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Accuracy of Time to Treatment Initiation Data in Musculoskeletal Soft Tissue Sarcoma. 肌肉骨骼软组织肉瘤开始治疗时间的准确性。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1155/2023/9022770
Joshua M Lawrenz, Jose F Vega, Jaiben George, Gannon L Curtis, Jaymeson Gordon, Amanda Maggiotto, Katherine Tullio, Dale R Shepard, John D Reith, Herbert S Schwartz, Lukas M Nystrom, Nathan W Mesko

Background: Time to treatment initiation (TTI) is a quality metric in cancer care. The purpose of this study is to determine the accuracy of TTI data from a single cancer center registry that reports to the National Cancer Database (NCDB) for sarcoma diagnoses.

Methods: A retrospective analysis of a single Commission on Cancer (CoC)-accredited cancer center's tumor registry between 2006 and 2016 identified 402 patients who underwent treatment of a musculoskeletal soft tissue sarcoma and had TTI data available. Registry-reported TTI was extracted from the tumor registry. Effective TTI was manually calculated by medical record review as the number of days from the date of tissue diagnosis to initiation of first effective treatment. Effective treatment was defined as oncologic surgical excision or initiation of radiation therapy or chemotherapy. Registry-reported TTI and effective TTI values were compared for concordance in all patients.

Results: In the entire cohort, 25% (99/402) of patients had TTI data discordance, all related to surgical treatment definition. For patients with a registry-reported value of TTI = 0 days, 74% (87/118) had a diagnostic surgical procedure coded as their first treatment event, with 73 unplanned incomplete excision procedures and 14 incisional biopsies. In these patients, effective TTI was on average 59 days (P < 0.001). For patients with a registry-reported value of TTI >0 days, only 4% (12/284) had discordant TTI values.

Conclusions: Nearly three-fourths of patients with a registry-reported value of TTI = 0 days in a large, CoC-accredited cancer center registry had a diagnostic procedure coded as their first treatment event, though their effective treatment had not yet started. These data suggest that TTI is likely longer than what is reported to the NCDB. Redefinition of what constitutes surgical treatment should be considered to improve the accuracy of data used in measuring TTI in sarcoma.

背景:治疗起始时间(TTI)是癌症治疗的质量指标。本研究的目的是确定来自单一癌症中心登记处的TTI数据的准确性,该登记处向国家癌症数据库(NCDB)报告肉瘤诊断。方法:对2006年至2016年单个癌症委员会(CoC)认可的癌症中心的肿瘤登记进行回顾性分析,确定了402例接受肌肉骨骼软组织肉瘤治疗并具有TTI数据的患者。登记报告的TTI是从肿瘤登记中提取的。有效TTI是通过病历审查手动计算的,即从组织诊断之日到开始第一次有效治疗的天数。有效的治疗被定义为肿瘤手术切除或开始放射治疗或化疗。比较所有患者登记报告的TTI值和有效TTI值的一致性。结果:在整个队列中,25%(99/402)的患者TTI数据不一致,均与手术治疗定义有关。对于登记报告的TTI值为0天的患者,74%(87/118)的诊断性手术被编码为他们的第一次治疗事件,73例非计划的不完全切除手术和14例切口活检。在这些患者中,有效TTI平均为59天(P < 0.001)。对于登记报告的TTI值>0天的患者,只有4%(12/284)的TTI值不一致。结论:在coc认可的大型癌症中心登记处,近四分之三的登记报告TTI值为0天的患者将诊断程序编码为他们的第一次治疗事件,尽管他们的有效治疗尚未开始。这些数据表明,TTI可能比报告给国家开发银行的时间更长。应该考虑重新定义什么是手术治疗,以提高用于测量肉瘤TTI数据的准确性。
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引用次数: 0
Postoperative Complication and Reoperation Rates Following Resection of Soft Tissue vs. Bone Malignancies Based on Anatomic Location in the Inpatient Setting. 基于住院患者解剖位置的软组织与骨恶性肿瘤切除术术后并发症和再手术率。
Q2 Medicine Pub Date : 2023-01-01 DOI: 10.1155/2023/5455719
Alexander M Ballatori, Shane Shahrestani, Andy Ton, Xiao T Chen, Tarek Yamout, Brandon S Gettleman, Nathanael D Heckmann, Lawrence R Menendez, Alexander B Christ

Introduction: Surgical excisions of upper and lower extremity malignancies are increasing annually, due in part to the rising incidence of sarcomas. The purpose of this study is to compare readmissions, reoperation rate, and complications following surgical excision of soft/connective tissue vs bone malignancies of the upper and lower extremities.

Methods: The Nationwide Readmissions Database (NRD) was queried from 2016-2017 to conduct a retrospective analysis of 16,435 patients diagnosed with malignant neoplasms of the long bone (ULLB, n = 1,433) and soft tissue (ULST, n = 2,049) of the upper limb and malignant neoplasms of the long bone (LLLB, n = 5,422) and soft tissue (LLST, n = 7,531) of the lower limb. Patients who underwent surgical excision of their neoplasms were included. Binomial multivariate logistic regression was used to compare complications, nonelective readmission rates, and reoperation rates between the two groups at 30 and 90 days.

