Radiomics analysis of [18F]-fluoro-2-deoxyglucose positron emission tomography for the prediction of cervical lymph node metastasis in tongue squamous cell carcinoma.

OBJECTIVES: This study aimed to create a predictive model for cervical lymph node metastasis (CLNM) in patients with tongue squamous cell carcinoma (SCC) based on radiomics features detected by [18F]-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET). METHODS: A total of 40 patients with tongue SCC who underwent 18F-FDG PET imaging during their first medical examination were enrolled. During the follow-up period (mean 28 months), 20 patients had CLNM, including six with late CLNM, whereas the remaining 20 patients did not have CLNM. Radiomics features were extracted from 18F-FDG PET images of all patients irrespective of metal artifact, and clinicopathological factors were obtained from the medical records. Late CLNM was defined as the CLNM that occurred after major treatment. The least absolute shrinkage and selection operator (LASSO) model was used for radiomics feature selection and sequential data fitting. The receiver operating characteristic curve analysis was used to assess the predictive performance of the 18F-FDG PET-based model and clinicopathological factors model (CFM) for CLNM. RESULTS: Six radiomics features were selected from LASSO analysis. The average values of the area under the curve (AUC), accuracy, sensitivity, and specificity of radiomics analysis for predicting CLNM from 18F-FDG PET images were 0.79, 0.68, 0.65, and 0.70, respectively. In contrast, those of the CFM were 0.54, 0.60, 0.60, and 0.60, respectively. The 18F-FDG PET-based model showed significantly higher AUC than that of the CFM. CONCLUSIONS: The 18F-FDG PET-based model has better potential for diagnosing CLNM and predicting late CLNM in patients with tongue SCC than the CFM.

Reconstruction of rabbit mandibular bone defects using carbonate apatite honeycomb blocks with an interconnected porous structure.

Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects. The CO3Ap HCB were gradually resorbed and replaced by newly formed bone.

Effect of dental metal artifact conversion volume on dose distribution in head-and-neck volumetric-modulated arc therapy.

PURPOSE: During treatment planning for head-and-neck volumetric-modulated arc therapy (VMAT), manual contouring of the metal artifact area of artificial teeth is done, and the area is replaced with water computed tomography (CT) values for dose calculation. This contouring of the metal artifact areas, which is performed manually, is subject to human variability. The purpose of this study is to evaluate and analyze the effect of inter-observer variation on dose distribution. METHODS: The subjects were 25 cases of cancer of the oropharynx for which VMAT was performed. Six radiation oncologists (ROs) performed metal artifact contouring for all of the cases. Gross tumor volume, clinical target volume, planning target volume (PTV), and oral cavity were evaluated. The contouring of the six ROs was divided into two groups, small and large groups. A reference RO was determined for each group and the dose distribution was compared with those of the other radiation oncologists by gamma analysis (GA). As an additional experiment, we changed the contouring of each dental metal artifact area, creating enlarged contours (L), reduced contours (S), and undrawn contours (N) based on the contouring by the six ROs and compared these structure sets. RESULTS: The evaluation of inter-observer variation showed no significant difference between the large and small groups, and the GA pass rate was 100%. Similar results were obtained comparing structure sets L and S, but in the comparison of structure sets L and N, there were cases with pass rates below 70%. CONCLUSIONS: The results show that the artificial variability of manual artificial tooth metal artifact contouring has little effect on the dose distribution of VMAT. However, it should be noted that the dose distribution may change depending on the contouring method in cases where the overlap between PTV and metal artifact areas is large.

Fabrication and evaluation of carbonate apatite-coated calcium carbonate bone substitutes for bone tissue engineering.

