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 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.

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.

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.

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.

Surgical outcomes of metastatic bone tumors in the extremities (Surgical outcomes of bone metastases).

BACKGROUND: Skeletal related events due to metastatic bone tumors markedly affect the activities of daily living (ADL) and quality of life (QOL) in cancer patients. We focused on multidisciplinary therapy for metastatic bone tumors. This study aimed to evaluate the outcomes of surgical treatment for metastatic bone tumors in the extremities. METHODS: We retrospectively reviewed 114 patients who underwent surgical treatment for metastatic bone tumors of the extremities between 2008 and 2019 and 69 patients were reassessed for more than 6 months after surgery. The most common primary tumor was renal, followed by lung, thyroid, and breast cancers. We assessed 69 patients' performance status (PS), Barthel Index (BI) for ADL, EuroQol 5 Dimensions (EQ-5D) for QOL, and numerical rating scale (NRS) for pain and analyzed these postoperative values relative to preoperative values using Friedman's test. The postoperative overall survival and the prognostic factors were evaluated using the Kaplan-Meier method, the log-rank test and Cox proportional hazards analysis. RESULTS: The 1-year overall survival rate was 59%, and the median survival time after surgery was 20 months. Primary tumor, visceral metastasis, and surgical procedure were risk factors correlated with overall survival. PS, BI, EQ-5D, and NRS improved at 3 months after surgery and these improvements were maintained for 6 months after surgery regardless of the surgical procedure. CONCLUSIONS: The significant factors affecting survival after surgical treatment for bone metastases included the primary tumor, presence of visceral metastases, and internal fixation without tumor resection or curettage. Surgical treatment for metastatic bone tumors effectively reduced pain and improved PS, ADL, and QOL postoperatively after 3 months.

Exosome-mediated radiosensitizing effect on neighboring cancer cells via increase in intracellular levels of reactive oxygen species.

The precise mechanism of intercellular communication between cancer cells following radiation exposure is unclear. Exosomes are membrane­enclosed small vesicles comprising lipid bilayers and are mediators of intercellular communication that transport a variety of intracellular components, including microRNAs (miRNAs or miRs). The present study aimed to identify novel roles of exosomes released from irradiated cells to neighboring cancer cells. In order to confirm the presence of exosomes in the human pancreatic cancer cell line MIAPaCa­2, ultracentrifugation was performed followed by transmission electron microscopy and nanoparticle tracking analysis (NanoSight) using the exosome­specific surface markers CD9 and CD63. Subsequent endocytosis of exosomes was confirmed by fluorescent microscopy. Cell survival following irradiation and the addition of exosomes was evaluated by colony forming assay. Expression levels of miRNAs in exosomes were then quantified by microarray analysis, while protein expression levels of Cu/Zn­ and Mn­superoxide dismutase (SOD1 and 2, respectively) enzymes in MIAPaCa­2 cells were evaluated by western blotting. Results showed that the uptake of irradiated exosomes was significantly higher than that of non­irradiated exosomes. Notably, irradiated exosomes induced higher intracellular levels of reactive oxygen species (ROS) and a higher frequency of DNA damage in MIAPaCa­2 cells, as determined by fluorescent microscopy and immunocytochemistry, respectively. Moreover, six up­ and five downregulated miRNAs were identified in 5 and 8 Gy­irradiated cells using miRNA microarray analyses. Further analysis using miRNA mimics and reverse transcription­quantitative PCR identified miR­6823­5p as a potential candidate to inhibit SOD1, leading to increased intracellular ROS levels and DNA damage. To the best of our knowledge, the present study is the first to demonstrate that irradiated exosomes enhance the radiation effect via increasing intracellular ROS levels in cancer cells. This contributes to improved understanding of the bystander effect of neighboring cancer cells.

Efficacy of Spacers in Radiation Therapy for Locally Advanced Pancreatic Cancer: A Planning Study.

BACKGROUND/AIM: We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide more effective radiation therapy for locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions. RESULTS: With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer. CONCLUSION: IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.

Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma.

