研究者詳細 - 藤原　智洋

論文 - 藤原　智洋

分割表示 200 件中 101 - 120 件目／全件表示 >>

【骨・軟部腫瘍のマネジメント(その1)】診断組織・遺伝子診断肉腫におけるがんゲノム医療の意義

中田英二, 藤原智洋, 国定俊之, 尾崎敏文, 遠西大輔, 冨田秀太, 平沢晃, 二川摩周, 武田達明

別冊整形外科 ( 79 ) 75 - 83 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめにがんにはさまざまな遺伝子異常を認め,同一のがん種でも発現する遺伝子が異なることが少なくない.最近,次世代シークエンサー(next generation sequencer:NGS)を用いて遺伝子異常を同時多重性(マルチプレックス)に検出するがん遺伝子パネルが登場した.がんゲノム医療では,がん遺伝子パネルで同定した遺伝子変異に基づいて薬剤を選択する,精密医療(precision medicine)が行われる.本稿では,肉腫におけるゲノム医療の意義について述べる.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600016&doc_link_id=10.15106%2Fj_besei79_75&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_75&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【骨・軟部腫瘍のマネジメント(その1)】治療総論免疫療法肉腫における免疫療法

中田英二, 藤原智洋, たき平将太, 国定俊之, 尾崎敏文

別冊整形外科 ( 79 ) 149 - 157 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめに肉腫における免疫療法の歴史は古く,1891年,William Coley博士は切除不能で転移性の肉腫の患者において免疫療法の効果を最初に示した.その後,免疫調節薬,ワクチンなどさまざまな免疫療法が開発され,最近は免疫チェックポイント阻害薬(immune-check point inhibitor:ICI)や活性化自己リンパ球輸注療法などの有望な治療法が登場している(表1).本稿では肉腫の免疫療法についてレビューを行う.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600029&doc_link_id=10.15106%2Fj_besei79_149&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_149&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Limb-salvage reconstruction following resection of pelvic bone sarcomas involving the acetabulum. 国際誌

Tomohiro Fujiwara, Manuel Ricardo Medellin Rincon, Andrea Sambri, Yusuke Tsuda, Rhys Clark, Jonathan Stevenson, Michael C Parry, Robert J Grimer, Lee Jeys

The bone & joint journal 103-B ( 4 ) 795 - 803 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Limb salvage for pelvic sarcomas involving the acetabulum is a major surgical challenge. There remains no consensus about what is the optimum type of reconstruction after resection of the tumour. The aim of this study was to evaluate the surgical outcomes in these patients according to the methods of periacetabular reconstruction. METHODS: The study involved a consecutive series of 122 patients with a periacetabular bone sarcoma who underwent limb-salvage surgery involving a custom-made prosthesis in 65 (53%), an ice-cream cone prosthesis in 21 (17%), an extracorporeal irradiated autograft in 18 (15%), and nonskeletal reconstruction in 18 (15%). RESULTS: The rates of major complications necessitating further surgery were 62%, 24%, 56%, and 17% for custom-made prostheses, ice-cream cone prostheses, irradiated autografts and nonskeletal reconstructions, respectively (p = 0.001). The ten-year cumulative incidence of failure of the reconstruction was 19%, 9%, 33%, and 0%, respectively. The major cause of failure was deep infection (11%), followed by local recurrence (6%). The mean functional Musculoskeletal Tumour Society (MSTS) scores were 59%, 74%, 64%, and 72%, respectively. The scores were significantly lower in patients with major complications than in those without complications (mean 52% (SD 20%) vs 74% (SD 19%); p < 0.001). For periacetabular resections involving the ilium, the mean score was the highest with custom-made prostheses (82% (SD 10%)) in patients without any major complication; however, nonskeletal reconstruction resulted in the highest mean scores (78% (SD 12%)) in patients who had major complications. For periacetabular resections not involving the ilium, significantly higher mean scores were obtained with ice-cream cone prostheses (79% (SD 17%); p = 0.031). CONCLUSION: Functional outcome following periacetabular reconstruction is closely associated with the occurrence of complications requiring further surgery. For tumours treated with periacetabular and iliac resection, skeletal reconstruction may result in the best outcomes in the absence of complications, whereas nonskeletal reconstruction is a reasonable option if the risk of complications is high. For tumours requiring periacetabular resection without the ilium, reconstruction using an ice-cream cone prosthesis supported by antibiotic-laden cement is a reliable option. Cite this article: Bone Joint J 2021;103-B(4):795-803.