Results: Average age of the ULST group was 61.88, with 36% female. Average age of the ULLB group was 44.97, with 41.90% female. Average age of the LLST group was 60.96, with 46.90% female. Average age of the LLLB group was 43.09, with 42.60% female. The ULST group had lower odds of readmission within 30 days (p=0.263), which became significant within 90 days of surgery (p=0.045). The LLST group had significantly higher odds of infection, reoperation within 30 to 90 days of the index surgery compared to the LLLB group (p < 0.0001). The LLST group had significantly lower odds of readmission within 30 (p=0.04) and 90 days (p=0.015) of the index surgery.

Conclusion: Patients in the ULST group had significantly lower odds of 90-day readmission compared to the ULLB group. There were also significantly lower odds of 30- and 90-day readmission in the LLST group compared to the LLLB group. However, the LLST group had significantly higher odds of infection and reoperation within 30 and 90 days compared to the LLLB group.

导读:上肢和下肢恶性肿瘤的手术切除每年都在增加,部分原因是肉瘤发病率的上升。本研究的目的是比较软性/结缔组织与上肢和下肢骨恶性肿瘤手术切除后的再入院率、再手术率和并发症。方法:查询2016-2017年全国再入院数据库(NRD),对16435例诊断为上肢长骨恶性肿瘤(ULLB, n = 1433)、软组织恶性肿瘤(ULST, n = 2049)和下肢长骨恶性肿瘤(LLLB, n = 5422)、软组织恶性肿瘤(LLST, n = 7531)的患者进行回顾性分析。接受手术切除肿瘤的患者也包括在内。采用二项多因素logistic回归比较两组患者在30天和90天的并发症、非选择性再入院率和再手术率。结果:ULST组患者平均年龄61.88岁,女性占36%。ULLB组平均年龄44.97岁,女性占41.90%。LLST组平均年龄60.96岁,女性占46.90%。LLLB组平均年龄43.09岁,女性占42.60%。ULST组在30天内再入院的几率较低(p=0.263),这在90天内变得显著(p=0.045)。与LLLB组相比,LLST组在指数手术后30 ~ 90天内感染和再手术的几率显著高于LLLB组(p < 0.0001)。LLST组在指数手术后30天(p=0.04)和90天(p=0.015)内再入院的几率显著降低。结论:ULST组患者90天再入院率明显低于ULLB组。与LLLB组相比,LLST组30天和90天再入院的几率也显著降低。然而,与LLLB组相比,LLST组在30天和90天内感染和再手术的几率明显更高。
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引用次数: 0
Patient-Specific Instruments for Forearm Sarcoma Resection and Allograft Reconstruction in Children: Results in 4 Cases. 儿童前臂肉瘤切除和异体移植物重建的患者专用器械:4例结果。
Q2 Medicine Pub Date : 2022-10-31 eCollection Date: 2022-01-01 DOI: 10.1155/2022/7005629
Amaury Paulmier, Mathieu Raad, Charles-Edouard Verhelle, Laurent Paul, Pierre-Louis Docquier

For pediatric malignant bone tumors located in the limbs, limb salvage surgery is the gold standard, but it requires adequate resection margins to avoid local recurrence. Primitive bone sarcomas of the forearm (radius or ulna) are very rare and the reconstruction remains challenging. We describe a method to ensure minimal but adequate resection bone margins with precision in four consecutive patients with primitive bone sarcomas of the forearm. During the preoperative planning, magnetic resonance imaging (MRI) was used to delineate the tumor and the tumor volume was transferred to computerized tomography (CT) by image fusion. A patient-specific instrument (PSI) was manufactured by 3D printing to allow the surgeon to perform the surgical cuts precisely according to the preoperative planning. The first PSI was used for the resection of the tumor, which adopted a unique position at the bony surface. A second PSI was intended for the cutting of the bone allograft so that it fitted perfectly with the bone defect. In all four cases, the safe margin obtained into the bone was free of tumor (R0: microscopically margin-negative resection). The functional result was very good in all four patients. This limb salvage surgical technique can be applied in forearm bone sarcoma and improves surgical precision while maintaining satisfactory local tumor control. It can also reduce the surgical time and allow a stable osteosynthesis.

