially in patients who have difficulty swallowing and/or aspiration at the time of initial diagnosis. Patients and methods Between 2012 and 2020, 86 patients with T3 HPC treated with curative intent at Kobe University Hospital were included in this study. The average age was 69 years old, ranging from 43 to 89. Diseases were classified as Stage III in 29 patients, Stage IVA in 52 patients, and Stage IVB in five patients. Thirty-five (41%) patients were treated by CRT, and 51 (59%) patients were treated by surgery. Patients were followed up for at least two years, and the follow-up period ranged from four to 128 months (median: 45 months). Results Three-year progression-free survival (PFS) rates of patients treated by CRT and patients treated by surgery were 56.2% and 60.3%, respectively. Three-year disease-specific survival (DSS) rates of patients treated by CRT and surgically treated patients were 79.0% vs. 70.8%, respectively. Three-year overall survival (OS) rates of patients treated by CRT and surgically treated patients were 64.5% and 69.0%, respectively. Of note, a significant difference was observed between three-year DSS and three-year PFS (79.0% vs. 56.2%, p = 0.0014) in the patients treated by CRT but not in the patients treated by surgery. Conclusions No significant differences were observed between the PFS, DSS, and OS rates of patients treated by CRT and those of surgically treated patients. Locoregional recurrences after CRT were significantly successfully salvaged by surgical intervention. These results suggest that CRT can be applied as an alternative to surgery without reducing survival, especially for patients without severe clinical symptoms. Meticulous follow-up is mandatory for early detection of recurrence to salvage by surgery and for the management of late adverse events.

Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1-T2 Squamous Cell Carcinoma of the Glottic Larynx.

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1-T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.

[Evaluation of absorbed dose from kilovoltage cone-beam computed tomography by radiotherapy planning system: influence on the radiation therapy for prostate cancer].

Image-guided radiation therapy (IGRT) is increasingly being used in modern radiation therapy, and it is now possible to verify a patient's position using kilo-voltage cone-beam computed tomography (kV-CBCT). However, if kV-CBCT is used frequently, the dose absorbed by the body cannot be disregarded. A number of studies have been made on the absorbed dose of kV-CBCT, in which absorbed dose measurements were made using a computed tomography dose index (CTDI) or a thermoluminescent dosimeter (TLD). Other methods include comparison of the absorbed dose between a kV-CBCT and other modalities. These techniques are now in common use. However, dose distribution within the patient varies with the patient's size, posture and the part of the body to which radiation therapy is applied. The chief purpose of this study was to evaluate the dose distribution of kV-CBCT by employing a radiotherapy planning system (RTPS); a secondary aim was to examine the influence of a dose of kV-CBCT radiation when used to treat prostate cancer. The beam data of an on-board imager (OBI) was registered in the RTPS, after which modeling was performed. The radiation dosimetry was arranged by the dosimeter in an elliptical phantom. Rotational radiation treatment was used to obtain the dose distribution of the kV-CBCT within the patient, and the patient dose was evaluated based on the simulation of the dose distribution. In radiation therapy for prostate cancer, if kV-CBCT was applied daily, the dose increment within the planning target volume (PTV) and the organ in question was about 1 Gy.

Prognostic Value of Radiomics Analysis of Skeletal Muscle After Radical Irradiation of Esophageal Cancer.

BACKGROUND/AIM: Sarcopenia is an independent survival predictor in several tumor types. Computed tomography (CT) is the standard measurement for body composition assessment. Radiomics analysis of CT images allows for the precise evaluation of skeletal muscles. This study aimed to construct a prognostic survival model for patients with esophageal cancer who underwent radical irradiation using skeletal muscle radiomics. PATIENTS AND METHODS: We retrospectively identified patients with esophageal cancer who underwent radical irradiation at our institution between April 2008 and December 2017. Skeletal muscle radiomics were extracted from an axial pretreatment CT at the third lumbar vertebral level. The prediction model was constructed using machine learning coupled with the least absolute shrinkage and selection operator (LASSO). The predictive nomogram model comprised clinical factors with radiomic features. Three prediction models were created: clinical, radiomics, and combined. RESULTS: Ninety-eight patients with 98 esophageal cancers were enrolled in this study. The median observation period was 57.5 months (range=1-98 months). Thirty-five radiomics features were selected by LASSO analysis, and a prediction model was constructed using training and validation data. The average of the accuracy, specificity, sensitivity, and area under the concentration-time curve for predicting survival in esophageal cancer in the combined model were 75%, 92%, and 0.86, respectively. The C-indices of the clinical, radiomics, and combined models were 0.76, 0.80, and 0.88, respectively. CONCLUSION: A prediction model with skeletal muscle radiomics and clinical data might help determine survival outcomes in patients with esophageal cancer treated with radical radiotherapy.

Oncological outcomes of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced squamous cell carcinoma of the external auditory canal: A single-center study.

