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Ken Yoshida - Top 30 Publications

Long-term Outcomes of a Dose-reduction Trial to Decrease Late Gastrointestinal Toxicity in Patients with Prostate Cancer Receiving Soft Tissue-matched Image-guided Intensity-modulated Radiotherapy.

We experienced an unexpected high incidence of gastrointestinal (GI) toxicity in patients undergoing image-guided intensity-modulated radiotherapy (IG-IMRT) using helical tomotherapy in our initial 2.2 Gy/fraction schedule for prostate cancer; hence, a dose-reduction trial from 2.2 Gy to 2 Gy/fraction was conducted using modified planning target volume (PTV) contouring.

Image-guided interstitial high-dose-rate brachytherapy for locally recurrent uterine cervical cancer: A single-institution study.

The aim of this study was to investigate the efficacy and safety of image-guided high-dose-rate (HDR) interstitial brachytherapy (ISBT) for reirradiation of locally recurrent uterine cervical cancer.

Angiogenesis and VEGF-expressing cells are identified predominantly in the fascia rather than in the muscle during the early phase of dermatomyositis.

We previously demonstrated that fasciitis is a common lesion in dermatomyositis (DM) and that DM-associated fasciitis is detectable, as the result of the increased vascularity in the fascia, by power Doppler ultrasonography. We aimed to investigate whether angiogenesis and vascular endothelial growth factor (VEGF)-expressing cells in the fascia are histologically demonstrated during the early phase of DM, and whether inflammation is involved in angiogenesis and an increased number of VEGF-expressing cells.

Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP.

Brachytherapy for Buccal Cancer: From Conventional Low Dose Rate (LDR) or Mold Technique to High Dose Rate Interstitial Brachytherapy (HDR-ISBT).

To examine the effectiveness of newly-installed high-dose-rate interstitial brachytherapy (HDR-ISBT) for buccal cancer.


Interfractional Rectal Displacement Requiring Repeated Precaution Did Not Correlate to Biochemical Control and Rectal Toxicity in Patients with Prostate Cancer Treated with Image-guided Intensity-modulated Radiation Therapy.

To investigate the correlation between frequency of action level of interfractional rectal displacement requiring repeated precaution in patients with prostate cancer and late toxicity from image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy.

Tacrolimus-induced hypertrophic cardiomyopathy in a patient with dermatomyositis.

Identification of deleterious rare variants in MTTP, PNPLA3, and TM6SF2 in Japanese males and association studies with NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive fat deposits in hepatocytes without excessive alcohol intake. NAFLD is influenced by genetic factors, and the heritability has been estimated at 0.35 to 0.6 by twin studies. We explored rare variants in known NAFLD-associated genes to investigate whether these rare variants are involved in the susceptibility to NAFLD.

Measurement of exhaled nitric oxide and serum surfactant protein D levels for monitoring radiation pneumonitis following thoracic radiotherapy.

The present study aimed to examine the role of exhaled nitric oxide (eNO) and serum surfactant protein D (SP-D) level in the determination of radiation pneumonitis (RP) after thoracic radiotherapy (RT). The study included 34 treatments for 33 patients, including 16 three-dimensional conformal and 18 stereotactic body RT treatments. eNO levels were measured prior to RT, immediately subsequent to RT, every week during the RT course and at 1, 3, 6, 9 and 12 months following the treatment. The therapy reduced the eNO from 24.3±12.8 ppb prior to RT to 19.0±10.4 ppb immediately subsequent to RT (P=0.04). A total of 5 patients (14%) developed symptomatic RP of grade 2 or higher 3-5 months later, and exhibited an eNO elevation of 2.1±0.68-fold the minimum value, whereas the RP- group exhibited 1.4±0.6-fold elevation (P=0.02). The sensitivity of a cut-off of a 1.4-fold increase in the eNO ratio at the onset of RP was 100%; however, the specificity was 52%, and no predictive alterations to eNO levels were observed prior to the onset of RP. RT was associated with an elevated serum SP-D level at 3-6 months after RT. There was a statistically significant difference in the initial serum SP-D level between RP+ and RP- patients. In conclusion, obtaining the eNO ratio was a useful RP monitoring tool but did not predict RP occurrence in the present setting, whereas serum SP-D level may be a potential predictor for the detection of RP risk.

Radiotherapy for laryngeal cancer-technical aspects and alternate fractionation.

Early laryngeal, especially glottic, cancer is a good candidate for radiotherapy because obvious early symptoms (e.g. hoarseness) make earlier treatment possible and with highly successful localized control. This type of cancer is also a good model for exploring the basic principles of radiation oncology and several key findings (e.g. dose, fractionation, field size, patient fixation, and overall treatment time) have been noted. For example, unintended poor outcomes have been reported during transition from 60Cobalt to linear accelerator installation in the 1960s, with usage of higher energy photons causing poor dose distribution. In addition, shell fixation made precise dose delivery possible, but simultaneously elevated toxicity if a larger treatment field was necessary. Of particular interest to the radiation therapy community was altered fractionation gain as a way to improve local tumor control and survival rate. Unfortunately, this interest ceased with advancements in chemotherapeutic agents because alternate fractionation could not improve outcomes in chemoradiotherapy settings. At present, no form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy. In addition, the substantial workload associated with this technique made it difficult to add extra fractionation routinely in busy clinical hospitals. Hypofractionation, on the other hand, uses a larger single fractionation dose (2-3 Gy), making it a reasonable and attractive option for T1-T2 early glottic cancer because it can improve local control without the additional workload. Recently, Japan Clinical Oncology Group study 0701 reprised its role in early T1-T2 glottic cancer research, demonstrating that this strategy could be an optional standard therapy. Herein, we review radiotherapy history from 60Cobalt to modern linear accelerator, with special focus on the role of alternate fractionation.