对于儿童四肢恶性骨肿瘤,保肢手术是金标准,但需要足够的切除边缘以避免局部复发。前臂(桡骨或尺骨)的原始骨肉瘤是非常罕见的,重建仍然具有挑战性。我们描述了一种方法,以确保最小的,但足够的切除骨边缘与精度在四个连续的患者原始骨肉瘤的前臂。在术前计划中,使用磁共振成像(MRI)描绘肿瘤,并通过图像融合将肿瘤体积转移到计算机断层扫描(CT)。患者专用仪器(PSI)通过3D打印制造,使外科医生能够根据术前计划精确地进行手术切割。第一次PSI用于切除肿瘤,它在骨表面采用了独特的位置。第二次PSI用于切割同种异体骨移植物,使其与骨缺损完美吻合。在所有四个病例中,进入骨的安全边缘均无肿瘤(R0:显微镜下边缘阴性切除)。所有4例患者的功能结果都非常好。该保肢手术技术可应用于前臂骨肉瘤,在保持良好的局部肿瘤控制的同时,提高手术精度。它还可以减少手术时间,使骨固定稳定。
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引用次数: 0
Risk of Malignant Transformation of Giant Cell Tumors of Bone Is 8 Times Lower with Megavoltage vs. Orthovoltage Radiation Therapy. 骨巨细胞瘤恶性转化的风险是正电压放疗的8倍。
Q2 Medicine Pub Date : 2022-10-21 eCollection Date: 2022-01-01 DOI: 10.1155/2022/7216296
Farah N Musharbash, Alexander Edelstein, Jad M El Abiad, Adam S Levin, Sara R Alcorn, Carol D Morris

Background: The first-line treatment for most giant cell tumors (GCTs) of bone is surgical; radiotherapy (RT) is reserved for inoperable or refractory cases. While RT techniques have undergone a dramatic change over the past few decades, with the higher energy megavoltage RT replacing orthovoltage RT, concerns for high rates of malignant transformation following RT have limited its use. Evidence suggests a lower incidence of secondary malignancy after treatment with megavoltage compared with orthovoltage RT, but this has not been studied in GCTs. Our main purpose was to compare the incidence of malignant transformation of GCTB between patients treated with orthovoltage vs. megavoltage RT.

Methods: A literature review was performed to identify studies reporting GCTBs treated with RT from 01/1900 through 12/2019. Studies that did not report RT modality or separate orthovoltage and megavoltage results were excluded. Included in the analysis were 6 patients from our institution. Primary outcome was the incidence of malignant transformation; secondary outcomes were time to transformation and incidence of local recurrence. Fisher's exact tests and independent sample t-tests were used, and significance was set at p < 0.05.

Results: Twenty-two studies were included, which reported on 168 GCTBs treated with orthovoltage and 393 treated with megavoltage RT. Transformation incidence was 14% (n = 24) for orthovoltage and 1.8% (n = 7) for megavoltage RT, an 8-fold difference (odds ratio (OR) 9.1, 95% confidence interval (CI) 3.9-22, p < 0.001). Mean time to transformation was 8.7 years for orthovoltage and 11.2 years for megavoltage RT (p=0.28). Incidence of local recurrence was 38% (63/167) for orthovoltage and 17% (66/393) for megavoltage RT (OR 3.3, 95% CI 2.0-4.6, p < 0.001).

Conclusions: The risk of developing a malignancy after RT of GCTB is 8 times lower with megavoltage than with orthovoltage. Malignant transformation with megavoltage, while not zero, is lower than that in historical series. Use of modern RT techniques in inoperable or refractory GCTB may be appropriate.