BACKGROUND: Squamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. However, a standard treatment has not yet been established. We retrospectively evaluated the efficacy, adverse events, and feasibility of TPF-CCRT (concomitant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced EACSCC. METHODS: Thirty-five consecutive patients with advanced EACSCC (T3, T4) initially treated with TPF-CCRT at Kobe University Hospital were included. T4 diseases with invasion of the brain, internal carotid artery, or internal jugular vein were classified as T4b, and those without these features were classified as T4a. RESULTS: Five-year overall survival rates for T3 and T4 were 100% and 64.2%, respectively. A significant difference was observed between T4a and T4b (82.4% vs. 30%, p = 0.007). Five-year progression-free survival rates of T3, T4a, and T4b were 100%, 68%, and 20% (p = 0.022), respectively. CONCLUSIONS: TPF-CCRT should be considered as a plausible treatment option for advanced EACSCC.

Maternal high-fat diet promotes calcified atherosclerotic plaque formation in adult offspring by enhancing transformation of VSMCs to osteochondrocytic-like phenotype.

Aim: Maternal high-fat diet (HFD) is associated with the development of cardiovascular disease (CVD) in adult offspring. Atherosclerotic vascular calcification is well documented in patients with CVD. We examined the effect of maternal HFD on calcified plaque formation. Methods and results: Seven-week-old female apo-E-/- mice (C57BL6/J) were nourished either an HFD or a normal diet (ND) a week before mating, and during gestation and lactation. Offspring of both the groups were fed a high-cholesterol diet (HCD) from 8 weeks of age. Osteogenic activity of the thoracic aorta, assessed using an ex vivo imaging system, was significantly increased after 3 months of HCD in male offspring of HFD-fed dams (O-HFD) as compared with those of ND-fed dams (O-ND). Alizarin-red-positive area in the aortic root was significantly increased after 6 months of HCD in male O-HFD as compared to that of O-ND. Plaque size and Oil Red O-positive staining were comparable between the two groups. Primary cultured vascular smooth muscle cells (VSMCs) of the thoracic aorta were treated with phosphate and interleukinL-1ß (IL-1ß) to transform them into an osteochondrocytic-like phenotype. Intracellular calcium content and alkaline phosphatase activity were markedly higher in the VSMCs of O-HFD than in O-ND. IL-1ß concentration in the supernatant of bone marrow-derived macrophages was markedly higher in O-HFD than in O-ND. Conclusion: Our findings indicate that maternal HFD accelerates the expansion of atherogenic calcification independent of plaque progression. In vitro phosphate- and IL-1ß-induced osteochondrocytic transformation of VSMCs was augmented in O-HFD. Inhibition of VSMCs, skewing toward osteochondrocytic-like cells, might be a potential therapeutic strategy for preventing maternal HFD-associated CVD development.

Repeated Social Defeat Enhances CaCl2-Induced Abdominal Aortic Aneurysm Expansion by Inhibiting the Early Fibrotic Response via the MAPK-MKP-1 Pathway.

Depression is an independent risk factor for cardiovascular disease and is significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the effect of repeated social defeat (RSD) on AAA development. Eight-week-old male wild-type mice were exposed to RSD by being housed with larger CD-1 mice in a shared cage. They were subjected to vigorous physical contact. After the confirmation of depressive-like behavior, calcium chloride was applied to the infrarenal aorta of the mice. At one week, AAA development was comparable between the defeated and control mice, without any differences being observed in the accumulated macrophages or in the matrix metalloproteinase activity. At two weeks, the maximum diameter and circumference of the aneurysm were significantly increased in the defeated mice, and a significant decrease in periaortic fibrosis was also observed. Consistently, the phosphorylation of the extracellular signal-regulated kinase and the incorporation of 5-bromo-2'-deoxyuridine in the primarily cultured aortic vascular smooth muscle cells were significantly reduced in the defeated mice, which was accompanied by a substantial increase in mitogen-activated protein kinase phosphatase-1 (MKP-1). The MKP-1 mRNA and protein expression levels during AAA were much higher in the defeated mice than they were in the control mice. Our findings demonstrate that RSD enhances AAA development by suppressing periaortic fibrosis after an acute inflammatory response and imply novel mechanisms that are associated with depression-related AAA development.

Clinical results and risk factors of proton and carbon ion therapy for hepatocellular carcinoma.

