Optimal threshold of a control parameter for tomotherapy respiratory tracking: A phantom study.

BACKGROUND: Radixact Synchrony® , a real-time motion tracking and compensating modality, is used for helical tomotherapy. Control parameters are used for the accurate application of irradiation. Radixact Synchrony® uses the potential difference, which is an index of the accuracy of the prediction model of target motion and is represented by a statistical prediction of the 3D distance error. Although there are several reports on Radixact Synchrony® , few have reported the appropriate settings of the potential difference threshold. PURPOSE: This study aims to determine the optimal threshold of the potential difference of Radixact Synchrony® during respiratory tumor-motion-tracking irradiation. METHODS: The relationship among the dosimetric accuracy, motion tracking accuracy, and control parameter was evaluated using a moving platform, a phantom with a basic respiratory model (the fourth power of a sinusoidal wave), and several irregular respiratory model waveforms. The dosimetric accuracy was evaluated by gamma analysis (3%, 1 mm, 10% dose threshold). The tracking accuracy was measured by the distance error of the difference between the tracked and driven positions of the phantom. The largest potential difference for 95% of treatment time was evaluated, and its correlation with the gamma-pass ratio and distance error was investigated. The optimal threshold of the potential difference was determined by receiver operating characteristic (ROC) analysis. RESULTS: A linear correlation was identified between the potential difference and the gamma-pass ratio (R = -0.704). A linear correlation was also identified between the potential difference and distance error (R = 0.827). However, as the potential difference increased, it tended to underestimate the distance error. The ROC analysis revealed that the appropriate cutoff value of the potential difference was 3.05 mm. CONCLUSION: The irradiation accuracy with motion tracking by Radixact Synchrony® could be predicted from the potential difference, and the threshold of the potential difference should be set to ∼3 mm.

Clinicopathological features of adrenal malignancies: Analysis of hospital-based cancer registry data in Japan.

OBJECTIVE: To identify the clinicopathological features of adrenal malignancies and analyze the prognoses of patients with adrenal cortical carcinoma (ACC) and malignant pheochromocytoma (MPCC). PATIENTS AND METHODS: We used a hospital-based cancer registry data in Japan to extract cases of adrenal malignancies that were histologically confirmed, diagnosed, and initially treated from 2012-2015. For survival analysis, we used data from the 2008-2009 cohort to estimate 5-year overall survival (OS) by the Kaplan-Meier method. RESULTS: A total of 989 adrenal malignancies were identified in the 2012-2015 cohort. The most common histologies were ACC (26.4%), diffuse large B-cell lymphoma (DLBCL; 25.4%), neuroblastoma (22.2%), and MPCC (11.9%). While most ACC and MPCC patients were in their 60s, DLBCL patients accounted for 61.5% of adrenal malignancies in the over-70 cohort. Among ACC patients with clinical staging data, 46.3% of patients were stage IV. Although surgery was a chief strategy for all stages, younger patients tended to receive combination therapy, including surgery and chemotherapy or hormone therapy. In the 2008-2009 cohort, the 5-year OS rates of ACC (n = 49) and MPCC (n = 23) patients were 56.2% and 86.4% while ACC patients without surgery had 1- and 2-year OS rates of 25.0% and 12.5%. CONCLUSION: In Japan, DLBCL accounted for the majority of adrenal malignancies in older patients. Despite advanced staging, ACC patients were mainly treated with surgery and their prognosis was not satisfactory. Such epidemiological data may be useful in considering initial management strategies.

O-arm Navigation-Guided Surgical Resection and Posterior Fixation for a Large Sacral Schwannoma.

Sacral schwannoma is a rare tumor with relatively few symptoms; it thus tends to be large at diagnosis and is challenging to treat surgically. We present the case of a 12-year-old girl with a large sacral schwannoma that was successfully surgically resected using O-arm navigation in a two-stage operation. First, we performed tumor resection from the posterior aspect with assisted O-arm navigation. One week later, resection from the anterior aspect was conducted with posterior spinopelvic fixation and fibula graft. We performed partial resection of the tumor from the anterior and posterior aspects as much as possible. O-arm navigation contributed to precise and safe tumor resection and implant insertion.

Couch modeling optimization for tomotherapy planning and delivery.