背景:骨巨细胞瘤(gct)的一线治疗是手术;放疗(RT)是为不能手术或难治性病例保留的。虽然RT技术在过去的几十年里发生了巨大的变化,随着能量更高的兆瓦电压RT取代了正电压RT,但对RT后高恶性转化率的担忧限制了它的使用。有证据表明,与正电压放疗相比,巨电压放疗后继发恶性肿瘤的发生率较低,但尚未在gct中进行研究。我们的主要目的是比较正压和特压放疗治疗的GCTB恶性转化的发生率。方法:回顾文献,确定1900年1月至2019年12月期间报道RT治疗GCTBs的研究。未报道RT模式或单独的正电压和巨电压结果的研究被排除。纳入分析的是我们机构的6例患者。主要观察指标为恶性转化的发生率;次要结果为转化时间和局部复发率。采用Fisher精确检验和独立样本t检验,显著性设为p < 0.05。结果:纳入了22项研究,其中正压治疗168例gctb和特大电压RT治疗393例。正压治疗的转化发生率为14% (n = 24),特大电压RT治疗的转化发生率为1.8% (n = 7),差异为8倍(优势比(OR) 9.1, 95%可信区间(CI) 3.9-22, p < 0.001)。正压转换平均时间为8.7年,特压转换平均时间为11.2年(p=0.28)。正电压组局部复发率为38%(63/167),高压组局部复发率为17% (66/393)(OR 3.3, 95% CI 2.0 ~ 4.6, p < 0.001)。结论:巨电压治疗GCTB术后发生恶性肿瘤的风险比正电压治疗低8倍。巨电压时的恶性转化虽不为零,但低于历史序列。在不能手术或难治性GCTB中使用现代放射治疗技术可能是合适的。
{"title":"Risk of Malignant Transformation of Giant Cell Tumors of Bone Is 8 Times Lower with Megavoltage vs. Orthovoltage Radiation Therapy.","authors":"Farah N Musharbash, Alexander Edelstein, Jad M El Abiad, Adam S Levin, Sara R Alcorn, Carol D Morris","doi":"10.1155/2022/7216296","DOIUrl":"10.1155/2022/7216296","url":null,"abstract":"<p><strong>Background: </strong>The first-line treatment for most giant cell tumors (GCTs) of bone is surgical; radiotherapy (RT) is reserved for inoperable or refractory cases. While RT techniques have undergone a dramatic change over the past few decades, with the higher energy megavoltage RT replacing orthovoltage RT, concerns for high rates of malignant transformation following RT have limited its use. Evidence suggests a lower incidence of secondary malignancy after treatment with megavoltage compared with orthovoltage RT, but this has not been studied in GCTs. Our main purpose was to compare the incidence of malignant transformation of GCTB between patients treated with orthovoltage vs. megavoltage RT.</p><p><strong>Methods: </strong>A literature review was performed to identify studies reporting GCTBs treated with RT from 01/1900 through 12/2019. Studies that did not report RT modality or separate orthovoltage and megavoltage results were excluded. Included in the analysis were 6 patients from our institution. Primary outcome was the incidence of malignant transformation; secondary outcomes were time to transformation and incidence of local recurrence. Fisher's exact tests and independent sample <i>t</i>-tests were used, and significance was set at <i>p</i> < 0.05.</p><p><strong>Results: </strong>Twenty-two studies were included, which reported on 168 GCTBs treated with orthovoltage and 393 treated with megavoltage RT. Transformation incidence was 14% (<i>n</i> = 24) for orthovoltage and 1.8% (<i>n</i> = 7) for megavoltage RT, an 8-fold difference (odds ratio (OR) 9.1, 95% confidence interval (CI) 3.9-22, <i>p</i> < 0.001). Mean time to transformation was 8.7 years for orthovoltage and 11.2 years for megavoltage RT (<i>p</i>=0.28). Incidence of local recurrence was 38% (63/167) for orthovoltage and 17% (66/393) for megavoltage RT (OR 3.3, 95% CI 2.0-4.6, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>The risk of developing a malignancy after RT of GCTB is 8 times lower with megavoltage than with orthovoltage. Malignant transformation with megavoltage, while not zero, is lower than that in historical series. Use of modern RT techniques in inoperable or refractory GCTB may be appropriate.</p>","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":" ","pages":"7216296"},"PeriodicalIF":0.0,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40656804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adjuvant Radiation after Primary Resection of Atypical Lipomatous Tumors of the Extremity Reduces Local Recurrence but Increases Complications: A Multicenter Evaluation. 肢体非典型脂肪瘤初次切除后的辅助放疗减少了局部复发,但增加了并发症:一项多中心评估。
Q2 Medicine Pub Date : 2022-08-22 eCollection Date: 2022-01-01 DOI: 10.1155/2022/2091677
Joshua M Lawrenz, Samuel R Johnson, Kevin Zhu, Mallory McKeon, Cullen P Moran, Jose Vega, Katherine S Hajdu, James P Norris, Leo Y Luo, Eric T Shinohara, Justin M M Cates, Brian P Rubin, John D Reith, Jennifer L Halpern, Nathan W Mesko, Herbert S Schwartz, Lukas M Nystrom, Ginger E Holt

Background: Radiation after resection of an atypical lipomatous tumor (ALT) is controversial. This study evaluates local control and complications after the first resection of ALTs of the extremity with or without adjuvant radiation.

Methods: A dual institution, retrospective review of patients treated from 1995 to 2020 with first-time resection of an ALT in the extremity was performed. In total, 102 patients underwent adjuvant radiation (XRT group) and 68 patients were treated with surgery alone (no-XRT group). The median follow-up time was 4.6 years (interquartile range (IQR) 2.0-7.3 years). The median radiation dose was 60 Gy (IQR 55-66 Gy). Univariable and multivariable analyses evaluated the association of patient, tumor, and treatment variables with recurrence and complications. Kaplan-Meier analysis evaluated local recurrence-free survival (LRFS) and time to complication.

Results: The overall incidence of local recurrence was 1% (1/102) in the XRT group and 24% (16/68) in the no-XRT group (p < 0.001). The median time-to-recurrence was 8.2 years (IQR 6.5-10.5 years). In the XRT and the no-XRT groups, 5-yr LRFS was 98% and 92% (p=0.21) and 10-yr LRFS was 98% and 41% (p < 0.001), respectively. The absence of radiation (HR = 23.63, 95% CI (3.09-180.48); p < 0.001) and R2 surgical resection margins (HR = 11.04, 95% CI (2.07-59.03); p < 0.001) incurred a 23-fold and 11-fold increased risk of local recurrence, respectively, while tumor size, depth, location, and neurovascular involvement were not found to be independent predictors of recurrence. The complication rate was 37% (38/102) in the XRT group and 10% (7/68) in the no-XRT group (p < 0.001). Eight patients (8/102, 8%) required surgical management for complication in the XRT group compared with two patients (2/68, 3%) in the no-XRT group (p=0.10). Higher radiation dose had a modest correlation with increased severity of complication (ρ=0.24; p=0.02).