Carbonate apatite-coated calcium carbonate (CO3 Ap/CaCO3 ) was fabricated through a dissolution-precipitation reaction using CaCO3 granules as a precursor to accelerate bone replacement based on superior osteoconductivity of the CO3 Ap shell, along with Ca2+ release from the CaCO3 core and quicker resorption of the CaCO3 core. In the present study, CaCO3 , 10% CO3 Ap/CaCO3 , 30% CO3 Ap/CaCO3 , and CO3 Ap granules were fabricated and examined histologically to evaluate their potential as bone substitutes. Larger contents of CaCO3 in the granules resulted in higher Ca2+ release and promoted cell proliferation of murine preosteoblasts at 6 days compared with CO3 Ap. Interestingly, in a rabbit femur defect model, 10% CO3 Ap/CaCO3 induced significantly higher new bone formation and higher material resorption compared with CO3 Ap at 8 weeks. Nevertheless, CO3 Ap showed a superior osteoconductive potential compared with 10% CO3 Ap/CaCO3 at 8 weeks. All tested granules were most likely resorbed by cell mediation including multinucleated giant cell functions. Therefore, we conclude that CO3 Ap/CaCO3 has a positive potential for bone tissue engineering based on well-controlled calcium release, bone formation, and material resorption.

Compositional and histological comparison of carbonate apatite fabricated by dissolution-precipitation reaction and Bio-Oss®.

Carbonate apatite (CO3Ap) is an inorganic component of bone. This study aimed to compare the composition and tissue response to of CO3Ap (CO3Ap-DP) fabricated by the dissolution-precipitation reaction using calcite as a precursor and Bio-Oss®, which is widely used in orthopedic and dental fields as a synthetic bone substitute. X-ray diffraction and Fourier transform infrared results showed that CO3Ap-DP and Bio-Oss® were both B-type carbonate apatite with low crystallinity. The average sizes of CO3Ap-DP and Bio-Oss® granules were 450 ± 58 and 667 ± 168µ m, respectively, and their carbonate contents were 12.1 ± 0.6 and 5.6 ± 0.1 wt%, respectively. CO3Ap-DP had a larger amount of CO3 than Bio-Oss® but higher crystallinity than Bio-Oss®. When a bone defect made at the femur of rabbits was reconstructed with CO3Ap-DP and Bio-Oss®, CO3Ap-DP granules were partially replaced with bone, whereas Bio-Oss® remained at 8 weeks after implantation. CO3Ap-DP granules elicited a significantly larger amount of new bone formation at the cortical bone portion than Bio-Oss® at 4 weeks after the implantation. The results obtained in the present study demonstrated that CO3Ap-DP and Bio-Oss® showed different behavior even though they were both classified as CO3Ap. The CO3 content in CO3Ap played a more important role than the crystallinity of CO3Ap for replacement to bone and high osteoconductivity.

Prevalence and imaging characteristics of palatine tonsilloliths evaluated on 2244 pairs of panoramic radiographs and CT images.

OBJECTIVES: Palatine tonsilloliths incidentally detected on diagnostic imaging should be differentiated from pathologic calcifications to enable correct diagnosis and treatment. The aim of this study is to clarify the prevalence and imaging characteristics of palatine tonsilloliths on panoramic radiographs. MATERIALS AND METHODS: We retrospectively reviewed 2244 individuals who underwent pairs of consecutive panoramic radiography and computed tomography (CT) of the head and neck region. The imaging characteristics of palatine tonsilloliths on panoramic radiography were compared with the findings from CT, which was considered the gold standard. RESULTS: Tonsilloliths were detected in 300 (13.4 %) and 914 (40.7 %) of the 2244 individuals on panoramic radiographs and CT, respectively. On panoramic radiographs, tonsilloliths were superimposed over the ramus of the mandible at the level coincident with and inferior to the soft palate in 176 (7.8 %) and 90 (4.0 %) individuals, respectively. Tonsilloliths were also superimposed over the surrounding soft tissue inferior to the body of the mandible, postero-inferior to the angle of the mandible, and posterior to the ramus of the mandible in 33 (1.5 %), 26 (1.2 %), and 28 (1.3 %) individuals, respectively. A significant correlation was observed between the detectability on panoramic radiographs and the size (Spearman r = 1.000) and number (Spearman r = 0.991) of tonsilloliths, as revealed by CT images. CONCLUSIONS: The present results suggest that tonsilloliths are commonly detected on panoramic radiographs. Furthermore, they can be superimposed on both the mandible and the surrounding soft tissue. CLINICAL RELEVANCE: Clinicians should include tonsilloliths among the differential diagnoses when calcified bodies are detected on panoramic radiographs.