BACKGROUND: To evaluate factors associated with osteoradionecrosis of the jaw (ORNJ) in patients with head and neck squamous cell carcinoma (HNSCC), focusing on jaw-related dose-volume histogram (DVH) parameters. METHODS: We retrospectively reviewed the medical records of 616 patients with HNSCC treated with curative-intent or postoperative radiation therapy (RT) during 2008-2018. Patient-related (age, sex, history of smoking or alcohol use, diabetes mellitus, performance status, pre-RT dental evaluation, pre- or post-RT tooth extraction), tumor-related (primary tumor site, T-stage, nodal status), and treatment-related (pre-RT surgery, pre-RT mandible surgery, induction or concurrent chemotherapy, RT technique) variables and DVH parameters (relative volumes of the jaw exposed to doses of 10 Gy-70 Gy [V10-70]) were investigated and compared between patients with and without ORNJ. The Mann-Whitney U test was used to compare RT dose parameters. Univariate and multivariate Cox regression analyses were used to assess factors associated with ORNJ development. Kaplan-Meier analyses were performed for cumulative ORNJ incidence estimation. RESULTS: Forty-six patients (7.5%) developed ORNJ. The median follow-up duration was 40 (range 3-145) months. The median time to ORNJ development was 27 (range 2-127) months. DVH analysis revealed that V30-V70 values were significantly higher in patients with than in those without ORNJ. In univariate analyses, primary tumor site, pre-RT mandible surgery, post-RT tooth extraction, and V60 > 14% were identified as important factors. In multivariate analyses, V60 > 14% (p = 0.0065) and primary tumor site (p = 0.0059) remained significant. The 3-year cumulative ORNJ incidence rates were 2.5% and 8.6% in patients with V60 ≤ 14% and > 14%, respectively (p < 0.0001), and 9.3% and 1.4% in patients with oropharyngeal or oral cancer and other cancers, respectively (p < 0.0001). CONCLUSIONS: V60 > 14% and oropharyngeal or oral cancer were found to be independent risk factors for ORNJ. These findings might be useful to minimize ORNJ incidence in HNSCC treated with curative RT.

[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.

Novel artifact-robust and highly visible zinc solid fiducial marker for kilovoltage x-ray image-guided radiation therapy.

PURPOSE: To develop a novel biocompatible solid fiducial marker that prevents radiopaque imaging artifacts and also maintains high imaging contrast for kilovoltage x-ray image-guided radiation therapy. METHODS: The fiducial marker was made of pure zinc. An in-house water-equivalent phantom was designed to evaluate artifacts and visibility under various simulated treatment scenarios. Image artifacts were quantitatively assessed in terms of the metal artifact index (MAI) on kilovoltage computed tomography (CT) and cone-beam CT (CBCT) scans. Marker visibility was evaluated on two types of kilovoltage planar x-ray images in terms of the contrast-to-background ratio (CBR). Comparisons with a conventional gold fiducial marker were conducted. RESULTS: The use of zinc rather than a gold marker mitigates imaging artifacts. The MAI near the zinc marker decreased by 76, 79, and 77 % in CT, and by 77 (81), 74 (80), and 79 (85) % in CBCT full-fan (half-fan) scans, when using one-, two-, and three-marker phantom settings, respectively. The high-contrast part of the zinc marker exhibited CBRs above 2.00 for 28/32 exposures under four (lung, tissue, low-density bone, and high-density bone) different simulation scenarios, making its visibility comparable to that of the gold marker (30/32 exposures with CBRs > 2.00). CONCLUSIONS: We developed a biocompatible, artifact-robust, and highly visible solid zinc fiducial marker. Although further evaluation is needed in clinical settings, our findings suggest its feasibility and benefits for kilovoltage x-ray image-guided radiation therapy.

A Comparative Assessment of Mechanisms and Effectiveness of Radiosensitization by Titanium Peroxide and Gold Nanoparticles.

The development of potentially safe radiosensitizing agents is essential to enhance the treatment outcomes of radioresistant cancers. The titanium peroxide nanoparticle (TiOxNP) was originally produced using the titanium dioxide nanoparticle, and it showed excellent reactive oxygen species (ROS) generation in response to ionizing radiation. Surface coating the TiOxNPs with polyacrylic acid (PAA) showed low toxicity to the living body and excellent radiosensitizing effect on cancer cells. Herein, we evaluated the mechanism of radiosensitization by PAA-TiOxNPs in comparison with gold nanoparticles (AuNPs) which represent high-atomic-number nanoparticles that show a radiosensitizing effect through the emission of secondary electrons. The anticancer effects of both nanoparticles were compared by induction of apoptosis, colony-forming assay, and the inhibition of tumor growth. PAA-TiOxNPs showed a significantly more radiosensitizing effect than that of AuNPs. A comparison of the types and amounts of ROS generated showed that hydrogen peroxide generation by PAA-TiOxNPs was the major factor that contributed to the nanoparticle radiosensitization. Importantly, PAA-TiOxNPs were generally nontoxic to healthy mice and caused no histological abnormalities in the liver, kidney, lung, and heart tissues.