Conclusions: Adjuvant radiation after first-time resection of an ALT of the extremity was associated with a significantly reduced risk of local recurrence but a three-fold increase in complication rate. These data support a 10-year follow-up for these patients and inform a notable clinical trade-off if considering adjuvant radiation for this tumor with recurrent potential.

背景:非典型脂肪瘤(ALT)切除术后的放疗是有争议的。本研究评估首次切除肢体ALTs后的局部控制和并发症,有或没有辅助放疗。方法:对1995年至2020年首次切除肢体ALT的双机构患者进行回顾性分析。102例患者接受辅助放疗(XRT组),68例患者单独接受手术治疗(无XRT组)。中位随访时间为4.6年(四分位间距(IQR) 2.0 ~ 7.3年)。中位辐射剂量为60 Gy (IQR 55 ~ 66 Gy)。单变量和多变量分析评估了患者、肿瘤和治疗变量与复发和并发症的关系。Kaplan-Meier分析评估局部无复发生存期(LRFS)和并发症发生时间。结果:XRT组总局部复发率为1%(1/102),未XRT组总局部复发率为24% (16/68)(p < 0.001)。中位复发时间为8.2年(IQR为6.5-10.5年)。在XRT组和非XRT组中,5年LRFS分别为98%和92% (p=0.21), 10年LRFS分别为98%和41% (p < 0.001)。无辐射(HR = 23.63, 95% CI (3.09-180.48);p < 0.001)和R2手术切除边缘(HR = 11.04, 95% CI (2.07-59.03);P < 0.001)分别增加了23倍和11倍的局部复发风险,而肿瘤大小、深度、位置和神经血管受累并不是复发的独立预测因素。XRT组并发症发生率为37%(38/102),无XRT组并发症发生率为10%(7/68),差异有统计学意义(p < 0.001)。XRT组有8例患者(8/ 102,8%)因并发症需要手术治疗,而非XRT组有2例患者(2/ 68,3%)(p=0.10)。较高的辐射剂量与并发症严重程度的增加有适度的相关性(ρ=0.24;p = 0.02)。结论:首次切除肢体ALT后的辅助放疗与局部复发风险显著降低相关,但并发症发生率增加三倍。这些数据支持对这些患者进行10年随访,并告知如果考虑对有复发潜力的肿瘤进行辅助放疗,需要进行显著的临床权衡。
{"title":"Adjuvant Radiation after Primary Resection of Atypical Lipomatous Tumors of the Extremity Reduces Local Recurrence but Increases Complications: A Multicenter Evaluation.","authors":"Joshua M Lawrenz,&nbsp;Samuel R Johnson,&nbsp;Kevin Zhu,&nbsp;Mallory McKeon,&nbsp;Cullen P Moran,&nbsp;Jose Vega,&nbsp;Katherine S Hajdu,&nbsp;James P Norris,&nbsp;Leo Y Luo,&nbsp;Eric T Shinohara,&nbsp;Justin M M Cates,&nbsp;Brian P Rubin,&nbsp;John D Reith,&nbsp;Jennifer L Halpern,&nbsp;Nathan W Mesko,&nbsp;Herbert S Schwartz,&nbsp;Lukas M Nystrom,&nbsp;Ginger E Holt","doi":"10.1155/2022/2091677","DOIUrl":"https://doi.org/10.1155/2022/2091677","url":null,"abstract":"<p><strong>Background: </strong>Radiation after resection of an atypical lipomatous tumor (ALT) is controversial. This study evaluates local control and complications after the first resection of ALTs of the extremity with or without adjuvant radiation.</p><p><strong>Methods: </strong>A dual institution, retrospective review of patients treated from 1995 to 2020 with first-time resection of an ALT in the extremity was performed. In total, 102 patients underwent adjuvant radiation (XRT group) and 68 patients were treated with surgery alone (no-XRT group). The median follow-up time was 4.6 years (interquartile range (IQR) 2.0-7.3 years). The median radiation dose was 60 Gy (IQR 55-66 Gy). Univariable and multivariable analyses evaluated the association of patient, tumor, and treatment variables with recurrence and complications. Kaplan-Meier analysis evaluated local recurrence-free survival (LRFS) and time to complication.</p><p><strong>Results: </strong>The overall incidence of local recurrence was 1% (1/102) in the XRT group and 24% (16/68) in the no-XRT group (<i>p</i> < 0.001). The median time-to-recurrence was 8.2 years (IQR 6.5-10.5 years). In the XRT and the no-XRT groups, 5-yr LRFS was 98% and 92% (<i>p</i>=0.21) and 10-yr LRFS was 98% and 41% (<i>p</i> < 0.001), respectively. The absence of radiation (HR = 23.63, 95% CI (3.09-180.48); <i>p</i> < 0.001) and R2 surgical resection margins (HR = 11.04, 95% CI (2.07-59.03); <i>p</i> < 0.001) incurred a 23-fold and 11-fold increased risk of local recurrence, respectively, while tumor size, depth, location, and neurovascular involvement were not found to be independent predictors of recurrence. The complication rate was 37% (38/102) in the XRT group and 10% (7/68) in the no-XRT group (<i>p</i> < 0.001). Eight patients (8/102, 8%) required surgical management for complication in the XRT group compared with two patients (2/68, 3%) in the no-XRT group (<i>p</i>=0.10). Higher radiation dose had a modest correlation with increased severity of complication (<i>ρ</i>=0.24; <i>p</i>=0.02).</p><p><strong>Conclusions: </strong>Adjuvant radiation after first-time resection of an ALT of the extremity was associated with a significantly reduced risk of local recurrence but a three-fold increase in complication rate. These data support a 10-year follow-up for these patients and inform a notable clinical trade-off if considering adjuvant radiation for this tumor with recurrent potential.</p>","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":" ","pages":"2091677"},"PeriodicalIF":0.0,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40335938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Malignant Transformation of Giant Cell Tumor of Bone and the Association with Denosumab Treatment: A Radiology and Pathology Perspective. 骨巨细胞瘤的恶性转化及其与Denosumab治疗的关系:放射学和病理学的观点。
Q2 Medicine Pub Date : 2022-06-17 eCollection Date: 2022-01-01 DOI: 10.1155/2022/3425221
K van Langevelde, A H G Cleven, A Navas Cañete, L van der Heijden, M A J van de Sande, H Gelderblom, J V M G Bovée