We sought to validate new couch modeling optimization for tomotherapy planning and delivery. We constructed simplified virtual structures just above a default setting couch through a planning support system (MIM Maestro, version 8.2, MIM Software Inc, Cleveland, OH, USA). Based on ionization chamber measurements, we performed interactive optimization and determined the most appropriate physical density of these virtual structures in a treatment planning system (TPS). To validate this couch optimization, Gamma analysis and these statistical analyses between a three-dimensional diode array QA system (ArcCHECK, Sun Nuclear, Melbourne, FL, USA) results and calculations from ionization chamber measurements were performed at 3%/2 mm criteria with a threshold of 10% in clinical QA plans. Using a virtual model consisting of a center slab density of 4.2 g/cm3 and both side slabs density of 1.9 g/cm3 , we demonstrated close agreement between measured dose and the TPS calculated dose. Agreement was within 1% for all gantry angles at the isocenter and within 2% in off-axis plans. In validation of the couch modeling in a clinical QA plan, the average gamma passing rate improved approximately 0.6%-5.1%. It was statistically significant (P < 0.05) for all treatment sites. We successfully generated an accurate couch model for a TomoTherapy TPS by interactively optimizing the physical density of the couch using a planning support system. This modeling proved to be an efficient way of correcting the dosimetric effects of the treatment couch in tomotherapy planning and delivery.

[Metachronous Development of Mantle Cell Lymphoma during Active Surveillance in a Patient with Stage I Testicular Cancer].

A 78-year-old man presented with swelling of para-aortic and left iliac lymph nodes (LNs). He had undergone left high orchiectomy 10 years ago. He was diagnosed with stage I seminoma, and was managed with active surveillance. Eight years later, the follow-up computed tomography (CT) revealed para-aortic LN swelling, but the patient refused further treatment. He complained of left lower extremity edema 10 years after orchiectomy. CT showed enlargement of both LNs, especially, diameter of left iliac lymph nodes was up to 9 cm. He was referred to our hospital. LDH was slightly increased to 261 IU/1, but α-fetoprotein, and total and free beta human chorionic gonadotropin were within normal limits. Results of pathological review of the testicular tumor was also seminoma. The treatment with etoposide and cisplatin (EP) was started under the diagnosis of late relapse of seminoma. However, CT after 1 course of EP showed no shrinkage of LN metastases. At this time, soluble interleukin-2 receptor (sIL-2R) was elevated up to 5,090 U/ml (normal range: 613 U/ml). Needle biopsy from pelvic LN was performed on suspicion of metachronous malignant lymphoma. The pathological diagnosis was mantle cell lymphoma. The patient was transferred to the department of hematology, and treated successfully with rituximab and bendamustine. When LN swelling is seen after long-term active surveillance, there is a possibility of late relapse. However, metachronous malignant lymphoma also should be considered in an elderly patient.

Stereotactic Body Radiation Therapy for Prostate Cancer Using Tomotherapy With Synchrony Fiducial Tracking.

Numerous prospective and retrospective studies have demonstrated the efficacy and safety of stereotactic body radiation therapy (SBRT) for prostate cancer. Since SBRT utilizes a very tight margin, management of intrafraction prostate motion is necessary. As a real-time motion tracking and correction system (Synchrony; Accuray, Sunnyvale, CA) has been introduced in the newer platform of tomotherapy (Radixact; Accuray), Radixact can deliver tracking SBRT. In the case report, we present the first clinical experience with prostate SBRT using tomotherapy with Synchrony fiducial tracking.

Seronegative Ocular Myasthenia Gravis in an Older Woman With Transient Dizziness and Diplopia.

Myasthenia gravis (MG) is a neuromuscular junction disease caused by an autoimmune response against cholinergic receptors. The challenge in diagnosing MG in older patients is the variety of symptoms and clinical manifestations. Clinical reasoning, precise history, and physical examination leading to a logical diagnosis should be performed to diagnose seronegative MG. We report a case of seronegative MG with the chief complaint of dizziness in a 91-year-old female. Despite the complicated clinical course, continuous clinical reasoning and testing can lead to appropriate diagnosis and treatment. As the dizziness symptoms in this older patient could not be explained by chronic or peripheral symptoms alone, ocular MG was considered as a possible diagnosis based on her history and physical examination findings. Appropriate diagnosis of seronegative ocular MG reactivated older patients with a good quality of life. In community medicine, where the behavior of elderly patients varies, it is important to improve the accuracy of diagnosis and treatment through appropriate history and physical examination, which will lead to longer home life in older patients.

[Usefulness of an Ultrasound System with Automatic Bladder Urine Volume Measurement Using Artificial Intelligence Technology in Radiotherapy].

PURPOSE: We aimed to investigate the usefulness of iViz air ver.4 Convex (FUJIFILM, Tokyo) as a tool to determine the bladder capacity before prostate radiotherapy by comparing it with the existing BladderScan BVI 6100 (Verathon Inc., Bothell, Washington). METHODS: We investigated the usefulness of iViz air as a tool to determine the bladder capacity before prostate radiotherapy by comparing it with the current BladderScan. RESULTS: The absolute value of each error rate was approximately 30.9%±27.2% and 26.4%±18.9% for the BladderScan and iViz air, respectively, with no significant differences between the instruments (p=0.16). Evaluated by urine volume, the mean error rates for bladder volumes >50 ml were 26.9%±19.0% and 26.1%±18.5% for the Bladder Scan and iViz air, respectively, with no significant differences (p=0.56). However, the BladderScan and iViz air had significantly higher error rates of 89.5%±52.5% and 31.5%±25.1%, respectively, if the bladder volume was <50 ml (p=0.005). CONCLUSION: The iViz air has limited measurement error to confirm images, especially in limited volumes, suggesting that it is a useful bladder capacity measurement device in performing prostate radiotherapy.