BACKGROUND: The objective of this study was to evaluate the clinical outcome of proton and carbon ion therapy for hepatocellular carcinoma (HCC). METHODS: In total, 343 consecutive patients with 386 tumors, including 242 patients (with 278 tumors) who received proton therapy and 101 patients (with 108 tumors) who received carbon ion therapy, were treated on 8 different protocols of proton therapy (52.8-84.0 gray equivalents [GyE] in 4-38 fractions) and on 4 different protocols of carbon ion therapy (52.8-76.0 GyE in 4-20 fractions). RESULTS: The 5-year local control and overall survival rates for all patients were 90.8% and 38.2%, respectively. Regarding proton and carbon ion therapy, the 5-year local control rates were 90.2% and 93%, respectively, and the 5-year overall survival rates were 38% and 36.3%, respectively. These rates did not differ significantly between the 2 therapies. Univariate analysis identified tumor size as an independent risk factor for local recurrence in proton therapy, carbon ion therapy, and in all patients. Multivariate analysis identified tumor size as the only independent risk factor for local recurrence in proton therapy and in all patients. Child-Pugh classification was the only independent risk factor for overall survival in proton therapy, in carbon ion therapy, and in all patients according to both univariate and multivariate analyses. No patients died of treatment-related toxicities. CONCLUSIONS: Proton and carbon ion therapies for HCC were comparable in terms of local control and overall survival rates. These therapies may represent innovative alternatives to conventional local therapies for HCC.

Radiotherapy for Japanese elderly patients with cervical cancer: preliminary survival outcomes and evaluation of treatment-related toxicity.

PURPOSE: To examine the preliminary survival outcomes and treatment-related toxicity for elderly patients with cervical cancer treated with radiotherapy (RT). METHODS: Forty patients ≥75 years old with cervical cancer who were treated with RT were evaluated. Of these 40 patients, 25 were classified as FIGO stage I or II and 15 as stage III or IVA. Thirty-five patients were treated with radical RT (RRT), and five were treated with surgery plus adjuvant RT (S + ART). External beam radiotherapy combined with high-dose-rate intracavitary brachytherapy was performed on 31 patients who were treated with RRT and on 2 patients who were treated with S + ART because of positive vaginal surgical margins. The patients' median age was 78 years (range 75-89 years). Concurrent chemotherapy (CCT) was performed on five patients (RRT: 3, S + ART: 2). RESULTS: The median follow-up period was 20 months (range 1-85 months). Only one patient could not complete RT. The 3-year overall and disease-specific survival (OS and DSS) rates for all patients were 58 and 80%, respectively. Five patients experienced Grade 3 acute toxicity; two were treated with RRT (2/35), and three were treated with S + ART (3/5, 2 of them with CCT). Two patients experienced Grade 3 late toxicity; one was treated with RRT (1/35, with CCT) and the other was treated with S + ART (1/5). No Grade 4 or higher toxicity was experienced. CONCLUSIONS: RRT for elderly patients with cervical cancer is generally effective and safe, but severe toxicity may occur with more aggressive treatment modalities.

Roles of skull base surgery and particle radiotherapy for orbital malignant tumors involving the skull base.

PURPOSE: To investigate the oncological outcomes of orbital malignant tumors invading the skull base. METHODS: A retrospective analysis was conducted on 16 patients with orbital malignant tumors invading the skull base. Eleven patients were treated with skull base surgery, four patients were treated with particle therapies, and one patient was treated with chemoradiotherapy (CRT) as initial treatment. RESULTS: The most frequent histological type was adenoid cystic carcinoma in seven patients, followed by squamous cell carcinoma in two patients. Local recurrence occurred in two of the six surgically treated patients who did not receive postoperative radiotherapy (RT) or CRT. One of them was successfully salvaged by RT, and the other died of disease. With a median follow-up of 24 months, the 2-year overall, local control, and disease-free survival rates of all patients were 82.5%, 87.5%, and 59%, respectively. CONCLUSIONS: Patients with positive surgical margins were at risk of local recurrence. Postoperative RT should be considered for all surgically treated patients.Level of Evidence: 4.

Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation.

Maternal high-fat diet (HFD) modulates vascular remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) development. Female wild-type mice were fed an HFD or normal diet (ND). AAA was induced in eight-week-old pups using calcium chloride. Male offspring of HFD-fed dams (O-HFD) showed a significant enlargement in AAA compared with the offspring of ND-fed dams (O-ND). Positive-staining cells for tartrate-resistant acid phosphate (TRAP) and matrix metalloproteinase (MMP) activity were significantly increased in O-HFD. The pharmacological inhibition of osteoclastogenesis abolished the exaggerated AAA development in O-HFD. The in vitro tumor necrosis factor-α-induced osteoclast-like differentiation of bone marrow-derived macrophages showed a higher number of TRAP-positive cells and osteoclast-specific gene expressions in O-HFD. Consistent with an increased expression of nuclear factor of activated T cells 1 (NFATc1) in O-HFD, the nuclear protein expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor, were much lower, with significantly increased H3K27me3 marks at the promoter region. The enhancer of zeste homolog 2 inhibitor treatment restored IRF8 expression, resulting in no difference in NFATc1 and TRAP expressions between the two groups. Our findings demonstrate that maternal HFD augments AAA expansion, accompanied by exaggerated osteoclast-like macrophage accumulation, suggesting the possibility of macrophage skewing via epigenetic reprogramming.