Objective: Malignancy in giant cell tumor of bone (mGCTB) is categorized as primary (concomitantly with conventional GCTB) or secondary (after radiotherapy or other treatment). Denosumab therapy has been suggested to play a role in the etiology of secondary mGCTB. In this case series from a tertiary referral sarcoma center, we aimed to find distinctive features for malignant transformation in GCTB on different imaging modalities. Furthermore, we assessed the duration of denosumab treatment and lag time to the development of malignancy.

Methods: From a histopathology database search, 6 patients were pathologically confirmed as having initial conventional GCTB and subsequently with secondary mGCTB.

Results: At the time of mGCTB diagnosis, 2 cases were treated with denosumab only, 2 with denosumab and surgery, 1 with multiple curettages and radiotherapy, and 1 with surgery only. In the 4 denosumab treated patients, the mean lag time to malignant transformation was 7 months (range 2-11 months). Imaging findings suspicious of malignant transformation related to denosumab therapy are the absence of fibro-osseous matrix formation and absent neocortex formation on CT, and stable or even increased size of the soft tissue component.

Conclusion: In 4 patients treated with denosumab, secondary mGCTB occurred within the first year after initiation of treatment. Radiotherapy-associated mGCTB has a longer lag time than denosumab-associated mGCTB. Close clinical and imaging follow-up during the first months of denosumab therapy is key, as mGCTB tends to have rapid aggressive behavior, similar to other high-grade sarcomas. Nonresponders should be (re) evaluated for their primary diagnosis of conventional GCTB.