Maternal high-fat diet exaggerates diet-induced insulin resistance in adult offspring by enhancing inflammasome activation through noncanonical pathway of caspase-11.

OBJECTIVE: Maternal high-fat diet (HFD) has been shown to promote the development of insulin resistance (IR) in adult offspring; however, the underlying mechanisms remain unclear. METHODS: Eight-week-old female wild-type mice (C57BL/6) were fed either an HFD or a normal diet (ND), one week prior to mating, and the diet was continued throughout gestation and lactation. Eight-week-old male offspring of both groups were fed an HFD for 8 weeks. RESULTS: Offspring of HFD-fed dams (O-HFD) exhibited significantly impaired insulin sensitivity compared with the offspring of ND-fed dams (O-ND). The adipocyte size of the eWAT increased significantly in O-HFD and was accompanied by abundant crown-like structures (CLSs), as well as a higher concentration of interleukin 1ß (IL-1ß) in the eWAT. Treatment with an inflammasome inhibitor, MCC950, completely abrogated the enhanced IR in O-HFD. However, ex vivo caspase-1 activity in eWAT revealed no difference between the two groups. In contrast, noncanonical inflammasome activation of caspase-11 was significantly augmented in O-HFD compared with O-ND, suggesting that membrane pore formation, but not cleavage of pro-IL-1ß by caspase-1, is augmented in O-HFD. To examine the membrane pore formation, we performed metabolic activation of bone marrow-derived macrophages (BMDMs). The percentage of pore formation assessed by ethidium bromide staining was significantly higher in BMDMs of O-HFD, accompanied by an enhanced active caspase-11 expression. Consistently, the concentration of IL-1ß in culture supernatants was significantly higher in the BMDMs from O-HFD than those from O-ND. CONCLUSIONS: These findings demonstrate that maternal HFD exaggerates diet-induced IR in adult offspring by enhancing noncanonical caspase-11-mediated inflammasome activation.

Social Stress Increases Vulnerability to High-Fat Diet-Induced Insulin Resistance by Enhancing Neutrophil Elastase Activity in Adipose Tissue.

Social stress (SS) has been linked to the development of cardiovascular disease (CVD), which is closely associated with insulin resistance (IR); however, the causal effect of SS on IR remains unclear. The 8-week-old male C57BL/6 mice were exposed to SS by housing with a larger CD-1 mouse in a shared home cage without physical contact for 10 consecutive days followed by high-fat diet (HFD) feeding. Control mice were housed in the same cage without a CD-1 mouse. After 6 weeks of HFD, insulin sensitivity was significantly impaired in stressed mice. While the percentage of classically activated macrophages in epididymal white adipose tissue (eWAT) was equivalent between the two groups, the percentage of lymphocyte antigen 6 complex locus G6D (Ly-6G)/neutrophil elastase (NE)-double positive cells markedly increased in stressed mice, accompanied by augmented NE activity assessed by ex vivo eWAT fluorescent imaging. Treatment with an NE inhibitor completely abrogated the insulin sensitivity impairment of stressed mice. In vitro NE release upon stimulation with a formyl peptide receptor 1 agonist was significantly higher in bone marrow neutrophils of stressed mice. Our findings show that SS-exposed mice are susceptible to the development of HFD-induced IR accompanied by augmented NE activity. Modulation of neutrophil function may represent a potential therapeutic target for SS-associated IR.

Stereotactic body radiotherapy in patients with lung tumors composed of mainly ground-glass opacity.

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component <50% in diameter of the tumor and no metastases were studied. Concerning histology, 32 tumors were adenocarcinoma, 1 was squamous cell carcinoma, 2 were unclassified carcinoma and 49 cases were histology-unproven but increased in size or had a positive finding in 18F-FDG positron emission tomography (PET) examination. The median tumor size was 20 mm (range, 10-41 mm). All of the patients were treated with SBRT, and the total prescribed dose at the isocenter ranged between 48 Gy in four fractions and 84 Gy in ten fractions. Median follow-up duration was 33 months. No patient had local failure nor regional lymph node failure. The 3-year rate of distant failure was 2.6%. Two patients who experienced distant metastases had a past surgical history of initial lung cancer before SBRT. The rates of cause-specific and overall survival at 3 years were 98.2 and 94.6%, respectively. Treatment-related adverse events of ≥grade 4 were not reported. Although more cases and longer follow-ups are mandatory, SBRT may be one of the radical treatment options for patients with GGN.

