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Koichi Yasuda

Bio: Koichi Yasuda is an academic researcher from Hokkaido University. The author has contributed to research in topics: Chemoradiotherapy & Medicine. The author has an hindex of 10, co-authored 51 publications receiving 564 citations.


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Journal ArticleDOI
TL;DR: The values for 18F-FMISO PET uptake and hypoxic volume in head and neck tumors between the 2 18F -FMISO scans were highly reproducible, which is promising for accurate radiation planning.
Abstract: Tumor hypoxia is well known to be radiation resistant. 18F-fluoromisonidazole (18F-FMISO) PET has been used for noninvasive evaluation of hypoxia. Quantitative evaluation of 18F-FMISO uptake is thus expected to play an important role in the planning of dose escalation radiotherapy. However, the reproducibility of 18F-FMISO uptake has remained unclarified. We therefore investigated the reproducibility of tumor hypoxia by using quantitative analysis of 18F-FMISO uptake. Methods: Eleven patients with untreated head and neck cancer underwent 2 18F-FMISO PET/CT scans (18F-FMISO1 and 18F-FMISO2) with a 48-h interval prospectively. All images were acquired at 4 h after 18F-FMISO injection for 10 min. The maximum standardized uptake (SUVmax), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of 18F-FMISO uptake were statistically compared between the 2 18F-FMISO scans by use of intraclass correlation coefficients (ICCs). The hypoxic volume was calculated as the area with a TBR of greater than or equal to 1.5 or the area with a TMR of greater than or equal to 1.25 to assess differences in hypoxic volume between the 2 18F-FMISO scans. The distances from the maximum uptake locations of the 18F-FMISO1 images to those of the 18F-FMISO2 images were measured to evaluate the locations of 18F-FMISO uptake. Results: The SUVmax (mean ± SD) for 18F-FMISO1 and 18F-FMISO2 was 3.16 ± 1.29 and 3.02 ± 1.12, respectively, with the difference between the 2 scans being 7.0% ± 4.6%. The TBRs for 18F-FMISO1 and 18F-FMISO2 were 2.98 ± 0.83 and 2.97 ± 0.64, respectively, with a difference of 9.9% ± 3.3%. The TMRs for 18F-FMISO1 and 18F-FMISO2 were 2.25 ± 0.71 and 2.19 ± 0.67, respectively, with a difference of 7.1% ± 5.3%. The ICCs for SUVmax, TBR, and TMR were 0.959, 0.913, and 0.965, respectively. The difference in hypoxic volume based on TBR was 1.8 ± 1.8 mL, and the difference in hypoxic volume based on TMR was 0.9 ± 1.3 mL, with ICCs of 0.986 and 0.996, respectively. The maximum uptake locations of the 18F-FMISO1 images were different from those of the 18F-FMISO2 images and were within the full width at half maximum of the PET/CT scanner, except in 1 case. Conclusion: The values for 18F-FMISO PET uptake and hypoxic volume in head and neck tumors between the 2 18F-FMISO scans were highly reproducible. Such high reproducibility of tumor hypoxia is promising for accurate radiation planning.

130 citations

Journal ArticleDOI
TL;DR: This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required.
Abstract: Objective: The most common chemoradiotherapy regimen is high-dose (100 mg/m 2 ) threeweekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. Methods: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m 2 ) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. Results: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m 2 cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). Conclusions: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly highdose cisplatin with concomitant radiotherapy.