目的:骨巨细胞瘤(mGCTB)的恶性分为原发性(合并常规巨细胞瘤)和继发性(经放疗或其他治疗后)。Denosumab治疗已被认为在继发性mGCTB的病因学中发挥作用。在这个来自三级转诊肉瘤中心的病例系列中,我们旨在发现不同成像方式下GCTB恶性转化的独特特征。此外,我们评估了地诺单抗治疗的持续时间和恶性肿瘤发展的滞后时间。方法:从组织病理学数据库检索,6例患者病理证实为最初的常规GCTB,随后继发性mGCTB。结果:mGCTB确诊时,单纯地诺单抗治疗2例,单纯地诺单抗联合手术治疗2例,多次刮痧联合放疗1例,单纯手术治疗1例。在4例denosumab治疗的患者中,到恶性转化的平均滞后时间为7个月(范围2-11个月)。影像学表现怀疑与denosumab治疗相关的恶性转化是CT上没有纤维骨基质形成和没有新皮质形成,软组织成分稳定甚至增大。结论:在4例接受denosumab治疗的患者中,继发性mGCTB在开始治疗后的一年内发生。放疗相关的mGCTB比denosumab相关的mGCTB有更长的延迟时间。在denosumab治疗的头几个月密切的临床和影像学随访是关键,因为mGCTB倾向于具有快速的侵袭行为,类似于其他高级别肉瘤。无应答者应(重新)评估其对常规GCTB的初步诊断。
{"title":"Malignant Transformation of Giant Cell Tumor of Bone and the Association with Denosumab Treatment: A Radiology and Pathology Perspective.","authors":"K van Langevelde,&nbsp;A H G Cleven,&nbsp;A Navas Cañete,&nbsp;L van der Heijden,&nbsp;M A J van de Sande,&nbsp;H Gelderblom,&nbsp;J V M G Bovée","doi":"10.1155/2022/3425221","DOIUrl":"https://doi.org/10.1155/2022/3425221","url":null,"abstract":"<p><strong>Objective: </strong>Malignancy in giant cell tumor of bone (mGCTB) is categorized as primary (concomitantly with conventional GCTB) or secondary (after radiotherapy or other treatment). Denosumab therapy has been suggested to play a role in the etiology of secondary mGCTB. In this case series from a tertiary referral sarcoma center, we aimed to find distinctive features for malignant transformation in GCTB on different imaging modalities. Furthermore, we assessed the duration of denosumab treatment and lag time to the development of malignancy.</p><p><strong>Methods: </strong>From a histopathology database search, 6 patients were pathologically confirmed as having initial conventional GCTB and subsequently with secondary mGCTB.</p><p><strong>Results: </strong>At the time of mGCTB diagnosis, 2 cases were treated with denosumab only, 2 with denosumab and surgery, 1 with multiple curettages and radiotherapy, and 1 with surgery only. In the 4 denosumab treated patients, the mean lag time to malignant transformation was 7 months (range 2-11 months). Imaging findings suspicious of malignant transformation related to denosumab therapy are the absence of fibro-osseous matrix formation and absent neocortex formation on CT, and stable or even increased size of the soft tissue component.</p><p><strong>Conclusion: </strong>In 4 patients treated with denosumab, secondary mGCTB occurred within the first year after initiation of treatment. Radiotherapy-associated mGCTB has a longer lag time than denosumab-associated mGCTB. Close clinical and imaging follow-up during the first months of denosumab therapy is key, as mGCTB tends to have rapid aggressive behavior, similar to other high-grade sarcomas. Nonresponders should be (re) evaluated for their primary diagnosis of conventional GCTB.</p>","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":" ","pages":"3425221"},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40509893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Oncological and Functional Outcomes after Hemicortical Resection and Biological Reconstruction Using Allograft for Parosteal Osteosarcoma of the Distal Femur 股骨远端骨旁骨肉瘤半皮质切除和同种异体骨移植生物重建后的肿瘤和功能结果
Q2 Medicine Pub Date : 2022-06-02 DOI: 10.1155/2022/5153924
O. Savvidou, Stavros D Goumenos, Ioannis G. Trikoupis, A. Kaspiris, Dimitra Melissaridou, P. Gavriil, J. Georgoulis, P. Papagelopoulos
Background Parosteal osteosarcoma (PAOS) is a surface osteosarcoma. Treatment options include wide excision and endoprosthetic or allograft. However, due to the low local recurrence and metastasis rate, when it appears in the posterior surface of the distal femur, the lesion can be managed with hemicortical wide resection and biological reconstruction with hemicortical allograft. The purpose of this study is to evaluate the oncological and functional outcomes of patients with parosteal osteosarcoma (PAOS) of the posterior cortex of the distal femur who underwent biological reconstruction after hemicortical resection. Methods Eleven patients who underwent wide tumor resection and defect reconstruction of the posterior surface of the distal femur using hemicortical allograft were retrospectively studied. Local recurrence, metastasis, complications, and the functional outcome using the Musculoskeletal Tumor Society (MSTS) scoring system were evaluated. Results The average postoperative follow-up period was 53.64 months (range, 30 to 84 months). At the latest follow-up, all patients had no evidence of disease without metastases. One patient with local recurrence underwent revision surgery with fibula autograft reconstruction. The mean MSTS score was 93.45 ± 3.56. Conclusions Treatment of patients with PAOS of the posterior aspect of the distal femur with hemicortical resection and allograft reconstruction has satisfactory oncological and functional outcome and low complication rates.