DOI： 10.1302/0301-620X.103B4.BJJ-2020-0665.R1

【骨・軟部腫瘍のマネジメント(その1)】診断組織・遺伝子診断骨・軟部腫瘍におけるリキッドバイオプシーの開発

藤原智洋, 中田英二, 国定俊之, 尾崎敏文

別冊整形外科 ( 79 ) 63 - 69 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめに-リキッドバイオプシーとはリキッドバイオプシーとは,血液,尿,唾液などの体液中に含まれる細胞,核酸,蛋白質,代謝物などの生体分子の解析から病態の把握をめざす病態診断技術の総称である.この用語は,2010年代に血液中に存在する循環腫瘍細胞(circulating tumor cells:CTC)の検出による診断法に与えられたものであり,その後,核酸,蛋白質,代謝物などのさまざまな生体分子を対象とした解析法に対しても用いられるようになっている.現在では,循環腫瘍DNA(circulating tumor DNA:ctDNA),疾患特異的なマイクロRNA(microRNA:miRNA)などの核酸分子や,癌細胞由来のエクソソームの検出による疾患診断法の開発が精力的にすすめられている(図1).リキッドバイオプシーは非侵襲的かつ簡便に施行することができ,同一症例に対して繰り返し施行することが可能であるため,診断だけでなく治療効果や予後の予測に有用であり,次世代の診断技術の基盤として期待が集まっている.骨・軟部腫瘍には,消化器癌,前立腺癌,婦人科癌などの存在診断,治療効果予測,再発リスクの予測,術後再発のモニタリングなどに用いられる血液腫瘍マーカーがきわめて少ない.2012年の『軟部腫瘍診療ガイドライン』では,「臨床検査値で異常を示す腫瘍は?」というクリニカルクエスチョンに対して「軟部腫瘍で特異的な腫瘍マーカーは一般的にはない」と記載されている.癌腫と同様に乳酸脱水素酵素(LDH)の上昇を認めることがあるが,一般的には腫瘍サイズの大きな高悪性度軟部肉腫,あるいは多発性に転移して進行した軟部肉腫に限られる.このような背景から,肉腫細胞由来の生体分子を用いたリキッドバイオプシーの開発は,骨・軟部腫瘍の診療における新しいブレイクスルーとなる可能性があり,研究開発が精力的に行われている.本稿では,リキッドバイオプシーの骨・軟部腫瘍における研究開発の動向を生体分子別に述べ,本法の将来展望について論じる.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600014&doc_link_id=10.15106%2Fj_besei79_63&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_63&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Role of Tumor-Associated Macrophages in Sarcomas. 国際誌

Tomohiro Fujiwara, John Healey, Koichi Ogura, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Miho Kure, Hiroshi Tazawa, Eiji Nakata, Toshiyuki Kunisada, Toshiyoshi Fujiwara, Toshifumi Ozaki

Cancers 13 ( 5 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

DOI： 10.3390/cancers13051086

【希少がん-がん診療の新たな課題-】希少がん疾患各論骨軟部腫瘍・肉腫骨肉腫

国定俊之, 中田英二, 藤原智洋, 尾崎敏文

日本臨床 79 ( 増刊1 希少がん ) 454 - 461 2021年3月

Impact of NICE guidelines on the survival of patients with soft-tissue sarcomas. 国際誌