Characteristics of a bolus created using thermoplastic sheets for postmastectomy radiation therapy.

This study applied a "shell bolus," an immobilizing thermoplastic shell locally thickened with extra layers over the radiation target, during postmastectomy radiation therapy (PMRT). We performed ion chamber and film measurements for a solid water phantom for thermoplastic sheets and a gel bolus for dosimetric characterization using a 6-MV X-ray flattening-filter-free (FFF) beam. The air gaps between the body surface for the gel and shell bolus were measured using computed tomography (CT) images in patients who underwent PMRT. This included seven and 13 patients treated with the gel and shell boluses, respectively. A comparison of the dose differences between a 10-mm gel bolus and a 9.6-mm-thick thermoplastic sheet at the surface and 5 cm below the surface showed a 4.2% higher surface dose and 0.5% lower dose at 5-cm depth for the thermoplastic sheet compared to those for the gel bolus. The mean (p = 0.029) and maximum (p < 0.001) air gaps of the shell bolus were significantly thinner than those of the gel bolus. Thus, the shell bolus provided a close fit and robust bolus effect. In addition, the shell bolus reduced respiratory motion and eliminated the need for skin marking. Therefore, this system can be effectively used as a bolus for PMRT.

A first report of tumour-tracking radiotherapy with helical tomotherapy for lung and liver tumours: A double case report.

There are only a limited number of previous reports on clinical cases using tumour tracking with tomotherapy. Therefore, we present two cases of patients treated with tumour tracking with tomotherapy. First, a 74-year-old man with an inoperable lung cancer type T1bN0M0 underwent stereotactic body radiotherapy at a total dose of 48 Gy in four fractions. Second, a 68-year-old man with hepatocellular carcinoma with a portal venous tumour thrombosis and history of liver stereotactic body radiotherapy with fiducial marker implantation received radiotherapy at a total dose of 48 Gy in 20 fractions. The results of patient-specific quality assurance and tracking radiotherapy were sufficient to irradiate tumours. Tumour tracking with tomotherapy successfully delivered radiation in a total of 24 treatment fractions in both patients. Tumour tracking with tomotherapy is feasible in lung and liver cancer treatment. This study's findings suggest the clinical use of tumour tracking with tomotherapy.

Ro 90-7501 Is a Novel Radiosensitizer for Cervical Cancer Cells that Inhibits ATM Phosphorylation.

BACKGROUND/AIM: Ro 90-7501 has been reported as an inhibitor of the amyloid ß42 fibril assembly that is associated with Alzheimer's disease. The present study aimed to elucidate the radiosensitizing effects of Ro 90-7501 and focused on ATM signaling after irradiation. MATERIALS AND METHODS: Clonogenic survival, apoptosis, and cell-cycle assays as well as western blotting were performed in HeLa cells treated with irradiation and Ro 90-7501. Tumor growth delay assay was also performed using BALB/c-nu mice. RESULTS: The combination of irradiation with Ro 90-7501 showed significant radiosensitizing effects in clonogenic survival and tumor growth delay assays. Ro 90-7501 significantly increased apoptosis and impaired cell cycle after irradiation. Western blotting showed that Ro 90-7501 suppressed the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation. CONCLUSION: Ro 90-7501 inhibits DNA damage response by inhibiting ATM and has significant radiosensitizing effects on cervical cancer cells.

[Effects of antisense oligo DNA on the antimicrobial activity of reactive oxygen intermediates and antimycobacterial agents against Mycobacterium avium complex].

There has not yet been systematic studies which attempt to elucidate detailed profiles of the interaction between antimicrobial drugs and macrophage microbicidal mechanisms. We examined the effects of antisense oligo DNAs (AsDNAs) against oxyR and ahpC on the susceptibility of Mycobacterium avium complex (MAC) to the H2O2-halogenation system and combined antimycobacterial drugs [clarithromycin (CAM) + rifampicin (RFP)], both separately and in combination. It was found that AsDNA treatment of MAC did not affect the susceptibility of the organisms to any of the antimicrobial systems tested. Since the present AsDNAs did not efficiently reduce the expression of AhpC mRNA, attempts to increase bacterial uptake of AsDNAs are necessary to achieve significant increase in the drug susceptibility of MAC organisms due to AsDNA treatment.