77 citations

Journal ArticleDOI
TL;DR: In this article, the authors investigated the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN).
Abstract: Purpose The purpose of this study was to elucidate the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN). Methods and Materials Sixty-seven patients (43 male and 24 female) diagnosed with EMPHN between 1983 and 2008 at 23 Japanese institutions were reviewed. The median patient age was 64 years (range, 12–83). The median dose administered was 50 Gy (range, 30–64 Gy). Survival data were calculated by the Kaplan-Meier method. Results The median follow-up duration was 63 months. Major tumor sites were nasal or paranasal cavities in 36 (54%) patients, oropharynx or nasopharynx in 16 (23%) patients, orbita in 6 (9%) patients, and larynx in 3 (5%) patients. The 5- and 10-year local control rates were 95% and 87%, whereas the 5- and 10-year disease-free survival rates were 56% and 54%, respectively. There were 5 (7.5%), 12 (18%), and 8 (12%) patients who experienced local failure, distant metastasis, and progression to multiple myeloma, respectively. In total, 18 patients died, including 10 (15%) patients who died due to complications from EMPHN. The 5- and 10-year overall survival (OS) rates were 73% and 56%, respectively. Radiotherapy combined with surgery was identified as the lone significant prognostic factor for OS (p = 0.04), whereas age, gender, radiation dose, tumor size, and chemotherapy were not predictive. No patient experienced any severe acute morbidity. Conclusions Radiotherapy was quite effective and safe for patients with EMPHN. Radiotherapy combined with surgery produced a better outcome according to survival rates. These findings require confirmation by further studies with larger numbers of patients with EMPHN.

76 citations

Journal ArticleDOI
TL;DR: Excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT is shown, with acceptable rates of acute and late toxicity.
Abstract: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100–120 mg m−2 per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65–70 Gy). One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions. We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

50 citations

Journal ArticleDOI
TL;DR: In this article, the authors provide a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases for squamous cell carcinoma of the head and neck.
Abstract: Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.

32 citations


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Journal ArticleDOI
TL;DR: Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia.
Abstract: Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro-drugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia.

383 citations

Journal ArticleDOI
TL;DR: The assessment of tumor Hypoxia will be valuable to radiation oncologists, surgeons, and biotechnology and pharmaceutical companies who are engaged in developing hypoxia-based therapies or treatment strategies.
Abstract: Tumor hypoxia is a well-established biological phenomenon that affects the curability of solid tumors, regardless of treatment modality. Especially for head and neck cancer patients, tumor hypoxia is linked to poor patient outcomes. Given the biological problems associated with tumor hypoxia, the goal for clinicians has been to identify moderately to severely hypoxic tumors for differential treatment strategies. The “gold standard” for detecting and characterizing of tumor hypoxia are the invasive polarographic electrodes. Several less invasive hypoxia assessment techniques have also shown promise for hypoxia assessment. The widespread incorporation of hypoxia information in clinical tumor assessment is severely impeded by several factors, including regulatory hurdles and unclear correlation with potential treatment decisions. There is now an acute need for approved diagnostic technologies for determining the hypoxia status of cancer lesions, as it would enable clinical development of personalize...

307 citations

Journal ArticleDOI
TL;DR: This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently availablehypoxia radiotracers.
Abstract: Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.

272 citations

Journal ArticleDOI
TL;DR: Evaluated data exists to support a high level of evidence for the benefit of hypoxic modification, but such hypoxia modification still has no impact on general clinical practice.
Abstract: Since the initial observations made at the beginning of the last century, it has been established that solid tumors contain regions of low oxygenation (hypoxia). Tumor cells can survive in these hypoxic conditions and are a major factor in tumor radioresistance. This significance has resulted in hypoxia becoming the most cited biological topic in translational radiation oncology. Identifying hypoxic cells in human tumors has become paramount, and the ability to do this has been improved by the help of new imaging techniques and the use of predictive gene profiles. Substantial data confirm the presence of hypoxia in many types of human tumors, although with considerable heterogeneity among individual tumors. Various approaches have been investigated for eliminating the hypoxic population. These include increasing oxygen availability, directly radiosensitizing or killing the hypoxic cells, indirectly affecting them by targeting the tumor vascular supply, increasing the radiation dose to this resistant population, or by using radiation with a high linear energy transfer, for which hypoxia is believed to be less of an issue. Many of these approaches have undergone controlled clinical trials during the last 50 years, and the results have shown that hypoxic radiation resistance can indeed be overcome. Thus, ample data exists to support a high level of evidence for the benefit of hypoxic modification. However, such hypoxic modification still has no impact on general clinical practice. In this review we summarize the biological rationale, and the current activities and trials, related to identifying and overcoming hypoxia in modern radiotherapy.

219 citations

Journal ArticleDOI
01 Jan 2008
TL;DR: In this paper, the authors evaluated clinical factors that are associated with and might predict severe late toxicity after concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN).
Abstract: Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 p...

207 citations