Neuroendocrine tumor in the mandible: a case report with imaging and histopathologic findings.

Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are mostly observed in the gastrointestinal tract, pancreas, and lungs. NETs in the oral and maxillofacial region are extremely rare. We report a case of a 59-year-old woman with an NET in the mandible. The patient did not show any symptoms except for remarkable swelling and bleeding. The lesion appeared as a radiolucent honeycomb abnormality with bone destruction on panoramic radiography. The histopathologic diagnosis following a biopsy was NET. Contrast-enhanced computed tomography (CT), 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT), and adrenal scintigraphy-labeled meta-iodobenylguanidine were the modalities added to identify the primary site. Multiple lesions were confirmed in the gastrointestinal tract. Endoscopy was performed to identify the lesions, and several lesions were observed protruding from the mucous membranes. However, the endoscopy specimens did not yield an accurate diagnosis because adequate samples were not acquired. Blood and urine tests revealed no functional activity caused by the tumors. Although the origin was not histopathologically confirmed with endoscopy, this patient was situationally diagnosed with nonfunctional NET originating from the duodenum, as demonstrated by the metastases in the mandible.

Prevalence and imaging characteristics of palatine tonsilloliths detected by CT in 2,873 consecutive patients.

AIM: Tonsilloliths are calcified structures that develop in tonsillar crypts. They are commonly detected in daily clinical practice. The prevalence of tonsilloliths was 16 to 24% in previous reports, but it is inconsistent with clinical experience. The aim of this study is to clarify the prevalence, number, and size distribution of tonsilloliths using computed tomography (CT) in a relatively large number of patients. MATERIALS AND METHODS: We retrospectively reviewed the scans of 2,873 patients referred for CT examinations with regard to tonsilloliths. RESULTS: Palatine tonsilloliths were found in 1,145 out of 2,873 patients (39.9%). The prevalence of tonsilloliths increased with age, and most commonly in patients of ages 50-69. The prevalence in the 30s and younger was statistically lower than in the 40s and older (P < 0.05). The number of tonsilloliths per palatine tonsil ranged from one to 18. The size of the tonsilloliths ranged from 1 to 10 mm. For the patients with multiple CT examinations,the number of tonsilloliths increased in 51 (3.9%) and decreased in 84 (6.5%) of the tonsils. CONCLUSIONS: As palatine tonsilloliths are common conditions, screenings for tonsilloliths during the diagnosis of soft tissue calcifications should be included in routine diagnostic imaging.

Shielding effect of a customized intraoral mold including lead material in high-dose-rate 192-Ir brachytherapy for oral cavity cancer.

A high-dose-rate (HDR) 192-Ir brachytherapy using a customized intraoral mold is effective for superficial oral cavity cancer, and the surrounding normal tissue is kept away from the radioactive source with gauze pads and/or mouth piece for reducing the dose on the normal tissues. In the Tokushima university hospital, the mold has a lead shield which utilizes the space prepared with sufficient border-molding by a specific dental technique using modeling compound. In HDR 192-Ir brachytherapy using a lead shielded customized intraoral mold, there are no reports measuring the absorbed dose. The purpose of the present study is to measure the absorbed dose and discuss the optimum thickness of lead in HDR 192-Ir brachytherapy using a customized intraoral mold with lead shield using a 1 cm thickness mimic mold. The thickness of lead in the mold could be changed by varying the arrangement of 0.1 cm thickness sheet of the acrylic resin plate and lead. The measured doses at the lateral surface of the mold with thermo-luminescence dosimeter were reduced to 1.12, 0.79, 0.57, 0.41, 0.31, 0.24 and 0.19 Gy and the ratios to the prescription dose were reduced to 56, 40, 29, 21, 16, 12 and 10 percent as lead thickness increased from 0 to 0.6 cm in 0.1 cm increments, respectively. A 0.3 cm thickness lead was considered to be required for a 1 cm thickness mold, and it was necessary to thicken the lead as much as possible with the constraint of limited space in the oral cavity, especially at the fornix vestibule.

High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique.