Tomohiro Fujiwara, Robert J Grimer, Scott Evans, Manuel Ricardo Medellin Rincon, Yusuke Tsuda, Louis-Romée Le Nail, Seggy Abudu

The bone & joint journal 103-B ( 3 ) 569 - 577 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Urgent referral to a specialist centre for patients with a soft-tissue sarcoma (STS) has been recommended by the National Institute for Health and Care Excellence (NICE) in the UK since 2006. However, the impact of this recommendation on the prognosis for these patients remains unclear. We aimed to determine the impact of the NICE guidelines on the disease-specific survival (DSS) of patients with an STS. METHODS: A total of 2,427 patients with an STS referred to a supraregional centre in the ten-year periods before (n = 1,386) and after (n = 1,041) the issue of the NICE guidelines were evaluated. RESULTS: The mean size of the tumour was significantly smaller at the time of diagnosis (10.3 cm (SD 6.5) vs 9.1 cm (SD 6.2); p < 0.001) and the number of patients who had undergone an inadvertent excision significantly decreased (28% (n = 389) vs 20% (n = 204); p < 0.001) following the introduction of the NICE guidelines. The five-year DSS was 63% in the pre-NICE and 71% in post-NICE groups (p < 0.001). The improved survival was more significant for those with a high-grade tumour (pre-NICE, 48%; post-NICE, 68%; p < 0.001). In those with a high-grade tumour, the mean size of the tumour (11.6 cm (SD 6.2) vs 9.6 cm (SD 5.8); p < 0.001) and the number of patients with metastasis at the time of diagnosis (15% (n = 124 vs 10% (n = 80); p = 0.007) significantly decreased in the post-NICE group. CONCLUSION: An improvement in survival was seen after the introduction of the NICE guidelines, especially in patients with a high-grade STS. More patients were referred at an earlier stage, indicating a clearer pathway after the issue of national policy for the management of STSs in the UK. Cite this article: Bone Joint J 2021;103-B(3):569-577.

DOI： 10.1302/0301-620X.103B3.BJJ-2020-0743.R1

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma? 国際誌

Kim M Tsoi, Martin Lowe, Yusuke Tsuda, Johnathan R Lex, Tomohiro Fujiwara, Ghassan Almeer, Jonathan Gregory, Jonathan Stevenson, Scott E Evans, Rajesh Botchu, Lee M Jeys

Clinical orthopaedics and related research 479 ( 2 ) 298 - 308 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules. QUESTIONS/PURPOSES: (1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN? METHODS: Between 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses. RESULTS: Following re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival. CONCLUSION: The findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed. LEVEL OF EVIDENCE: Level III, prognostic study.

DOI： 10.1097/CORR.0000000000001491

Interlocking reconstruction-mode stem-sideplates preserve at-risk hips with short residual proximal femora. 国際誌

Alexander B Christ, Tomohiro Fujiwara, Mohamed A Yakoub, John H Healey

The bone & joint journal 103-B ( 2 ) 398 - 404 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: We have evaluated the survivorship, outcomes, and failures of an interlocking, reconstruction-mode stem-sideplate implant used to preserve the native hip joint and achieve proximal fixation when there is little residual femur during large endoprosthetic reconstruction of the distal femur. METHODS: A total of 14 patients underwent primary or revision reconstruction of a large femoral defect with a short remaining proximal femur using an interlocking, reconstruction-mode stem-sideplate for fixation after oncological distal femoral and diaphyseal resections. The implant was attached to a standard endoprosthetic reconstruction system. The implant was attached to a standard endoprosthetic reconstruction system. None of the femoral revisions were amenable to standard cemented or uncemented stem fixation. Patient and disease characteristics, surgical history, final ambulatory status, and Musculoskeletal Tumor Society (MSTS) score were recorded. The percentage of proximal femur remaining was calculated from follow-up radiographs. RESULTS: All 14 at-risk native hip joints were preserved at a mean final follow-up of 6.0 years (SD 3.7), despite a short residual femur, often after proximal osteotomies through the lesser trochanter. Overall, 13 of 14 stems had long-term successful fixation. Eight patients required no reoperation. Three patients required reoperation due to implant-related issues, and three patients required reoperation for wound healing problems or infection. There were no dislocations or fractures. At final follow-up the mean MSTS score was 24.9 (SD 4.1). Nine patients required no ambulation aids, and only one had a Trendelenburg gait. CONCLUSION: This interlocking, reconstruction-mode stem-sideplate reliably preserves native hip joint anatomy and function after large femoral resection with a short remaining proximal femur, both in the primary and revision setting. This is particularly important for preventing or delaying total femoral arthroplasty in young patients after oncological reconstruction. Hip abductor strength and function could be maintained by this method, and the risk of dislocation eliminated. The success of this technique in this modest series should be verified in a larger collaborative study and will be of interest to revision surgeons and oncologists. Cite this article: Bone Joint J 2021;103-B(2):398-404.