Combined effects of ATP on the therapeutic efficacy of antimicrobial drug regimens against Mycobacterium avium complex infection in mice and roles of cytosolic phospholipase A2-dependent mechanisms in the ATP-mediated potentiation of antimycobacterial host resistance.

ATP, which serves as a mediator of intramacrophage signaling pathways through purinoceptors, is known to potentiate macrophage antimycobacterial activity. In this study we examined the effects of ATP in potentiating host resistance to Mycobacterium avium complex (MAC) infection in mice undergoing treatment with a drug regimen using clarithromycin and rifamycin and obtained the following findings. First, the administration of ATP in combination with the clarithromycin and rifamycin regimen accelerated bacterial elimination in MAC-infected mice without causing changes in the histopathological features or the mRNA expression of pro- or anti-inflammatory cytokines from those in the mice not given ATP. Second, ATP potentiated the anti-MAC bactericidal activity of macrophages cultivated in the presence of clarithromycin and rifamycin. This effect of ATP was closely related to intracellular Ca2+ mobilization and was specifically blocked by a cytosolic phospholipase A2 (cPLA2) inhibitor, arachidonyl trifluoromethylketone. Third, intramacrophage translocation of membranous arachidonic acid molecules to MAC-containing phagosomes was also specifically blocked by arachidonyl trifluoromethylketone. In the confocal microscopic observation of MAC-infected macrophages, ATP enhanced the intracellular translocation of cPLA2 into MAC-containing phagosomes. These findings suggest that ATP increases the host anti-MAC resistance by potentiating the antimycobacterial activity of host macrophages and that the cPLA2-dependent generation of arachidonic acid from the phagosomal membrane is essential for such a phenomenon.

Interaction of antimycobacterial drugs with the anti-Mycobacterium avium complex effects of antimicrobial effectors, reactive oxygen intermediates, reactive nitrogen intermediates, and free fatty acids produced by macrophages.

The profiles of the interaction of antimycobacterial drugs with macrophage (MPhi) antimicrobial mechanisms have yet to be elucidated in detail. We examined the effects of various antimycobacterial drugs on the anti-Mycobacterium avium complex (MAC) antimicrobial activity of reactive oxygen intermediates (ROIs), especially of an H(2)O(2)-halogen (H(2)O(2)-Fe(2+)-NaI)-mediated bactericidal system, reactive nitrogen intermediates (RNIs), and free fatty acids (FFAs), which are known as central antimicrobial effectors of host MPhis against mycobacterial pathogens. We have found that certain drugs, such as rifampin (RIF), rifabutin (RFB), isoniazid (INH), clofazimine (CLO), and some fluoroquinolones, strongly or moderately reduced the anti-MAC activity of the H(2)O(2)-Fe(2+)-NaI system, primarily by inhibiting the generation of hypohalite ions and in part by interfering with the halogenation reaction of bacterial cell components due to the H(2)O(2)-Fe(2+)-NaI system. This phenomenon is specific to the H(2)O(2)-Fe(2+)-NaI system, since these drugs did not reduce the anti-MAC activity of RNIs and FFAs. From the perspective of the chemotherapy of MAC infections, the present findings indicate an important possibility that certain antimycobacterial drugs, such as rifamycins (RIF and RFB), INH, CLO, and also some types of fluoroquinolones, may interfere with the ROI-mediated antimicrobial mechanisms of host MPhis against intracellular MAC organisms.

Intramacrophage passage of Mycobacterium tuberculosis and M. avium complex alters the drug susceptibilities of the organisms as determined by intracellular susceptibility testing using macrophages and type II alveolar epithelial cells.

Mycobacterium tuberculosis and M. avium complex strains given intramacrophage passage (I-type) were compared with those cultured in a liquid medium (E-type) for their drug susceptibilities when they were replicating in Mono-Mac-6 macrophages or A-549 cells. Their intracellular susceptibilities to rifalazil, clarithromycin, and levofloxacin were decreased more in I-type organisms than in E-type organisms, except that their rifalazil susceptibility inside A-549 cells was markedly increased in I-type organisms.

Comparative profiles of intramacrophage behavior of Mycobacterium tuberculosis and Mycobacterium avium complex with different levels of virulence.

Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) strains with different levels of virulence in mice were examined for profiles of interaction with murine peritoneal macrophages (Mphis). Their growth rates in Mphis were in these orders: H37Ra strain (attenuated) > H37Rv strain (virulent) for MTB, and N-260 strain (moderate virulence) > MAC N-444 strain (low virulence) for MAC. MTB but not MAC caused the necrotic death of host Mphis in terms of increased release of lactate dehydrogenase from infected Mphis. The MTB H37Ra strain induced a greater production of reactive nitrogen intermediates (RNI) by Mphis than the MTB H37Rv strain did. However, this phenomenon was not observed with MAC, implying less important roles of RNI in the expression of Mphi antimicrobial activity against MAC organisms.