OBJECTIVE: The purpose of this study was to introduce a novel customized intraoral mold treatment for maxillary gingival carcinoma (UGC). STUDY DESIGN: Two patients with UGC were treated as salvage therapy using this technique. The mold was designed to keep normal soft tissues adjacent to the tumor away from the radioactive source as much as possible, and it was shielded by lead. The radiation dose on the buccal mucosa and tongue was measured at the inner and outer surfaces of the intraoral mold before starting high-dose-rate brachytherapy by the remote afterloading system, and was reduced to almost one tenth. RESULTS: The patient had no recurrence and no severe adverse effects on the normal soft tissue adjacent to the tumor until the end of the follow-up period. CONCLUSION: High-dose-rate brachytherapy using the novel customized intraoral mold might be a treatment option of not only salvage therapy, but definitive therapy of UGC.

Effective bladder preservation strategy with low-dose radiation therapy and concurrent intraarterial chemotherapy for muscle-invasive bladder cancer.

PURPOSE: The aim of this study was to evaluate retrospectively the toxicity and response, bladder preservation, and survival of patients with muscle-invasive bladder cancer treated with multimodality therapy consisting of low-dose radiation therapy (RT) and concurrent intraarterial chemotherapy (IACT). METHODS AND MATERIALS: . Between November 1999 and July 2005, a total of 27 consecutive, previously untreated patients with muscle-invasive bladder cancer underwent transurethral bladder tumor resection followed by concurrent low-dose RT and IACT. Patients who achieved a complete response (CR) were followed up closely without further therapy, and patients who did not achieve a CR underwent further treatment. RESULTS: Complete response was achieved in 22 of 27 patients (81%). Of these 22 patients, 7 developed recurrences, and 3 died of their disease. In five patients who did not achieve CR, one died from bone metastases. The 3-year overall survival rate was 81%, with a median follow-up time of 27 months; and 22 of 27 patients (81%) with a preserved bladder were tumor-free at the last follow-up. Three patients (11%) developed grade 3 acute hematological toxicity. CONCLUSION: Multimodality therapy consisting of low-dose RT and concurrent IACT for muscle-invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation and minimal adverse effects.

Can Kampo therapy prolong the life of cancer patients?

Our policy regarding the performance of radiotherapy to squamous cell carcinoma of the uterine cervix has not changed since 1969. We have already reported the treatment results which were as good as those from other institutions. Since 1978, Kampo therapy was first introduced in the treatment of cancer patients in dealing with problems such as the side effects of radiotherapy and chemotherapy and various types of general malaise. We analyzed our treatment results in order to re-evaluate the chemo-radiotherapy in combination with Kampo. Survival rates for 5, 10 and 15 years, respectively, were 90.9%, 71.6% and 71.6% for Stage IB, 78.9%, 61.8% and 41.8% for Stage II, 62.3%, 49.1% and 41.2% for Stage III and 53.1%, 36.5% and 16.7% for Stage IV. The Kampo significantly extended the survival of patients with uterine cervical cancer. We intend to perform further research with more patients to explore how this therapy contributes to the prolonging of patients survival.

Radiation therapy for cervical cancer in the elderly.

OBJECTIVE: To evaluate the long-term results of radical radiation therapy (RT) for cervical cancer in elderly patients. METHODS: We reviewed the clinical records of 727 patients with cervical cancer who underwent radical RT at the Tokushima University Hospital and compared the treatment results of three age groups: /=75 years (older group [OG], 132 patients). RESULTS: At the last follow-up, 155 YG (46%), 77 YOG (30%), and 48 OG patients (36%) had died of cervical cancer; the median follow-up periods were 82, 87, and 68 months, respectively. The 5-/10-year disease-specific survival rates were 60%/52% in YG, 76%/68% in YOG, and 66%/57% in OG. Differences between OG and the other groups were not significant. The 5-/10-year disease-specific survival rate of YOG was significantly superior to that of YG (p<0.001). Clinical stage was the only significant prognostic variable (p<0.001). Late radiation morbidity of grades 2-4 in the bladder and/or rectum occurred in 22% of YG, 31% of YOG, and 8% of OG patients. CONCLUSIONS: RT was well tolerated in elderly patients, and age was not a significant prognostic factor. In the management of cervical cancer, advanced age is not a contraindication to radical RT.