Oncologic and functional outcomes of transoral CO2 laser cordectomy for early glottic cancer.

OBJECTIVE: To investigate the oncological and functional outcomes of the patients treated with transoral CO2 laser cordectomy for early glottic cancer. PATIENTS AND METHODS: Fifty-five consecutive patients who underwent CO2 laser cordectomy for early glottic cancer were retrospectively reviewed. RESULTS: Overall survival, larynx preservation, and relapse free local control rates were 96%, 100%, and 91%, respectively. Five patients with local recurrences were salvaged with re-cordectomy and/or radiotherapy. In type I cordectomy, VHI-10 consistently improved during postoperative course and VHI-10 at postoperative 12months was significantly better than preoperative value (2.3 vs. 9.4, p=0.02). Perceptual grading, MPT, MFR and AC/DC also improved and were better than preoperative values. In type III cordectomy, shimmer at 12months after cordectomy was significantly better than preoperative value (14.7 vs. 9.3, p=0.007). CONCLUSIONS: These results further support the rationale of CO2 cordectomy as initial and salvage surgery for early glottic cancer.

First-In-Human Phase 1 Study of a Nonwoven Fabric Bioabsorbable Spacer for Particle Therapy: Space-Making Particle Therapy (SMPT).

PURPOSE: Surgical spacer placement (SSP) is useful in particle therapy (PT) for patients with abdominal or pelvic tumors located adjacent to normal organs. We developed a nonwoven fabric bioabsorbable spacer made of polyglycolic acid (PGA) sutures that degrades via hydrolysis. We then conducted this first-in-human phase 1 study of the combination of SSP and PT using the PGA spacer, which we termed space-making PT (SMPT). This study aimed to evaluate the safety and efficacy of SMPT in patients with unresectable malignant tumor located adjacent to normal organs. METHODS AND MATERIALS: The eligibility criteria included histologically proven malignant abdominal or pelvic tumor adjacent to the intestines, no metastasis, and no previous radiation therapy. Periodic computed tomography (CT) images were obtained before SSP and before, during, and after PT until the spacer disappeared. Treatment planning was performed for each CT image set until the end of PT, and doses for the planning target volume and organs at risk were analyzed. The thickness and volume of the PGA spacer were measured in each CT image set. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Five patients were enrolled in this study. All patients received 70.4 Gy (relative biological effectiveness) of irradiation. V95% of the planning target volume before SSP, at the beginning of PT, and at the end of PT was 82.1% ± 11.3%, 98.1% ± 1.1%, and 97.1% ± 0.8%, respectively. The PGA spacers maintained enough thickness (≥1 cm) until the end of PT and disappeared within 8 months after SSP in all patients. No grade ≥3 acute adverse events were observed. CONCLUSIONS: The SMPT is feasible and useful for abdominal or pelvic tumors adjacent to the intestines. This method may be applicable to unresectable tumors located adjacent to normal organs and may expand the indications of PT.

Dental intervention against osteoradionecrosis of the jaws in irradiated patients with head and neck malignancy: a single-arm prospective study.

BACKGROUND: The purpose of this study was to investigate the effectiveness of dental intervention before and after radiation therapy (RT) for head and neck malignancy on prevention of osteoradionecrosis (ORN) of the jaws. METHODS: This is a single-arm prospective study according to intervention protocol of prophylactic dental extraction before RT and routine follow-up after RT. The primary endpoint was the occurrence of jawbone exposure during the first 2 years after RT. RESULTS: Sixty-seven patients were assessed. Before RT, 144 teeth among 39 patients (58%) were prophylactically extracted. The occurrence of transient jawbone exposure during the first 2 years after RT was 7%. Because those jawbone exposures healed with intervention after RT, no jawbone exposure was found at 2 years after RT. CONCLUSIONS: Dental intervention both before and after RT seemed to be important to prevent ORN development. Further studies in larger cohorts are necessary.