DOI： 10.1302/0301-620X.103B2.BJJ-2020-0654.R1

The adequacy of resection margin for non-infiltrative soft-tissue sarcomas. 国際誌

Tomohiro Fujiwara, Jonathan Stevenson, Michael Parry, Yusuke Tsuda, Yoichi Kaneuchi, Lee Jeys

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47 ( 2 ) 429 - 435 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: There remains no consensus on what constitutes an adequate margin of resection for non-infiltrative soft-tissue sarcomas (STSs). We aimed to investigate the role of resection margins in millimetres for non-infiltrative STSs. METHODS: 502 patients who underwent surgical resection for a localized, non-infiltrative, high-grade STSs were studied. The prognostic significance of margin width was analysed and compared with the conventional R- and R+1-classification of surgical margins. RESULTS: The overall local recurrence (LR) rate was 13%; 9% and 27% with negative and positive margins, respectively (p < 0.001). In patients with negative margins, the LR rates were greater than 10% in patients with margins ≤5.0 mm but reduced to less than 4% with margins >5.0 mm. When classified by the R- (or R+1)-classification, the 5-year cumulative LR incidence was 8%, 23% (16%), and 31% for R0, R1, and R2, respectively, which did not stratify the LR risk with negative margins. On the other hand, an accurate risk stratification was possible by metric distance; the 5-year cumulative incidence of LR was 29%, 10%, and 1% with 0 mm, 0.1-5.0 mm, and >5.0 mm, respectively (p < 0.001). This classification also stratified the LR risk in patients with or without adjuvant radiotherapy. CONCLUSION: While a negative margin is essential to optimize local control in patients with non-infiltrative STSs, surgical margin width greater than 5 mm minimises the risk of local failure regardless of the use of adjuvant radiotherapy.

DOI： 10.1016/j.ejso.2020.06.020

Navigation-assisted pelvic resections and reconstructions for periacetabular chondrosarcomas. 国際誌

Tomohiro Fujiwara, Yoichi Kaneuchi, Jonathan Stevenson, Michael Parry, Vineet Kurisunkal, Rhys Clark, Yusuke Tsuda, Minna Laitinen, Robert Grimer, Lee Jeys