Pelvic bone complications following radiation therapy of gynecologic malignancies: clinical evaluation of radiation-induced pelvic insufficiency fractures.

OBJECTIVE: To investigate the incidence, clinical and imaging finding of insufficiency fractures (IF) of the female pelvis following radiation therapy. METHODS: We reviewed the radiation oncology records of 158 patients with gynecologic malignancies who underwent external beam radiation therapy of the whole pelvis between April 1993 and March 2004. All patients underwent computed tomography (CT) scan every 6 months in follow-up after radiation therapy and magnetic resonance imaging (MRI) and radionuclide bone scan were added when the patients complained of a pelvic pain. RESULTS: Eighteen of 158 patients (11.4%) developed IF in the irradiated field with a median interval of 6 months (range 3-51) from the completion of external beam radiation therapy. The cumulative incidence of symptomatic IF at 5 years calculated with Kaplan-Meyer methods was 13%. Median age of the patients who developed IF was 70 years (range 48-88), and all of them were postmenopausal. IF occurred in the sacloiliac joints, upper limb of pubic bone, acetabulum, sacral body and 5th lumbar vertebra. Twelve of 18 patients had multiple lesions and 8 had symmetric longitudinal fracture lines parallel to the sacroiliac joints. Avoidance of weight bearing by bed rest and analgesics provided good pain relief in all patients, although symptoms lasted from 3 to 20 months. CONCLUSIONS: Radiation-induced pelvic IF following radiation therapy for gynecologic malignancies were frequently observed in the postmenopausal patients within 1 year after external beam radiation therapy. Symmetric fractures of the both sacroiliac joints were the characteristic pattern of pelvic IF. Knowledge of characteristic imaging pattern of IF is essential in order to rule out the bone metastasis. Therapy recommendations are conservative with analgesics.

Chemoradiation therapy for cervical cancer: toxicity of concurrent weekly cisplatin.

PURPOSE: To retrospectively evaluate the toxicity of concurrent weekly cisplatin and radiation therapy (RT) for locally advanced cervical cancer. MATERIALS AND METHODS: Between April 2001 and December 2004, 21 consecutive previously untreated patients with locally advanced cervical cancer were treated with concurrent chemoradiation therapy (CCRT) at the Tokushima University Hospital. Clinical stages were II: 5, III: 15, IVA: 1. External beam radiation therapy (EBRT) was delivered with 10 MV X-rays, 2 Gy fraction per day; total dose to the whole pelvis was 50 Gy. Iridium-192 high-dose-rate (HDR) intracavitary radiation therapy was performed with 10-30 Gy (median, 24 Gy) targeted at point A. Concurrent chemotherapy consisted of cisplatin, administered weekly at a dose of 40 mg/m2 for patients who were younger than 65 years and 30 mg/m2 for those 65 years or over. A maximum single dose of cisplatin, up to 70 mg/body, was administered in 5 cycles during EBRT. RESULTS: A total of 86 cycles of cisplatin were administered to the 21 patients, with a median of 4 cycles (range, 2-5). Severe hematological toxicity occurred in 18 patients (86%), including grade 3 in 17 patients (81%) and grade 4 in one patient (4.8%). Moderate or severe gastrointestinal toxicity occurred in 11 patients (52%), including grade 2 in 10 patients (48%) and grade 3 in one patient (4.8%). The grades of hematological toxicity were significantly greater in the 40 mg/m2 group than in the 30 mg/m2 group. All of the patients who were administered 40 mg/m2 of cisplatin developed grade 3 or greater hematological toxicity, including one patient with grade 4 toxicity. In the 30 mg/m2 group, 3 of 10 patients developed less than grade 3 toxicity, and all patients completed radiation therapy without interruption. CONCLUSION: The incidence of severe acute hematological toxicity was significantly higher in this study than in previously reported randomized controlled trials (RCTs), especially in the group of 40 mg/m2 cisplatin. A dose of 30 mg/m2 of cisplatin was considered to be feasible in weekly cisplatin and radiation therapy.