Effect on gene expression of three allelic variants in GATA motifs of ABO, RHD, and RHCE regulatory elements.

Only a few genetic variants have been reported in regulatory elements of blood group genes. Most of them affect GATA motifs, binding sites for the GATA-1 transcription factor.

Effect of intratumoral abscess/necrosis on the outcome for head and neck cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife®.

The aim of the present study was to elucidate the effect of intratumoral abscess/necrosis (AN) on the outcome of patients with recurrent head and neck cancer (HNC) treated by stereotactic radiotherapy. The records of 67 patients treated with CyberKnife® in four institutes between August 2000 and July 2010 were reviewed. The frequency of AN appeared to be increased in younger postoperative patients with large ulcerative tumors. The AN+ group exhibited a better initial response rate compared with the AN- group (64 vs. 33%, respectively; P=0.04). The 1-year local control rate was 51 and 75% in the AN+ and AN- groups, respectively (P=0.01), while the respective 1-year overall survival rates were 53 and and 71% (P=0.0004). A total of 21 patients (31%) experienced grade ≥3 toxicities, and carotid blowout syndrome (CBOS) was found in 11 patients, resulting in 8 deaths. A significantly larger proportion of patients in the AN+ group developed CBOS (8/18; 44%) compared with the AN- group (3/49; 6%) (P=0.001). Therefore, AN may be an important prognostic factor for patients with recurrent HNC, as well as a predictor of lethal toxicity due to CBOS.

Uncertainty of cosmetic evaluation after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here.

Reirradiation for recurrent head and neck cancers using charged particle or photon radiotherapy.

To examine the outcomes of reirradiation for recurrent head and neck cancers using different modalities.

Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases.

We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer.

In Regard to Phan et al.

Comment on "Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer" Kari Tanderup et al.

Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients.

Myalgia in Patients with Dermatomyositis and Polymyositis Is Attributable to Fasciitis Rather Than Myositis: A Retrospective Study of 32 Patients who Underwent Histopathological Examinations.

To determine the association between fasciitis and the clinical variables in patients with dermatomyositis (DM) and polymyositis (PM).

Septic arthritis caused by Mycobacterium marinum infection.

Recommendations for high-risk clinical target volume definition with computed tomography for three-dimensional image-guided brachytherapy in cervical cancer patients.

Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial-caudal, lateral, or anterior-posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning.

Comparison of Re-irradiation Outcomes for Charged Particle Radiotherapy and Robotic Stereotactic Radiotherapy Using CyberKnife for Recurrent Head and Neck Cancers: A Multi-institutional Matched-cohort Analysis.

To compare survival outcomes for charged particle radiotherapy (CP) and stereotactic body radiotherapy using CyberKnife (CK) in patients who had undergone re-irradiation for head and neck cancers.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: clinical results with a median follow-up of 26 months.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months.

Salvage high-dose-rate brachytherapy for isolated vaginal recurrence of endometrial cancer.

We have retrospectively analyzed the outcomes of high-dose-rate (HDR) brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer.

Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis.

Prokineticin 2 (PK2) expression is upregulated in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. The purpose of our study was to investigate the effects of PK2 inhibition on CIA.

Brief Report: Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia: A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis.

We previously demonstrated that fasciitis is a common lesion of dermatomyositis (DM) that is detectable early after disease onset by en bloc muscle biopsy combined with magnetic resonance imaging (MRI). Power Doppler ultrasonography (PDUS) is a useful method for detection of inflammation and vascularity in rheumatic diseases. We undertook this study to determine whether fasciitis was detectable by PDUS in patients with DM.

Reirradiation using robotic image-guided stereotactic radiotherapy of recurrent head and neck cancer.

The purpose of this study was to examine the prognosis for patients with head and neck cancer after reirradiation using Cyberknife stereotactic body irradiation with special focus on mucosal ulceration. We conducted a retrospective multi-institutional review of 107 patients with previously irradiated head and neck cancer. The median follow-up time for all patients was 15 months, and the 2-year overall survival rate was 35%. Significant prognostic factors for overall survival were primary site (nasopharynx versus other sites), presence of ulceration, and PTV volume. Detailed analysis of ulceration showed a lower response rate (28%) in the ulceration (+) group than the ulceration (-) group (63%; P = 0.0045). The 2-year overall survival rates were 8% in the ulceration (+) group and 42.7% (P = 0.0001) in the ulceration (-) group, respectively. We recorded 22 severe toxicities, including 11 patients with carotid blow-out syndrome (CBOS), which was fatal in 9 patients. CBOS occurred in 6 patients with ulceration (6/25; 24%), and 5 patients experienced CBOS without ulceration (5/82; 6%; P=0.027). In conclusion, ulceration is an important prognostic factor, not only for adverse events but also for survival after reirradiation using CyberKnife.

Treatment Results of Radiotherapy Combined with Balloon-occluded Arterial Infusion Chemotherapy for Invasive Bladder Cancer.

We present preliminary results from our clinical study evaluating the effectiveness of combination of radiotherapy with balloon-occluded arterial infusion (BOAI) and hemodialysis (HD) for bladder cancer.

Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves: A hybrid computational approach.

Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves.