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Satoaki Nakamura - 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.

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.

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.

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.

Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

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 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.

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.

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.

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.

Re-irradiation for locoregionally recurrent tumors of the thorax: a single-institution, retrospective study.

Re-irradiation (re-RT) of the thorax is challenging due to the impact of prior therapies on normal tissues, and there are few reports of definitive re-RT. The treatment toxicities and efficacy of re-RT are not well known. The aim of the present study was to assess the safety and efficacy of definitive re-RT of the thorax.

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.

Chemoradiotherapy for pancreatic cancer.

Superiority of charged particle therapy in treatment of hepatocellular carcinoma (Regarding Qi W.X. et al. charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: A systematic review and meta-analysis).

Predictive value of skin invasion in recurrent head and neck cancer patients treated by hypofractionated stereotactic re-irradiation using a cyberknife.

This study aimed to elucidate the influence of skin invasion in patients with recurrent head and neck cancer treated with re-irradiation using stereotactic radiotherapy.

Hypofractionated Radiotherapy for Localized Prostate Cancer: A Challenging Accelerated Hypofractionated Radiotherapy.

Conventionally fractionated (CF) external-beam radiation therapy (1.8-2.0 Gy/fraction) is an established treatment modality for localized prostate cancer. Emerging evidence suggests that the α/β ratio for prostate cancer is as low as 1.5, which has prompted investigators to explore hypofractionated (HF) radiation therapy. We reviewed the current status of hypofractionation and found that the accumulated outcomes reveal that dose escalation by moderate (2.5-4 Gy/fraction) hypofractionation (mHF) results in a better early biochemical outcome with acceptable complication rates, although there exist no marked advantages, other than the convenience of short treatment periods. Recently, hypofractionated external-beam radiotherapy has been challenged by accelerated hypofractionation (AHF), i.e., stereotactic body irradiation, particle therapy, and a high-dose-rate brachytherapy, using 5-10 Gy/fraction with a precise dose distribution and shorter treatment periods. Five-year biochemical control rates improved to >90%, even for high-risk groups, with a higher dose delivery using a safer technology. The overall survival rate reached nearly 100% at 5 years and was unaffected by prostate cancer, particularly in patients aged >80 years. Therefore, if maintaining the quality of life is the main purpose, short-term treatment is an attractive option from the socioeconomic perspective. Furthermore, CF and mHF regimens use equivalent doses at 2 Gy per fraction (EQD2) of 62-84 Gy, whereas AHF uses a higher EQD2 of 85 to 135 Gy if an α/β ratio of 1.5 is applied. In the preliminary phase, AHF has theoretical advantages that not only reduce the treatment period but also potentially improve BC, particularly in high-risk groups using a higher EQD2.

Validity of image-defined risk factors in localized neuroblastoma: A report from two centers in Western Japan.

Japanese Neuroblastoma Study Group (JNBSG) has been employing image-defined risk factors (IDRFs) since 2010. However, the report from INRG in 2011 supplemented description stating that isolated contact is considered to be IDRF-positive only in renal vessels. The aim of this study was to evaluate the validity of IDRFs by comparing the previous (PG) and new guidelines (NG).

Role of vaginal pallor reaction in predicting late vaginal stenosis after high-dose-rate brachytherapy in treatment-naive patients with cervical cancer.

To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy.

Preoperative chemoradiation for pancreatic cancer.

In regard to Brink et al.

Carotid blowout syndrome in pharyngeal cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife: A multi-institutional matched-cohort analysis.

Although reirradiation has attracted attention as a potential therapy for recurrent head and neck tumors with the advent of modern radiotherapy, severe rate toxicity such as carotid blowout syndrome (CBOS) limits its potential. The aim of this study was to identify the risk factors of CBOS after hypofractionated stereotactic radiotherapy (SBRT).

In regard to Morganti et al.

Analysis of intrafractional organ motion by megavoltage computed tomography in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy.

To analyze intrafractional organ motion in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy (SBRT-HT).

Frequency and predisposing factors for interfractional rectal displacement requiring repeated precaution in prostate cancer patients treated with image-guided intensity-modulated radiation therapy.

To investigate the frequency and characteristics of interfractional rectal displacement in patients with prostate cancer treated with image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy.

Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume.

To evaluate the role of hypofractionated stereotactic radiotherapy (hSRT) as a boost treatment for head and neck cancer.

Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis.

With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment.

Predisposing factors for larynx preservation strategies with non-surgical multimodality treatment for locally advanced (T3-4) larynx, hypopharynx and cervical esophageal disease.

To identify predisposing factors for larynx preservation strategies using non-surgical multimodality approaches.

Longitudinal analysis of late vaginal mucosal reactions after high-dose-rate brachytherapy in patients with gynecological cancer.

To longitudinally examine the late vaginal mucosal reactions in patients following high-dose-rate brachytherapy (BT).

Role of novel risk classification method, Prostate Cancer Risk Index (PRIX) for clinically localized prostate cancer after high-dose-rate interstitial brachytherapy as monotherapy.

To examine the role of the new grading system Prostate Cancer Risk Index (PRIX) with existing risk-grouping after high-dose-rate interstitial brachytherapy (HDR-ISBT) as monotherapy for localized prostate cancer.