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47 ( 2 ) 416 - 423 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Survival in patients with chondrosarcomas has not improved over 40 years. Although emerging evidence has documented the efficacy of navigation-assisted surgery, the prognostic significance in chondrosarcomas remains unknown. We aimed to assess the clinical benefit of navigation-assisted surgery for pelvic chondrosarcomas involving the peri-acetabulum. METHODS: We studied 50 patients who underwent limb-sparing surgery for periacetabular chondrosarcomas performed with navigation (n = 13) without it (n = 37) at a referral musculoskeletal oncology centre between 2000 and 2015. RESULTS: The intralesional resection rates in the navigated and non-navigated groups were 8% (n = 1) and 19% (n = 7), respectively; all bone resection margins were clear in the navigated group. The 5-year cumulative incidence of local recurrence was 23% and 56% in the navigated and non-navigated groups, respectively (p = 0.035). There were no intra-operative complications related to use of navigation. There was a trend toward better functional outcomes in the navigated group (mean MSTS score, 67%) than the non-navigated group (mean MSTS score, 60%; p = 0.412). At a mean follow-up of 63 months, the 5-year disease-specific survival was 76% and 53% in the navigated and non-navigated group, respectively (p = 0.085), whilst the 5-year progression-free survival was 62% and 28% in the navigated and non-navigated group, respectively (p = 0.032). CONCLUSION: This study confirmed improved local control and progression-free survival with the use of computer navigation in patients with limb-salvage surgery for periacetabular chondrosarcomas, although the advancement in other treatment modalities is required for improvement of disease-specific survival.

DOI： 10.1016/j.ejso.2020.05.025

Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas. 国際誌

Meredith K Bartelstein, Divya Yerramilli, Alexander B Christ, Shachar Kenan, Koichi Ogura, Tomohiro Fujiwara, Nicola Fabbri, John H Healey

Sarcoma 2021 8877567 - 8877567 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Soft tissue sarcoma (STS) of the extremities is typically treated with limb-sparing surgery and radiation therapy; with this treatment approach, high local control rates can be achieved. However, postradiation bone fractures, fractures occurring in the prior radiation field with minimal or no trauma, are a serious late complication that occurs in 2-22% of patients who receive surgery and radiation for STS. Multiple risk factors for sustaining a postradiation fracture exist, including high radiation dose, female sex, periosteal stripping, older age, femur location, and chemotherapy administration. The treatment of these pathological fractures can be difficult, with complications including delayed union, nonunion, and infection posing particular challenges. Here, we review the mechanisms, risk factors, and treatment challenges associated with postradiation fractures in STS patients.

DOI： 10.1155/2021/8877567

Myxofibrosarcoma: Clinical and Prognostic Value of MRI Features. 国際誌

Paolo Spinnato, Andrea Sambri, Tomohiro Fujiwara, Luca Ceccarelli, Roberta Clinca, Manuel R Medellin, Massimiliano De Paolis, Davide M Donati, Giuseppe Bianchi

Current medical imaging 17 ( 2 ) 217 - 224 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Myxofibrosarcoma is one of the most common soft tissue sarcomas in the elderly. It is characterized by an extremely high rate of local recurrence, higher than other soft tissue tumors, and a relatively low risk of distant metastases.Magnetic resonance imaging (MRI) is the imaging modality of choice for the assessment of myxofibrosarcoma, which plays a key role in the preoperative setting of these patients. MRI features associated with the high risk of local recurrence are: high myxoid matrix content (water-like appearance of the lesions), high grade of contrast enhancement and presence of an infiltrative pattern ("tail sign"). On the other hand, MRI features associated with worse sarcoma specific survival are: large size of the lesion, deep location, high grade of contrast enhancement. Recognizing the above-mentioned imaging features of myxofibrosarcoma may be helpful in stratifying the risk for local recurrence and disease-specific survival. Moreover, the surgical planning should be adjusted according to the MRI features.

DOI： 10.2174/1573405616999200729152135

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. 国際誌

Toshinori Omori, Hiroshi Tazawa, Yasuaki Yamakawa, Shuhei Osaki, Joe Hasei, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

PloS one 16 ( 4 ) e0250643 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

DOI： 10.1371/journal.pone.0250643

Greater travel distance to specialized facilities is associated with higher survival for patients with soft-tissue sarcoma: US nationwide patterns. 国際誌

Tomohiro Fujiwara, Koichi Ogura, John Healey

PloS one 16 ( 6 ) e0252381 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The survival impact of geographic access to specialized care remains unknown in patients with soft-tissue sarcomas (STS). This study aimed to clarify the association between the patient travel distance and survival outcome and investigate the factors lying behind it. METHODS: A total of 34 528 patients with STS registered in the National Cancer Data Base, diagnosed from 2004-2016, were investigated. RESULTS: Tumor stage correlated with travel distance: patients with metastatic disease stayed closer to home. However, the type of facility showed greatest variation: 37.0%, 51.0%, 73.5%, and 75.9% of patients with ≤10 miles, 10.1-50 miles, 50.1-100 miles, and >100 miles, respectively (P<0.001), had a sarcoma care at academic/research centers. On a multivariable analysis, reduced mortality risk was associated with longer (versus short) travel distance (>100 miles: HR = 0.877; P = 0.001) and management at academic/research (versus non-academic/research) centers (HR = 0.857; P<0.001). The greatest divergence was seen in patients traveling very long distance (>100 miles) to an academic/research center, with a 26.9% survival benefit (HR = 0.731; P<0.001), compared with those traveling short distance (≤10 miles; 95.4% living in metropolitan area) to a non-academic/research center. There was no significant correlation between travel distance and survival in patients who had care at academic/research centers, whereas a survival benefit of management at academic/research centers was observed in every group of travel distance, regardless of tumor stage. CONCLUSIONS: This national study demonstrated that increased travel distance was associated with superior survival, attributable to a higher proportion of patients receiving sarcoma care at distant academic/research centers. These data support centralized care for STS. Overcoming referral and travel barriers may enable more patients to be treated at specialized centers and may further improve survival rates for patients with STS, even when it imposes an increased travel burden.

DOI： 10.1371/journal.pone.0252381

Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors. 国際誌

Toshiyuki Kunisada, Joe Hasei, Tomohiro Fujiwara, Eiji Nakata, Suguru Yokoo, Koji Demiya, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 21578 - 21578 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

DOI： 10.1038/s41598-020-78409-9

Development and external validation of nomograms to predict sarcoma-specific death and disease progression after surgical resection of localized high-grade conventional primary central chondrosarcoma and dedifferentiated chondrosarcoma. 国際誌

Yusuke Tsuda, Kim Tsoi, Jonathan D Stevenson, Minna Laitinen, Peter C Ferguson, Jay S Wunder, Anthony M Griffin, Michiel A J van de Sande, Veroniek van Praag, Andreas Leithner, Tomohiro Fujiwara, Hideo Yasunaga, Hiroki Matsui, Michael C Parry, Lee M Jeys

The bone & joint journal 102-B ( 12 ) 1752 - 1759 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Our aim was to develop and validate nomograms that would predict the cumulative incidence of sarcoma-specific death (CISSD) and disease progression (CIDP) in patients with localized high-grade primary central and dedifferentiated chondrosarcoma. METHODS: The study population consisted of 391 patients from two international sarcoma centres (development cohort) who had undergone definitive surgery for a localized high-grade (histological grade II or III) conventional primary central chondrosarcoma or dedifferentiated chondrosarcoma. Disease progression captured the first event of either metastasis or local recurrence. An independent cohort of 221 patients from three additional hospitals was used for external validation. Two nomograms were internally and externally validated for discrimination (c-index) and calibration plot. RESULTS: In the development cohort, the CISSD at ten years was 32.9% (95% confidence interval (CI) 19.8% to 38.4%). Age at diagnosis, grade, and surgical margin were found to have significant effects on CISSD and CIDP in multivariate analyses. Maximum tumour diameter was also significantly associated with CISSD. In the development cohort, the c-indices for CISSD and CIDP at five years were 0.743 (95% CI 0.700 to 0.819) and 0.761 (95% CI 0.713 to 0.800), respectively. When applied to the validation cohort, the c-indices for CISSD and CIDP at five years were 0.839 (95% CI 0.763 to 0.916) and 0.749 (95% CI 0.672 to 0.825), respectively. The calibration plots for these two nomograms demonstrated good fit. CONCLUSION: Our nomograms performed well on internal and external validation and can be used to predict CISSD and CIDP after resection of localized high-grade conventional primary central and dedifferentiated chondrosarcomas. They provide a new tool with which clinicians can assess and advise individual patients about their prognosis. Cite this article: Bone Joint J 2020;102-B(12):1752-1759.

DOI： 10.1302/0301-620X.102B12.BJJ-2020-0810.R1

Low-grade soft-tissue sarcomas: What is an adequate margin for local disease control? 国際誌

Tomohiro Fujiwara, Yoichi Kaneuchi, Yusuke Tsuda, Jonathan Stevenson, Michael Parry, Lee Jeys

Surgical oncology 35 303 - 308 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Whilst the resection margin is an established factor predictive of local control of soft-tissue sarcomas (STSs), the adequacy of margin width for low-grade STSs has been rarely described. We aimed to investigate the margin adequacy and its prognostic relevance in low-grade STSs. METHODS: 109 patients who underwent surgical treatment for a low-grade STS were studied. The prognostic value of margin status was evaluated according to the R-, R+1-classification, and width in millimetres. RESULTS: The 10-year local recurrence (LR) rates were 6%, 27%, 54% in R0, R1, and R2, respectively (p < 0.001), according to the R-classification. The R+1-classification resulted in a decreased LR rate in R1, but no major differences in LR rates in R0 and R2; 7%, 14%, 54% in R0, R1, and R2, respectively (p < 0.001). When classified by metric distance, 10-year LR rates were 0%, 8%, and 38% by ≥ 2.0 mm, 0.1-1.9 mm, and 0 mm margins, respectively (p < 0.001). Patients with close margins (0.1-1.9 mm) who received adjuvant radiotherapy had a trend toward lower LR risk than those without radiotherapy (10-year, 4% vs. 12%; p = 0.406). The 5 and 10-year disease-specific mortality was 9% and 13%, respectively; margin width was not associated with disease-specific mortality but LR was a poor prognostic factor for survival (p = 0.003). CONCLUSION: Whilst negative margin provided local control over 90%, excellent local control was achieved with microscopic margins ≥2 mm. The role of margins is more important than radiotherapy in local control. Margins do not determine survival, but LR is associated with a poor prognosis.

DOI： 10.1016/j.suronc.2020.08.022

What Are the Minimum Clinically Important Differences in SF-36 Scores in Patients with Orthopaedic Oncologic Conditions? 国際誌

Koichi Ogura, Mohamed A Yakoub, Alexander B Christ, Tomohiro Fujiwara, Zarko Nikolic, Patrick J Boland, John H Healey

Clinical orthopaedics and related research 478 ( 9 ) 2148 - 2158 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The SF-36 is widely used to evaluate the health-related quality of life of patients with musculoskeletal tumors. The minimum clinically important difference (MCID) is useful for interpreting changes in functional scores because it defines the smallest change each patient may perceive. Since the MCID is influenced by the population characteristics, MCIDs of the SF-36 should be defined to reflect the specific conditions of orthopaedic oncology patients. QUESTIONS/PURPOSES: (1) What is the MCID of SF-36 physical component summary (PCS) and mental component summary (MCS) scores in patients with orthopaedic oncologic conditions when calculated with distribution-based methods? (2) What is the MCID of SF-36 PCS and MCS scores in patients with orthopaedic oncologic conditions when calculated by anchor-based methods? METHODS: Of all 960 patients who underwent surgery from 1999 to 2005, 32% (310) of patients who underwent musculoskeletal oncologic surgery and completed two surveys during postoperative follow-up were reviewed. We evaluated a dataset that ended in 2005, completing follow-up of data accrued as part of the cooperative effort between the American Academy of Orthopaedic Surgeons and the Council of Musculoskeletal Specialty Societies to create patient reported quality of life instruments for lower extremity conditions. This effort, started in 1994 was validated and widely accepted by its publication in 2004. We believe the findings from this period are still relevant today because (1) this critical information has never been available for clinicians and researchers to distinguish real differences in outcome among orthopaedic oncology patients, (2) the SF-36 continues to be the best validated and widely used instrument to assess health-related quality of life, and unfortunately (3) there has been no significant change in outcome for oncology patients over the intervening years. SF-36 PCS and MCS are aggregates of the eight scale scores specific to physical and mental dimension (scores range from 0 to 100, with higher scores representing better health). Their responsiveness has been shown postoperatively for several surgical procedures (such as, colorectal surgery). Two different methods were used to calculate the MCID: the distribution-based method, which was based on half the SD of the change in score and standard error of the measurement at baseline, and anchor-based, in which a receiver operating characteristic (ROC) curve analysis was performed. The anchor-based method uses a plain-language question to ask patients how their individual conditions changed when compared with the previous survey. Answer choices were "much better," "somewhat better," "about the same," "somewhat worse," or "much worse." The ROC curve-derived MCIDs were defined as the change in scores from baseline, with sensitivity and specificity to detect differences in patients who stated their outcome was, about the same and those who stated their status was somewhat better or somewhat worse. This approach is based on each patient's perception. It considers that the definition of MCID is the minimal difference each patient can perceive as meaningful. RESULTS: Using the distribution-based method, we found that the MCIDs of the PCS and MCS were 5 and 5 by half the SD, and 6 and 5 by standard error of the measurement. In the anchor-based method, the MCIDs of the PCS and MCS for improvement/deterioration were 4 (area under the curve, 0.82)/-2 (area under the curve, 0.79) and 4 (area under the curve, 0.72)/ (area under the curve, 0.68), respectively. CONCLUSIONS: Since both anchor-based and distribution-based MCID estimates of the SF-36 in patients with musculoskeletal tumors were so similar, we have confidence in the estimates we made, which were about 5 points for both the PCS and the MCS subscales of the SF-36. This suggests that interventions improving SF-36 by less than that amount are unlikely to be perceived by patients as clinically important. Therefore, those interventions may not justify exposing patients to risk, cost, or inconvenience. When applying new interventions to orthopaedic oncology patients going forward, it will be important to consider these MCIDs for evaluation purposes. LEVEL OF EVIDENCE: Level III, diagnostic study.

DOI： 10.1097/CORR.0000000000001341

Chondrosarcoma of bone in children and adolescents. 国際誌

Yoichi Kaneuchi, Tomohiro Fujiwara, Yusuke Tsuda, Shinichirou Yoshida, Jonathan D Stevenson, Adesegun Abudu

Journal of children's orthopaedics 14 ( 4 ) 330 - 334 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: Chondrosarcomas typically present in adults during the fifth to seventh decades and are rare in young patients. The biological behaviour and oncological outcomes may be different in children and adolescents. Methods: We retrospectively evaluated the outcomes of all patients with chondrosarcoma of bone who were younger than 18 years of age at the time of diagnosis and were treated at our centre between 1995 and 2018. Results: The 15 consecutive patients studied included nine male and six female cases, with a mean age at diagnosis of 13 years (7 to 17). The median follow-up was 117 months (30 to 277). The tumours were primary and secondary in ten and five patients, respectively. The tumours were central in 13 and surface in two patients. The tumour locations were the humerus in five, digits in five, femur in three, radius in one and pelvis in one patient. The histological grades were grade I in seven, grade II in seven and grade III in one patient. The surgical treatments were limb salvage in ten patients and ray amputation in five patients. The surgical margins were wide in eight, marginal in two and intralesional in five patients. All the patients were alive and continuously free of disease at the time of the last follow-up. No patient developed metastases or local recurrence. Conclusion: Chondrosarcoma of bone in children and adolescent patients has a very good prognosis and is less aggressive compared with published outcomes in older patients. Level of evidence: IV.

DOI： 10.1302/1863-2548.14.200046

　前のページ - 次のページ　

1
2
3
4
5
6
7
8
9
10