腮腺骨肉瘤(PAOS)是一种表面骨肉瘤。治疗选择包括广泛切除和内修复或同种异体移植物。然而,由于局部复发和转移率较低,当病变出现在股骨远端后表面时,可以通过半皮质广泛切除和半皮质同种异体移植物生物重建来治疗。本研究的目的是评估股骨远端后皮质骨旁骨肉瘤(PAOS)患者在半皮质切除后进行生物重建的肿瘤学和功能结果。方法回顾性分析11例应用半皮质同种异体骨移植行股骨远端大面积肿瘤切除和缺损重建的患者。使用肌肉骨骼肿瘤学会(MSTS)评分系统评估局部复发、转移、并发症和功能结果。结果术后平均随访时间为53.64个月(30~84个月) 月)。在最近的随访中,所有患者都没有出现无转移的疾病迹象。1例局部复发患者接受了自体腓骨移植重建的翻修手术。MSTS平均得分为93.45 ± 3.56.结论采用半皮质切除和同种异体移植物重建治疗股骨远端后部PAOS患者具有满意的肿瘤学和功能结果,并发症发生率低。
{"title":"Oncological and Functional Outcomes after Hemicortical Resection and Biological Reconstruction Using Allograft for Parosteal Osteosarcoma of the Distal Femur","authors":"O. Savvidou, Stavros D Goumenos, Ioannis G. Trikoupis, A. Kaspiris, Dimitra Melissaridou, P. Gavriil, J. Georgoulis, P. Papagelopoulos","doi":"10.1155/2022/5153924","DOIUrl":"https://doi.org/10.1155/2022/5153924","url":null,"abstract":"Background Parosteal osteosarcoma (PAOS) is a surface osteosarcoma. Treatment options include wide excision and endoprosthetic or allograft. However, due to the low local recurrence and metastasis rate, when it appears in the posterior surface of the distal femur, the lesion can be managed with hemicortical wide resection and biological reconstruction with hemicortical allograft. The purpose of this study is to evaluate the oncological and functional outcomes of patients with parosteal osteosarcoma (PAOS) of the posterior cortex of the distal femur who underwent biological reconstruction after hemicortical resection. Methods Eleven patients who underwent wide tumor resection and defect reconstruction of the posterior surface of the distal femur using hemicortical allograft were retrospectively studied. Local recurrence, metastasis, complications, and the functional outcome using the Musculoskeletal Tumor Society (MSTS) scoring system were evaluated. Results The average postoperative follow-up period was 53.64 months (range, 30 to 84 months). At the latest follow-up, all patients had no evidence of disease without metastases. One patient with local recurrence underwent revision surgery with fibula autograft reconstruction. The mean MSTS score was 93.45 ± 3.56. Conclusions Treatment of patients with PAOS of the posterior aspect of the distal femur with hemicortical resection and allograft reconstruction has satisfactory oncological and functional outcome and low complication rates.","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":"2022 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42890157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma FAK-Src复合物在促结缔组织增生小圆细胞瘤、尤文氏肉瘤和横纹肌肉瘤中的靶向作用
Q2 Medicine Pub Date : 2022-05-11 DOI: 10.1155/2022/3089424
A. V. van Erp, M. H. Hillebrandt-Roeffen, Niek van Bree, Tim A. Plüm, U. Flucke, I. Desar, E. Fleuren, W. V. D. van der Graaf, Y. Versleijen-Jonkers
Desmoplastic small round cell tumors (DSRCTs), Ewing sarcoma (ES), and alveolar and embryonal rhabdomyosarcoma (ARMS and ERMS) are malignant sarcomas typically occurring at young age, with a poor prognosis in the metastatic setting. New treatment options are necessary. Src family kinase inhibitor dasatinib single-agent treatment has been investigated in a phase 2 study in patients with advanced sarcomas including ES and RMS but failed as a single agent in these subtypes. Since previous studies demonstrated high FAK and Src activities in RMS and ES tissue and cell lines, and dasatinib treatment was shown to upregulate activated FAK, we hypothesized that FAK-Src combination treatment could potentially be an interesting treatment option for these tumor types. We examined the effects of targeting the FAK-Src complex by addressing (p)FAK and (p)Src expressions in tumor sections of DSRCT (n = 13), ES (n = 68), ARMS (n = 21), and ERMS (n = 39) and by determining the antitumor effects of single and combined treatment with FAK inhibitor defactinib and multikinase (Abl/SFK) inhibitor dasatinib in vitro on cell lines of each subtype. In vivo effects were assessed in DSRCT and ERMS models. Concurrent pFAK and pSrc expressions (H-score >50) were observed in DSRCT (67%), ES (6%), ARMS (35%), and ERMS (19%) samples. Defactinib treatment decreased pFAK expression and reduced cell viability in all subtypes. Dasatinib treatment decreased pSrc expression and cell viability in each subtype. Combination treatment led to a complete reduction in pFAK and pSrc in each cell line and showed enhanced cell viability reduction, drug synergy, DNA damage induction, and a trend toward higher apoptosis induction in DSRCT, ERMS, and ARMS but not in ES cells. These promising in vitro results unfortunately do not translate into promising in vivo results as we did not observe a significant effect on tumor volume in vivo, and the combination did not show superior effects compared to dasatinib single-agent treatment.
Desmoplastic小圆细胞瘤(DSRCTs)、尤因肉瘤(ES)、肺泡和胚胎性横纹肌肉瘤(ARMS和ERMS)是恶性肉瘤,通常发生在年轻时,在转移环境中预后较差。新的治疗方案是必要的。Src家族激酶抑制剂达沙替尼单剂治疗已在一项2期研究中对包括ES和RMS在内的晚期肉瘤患者进行了研究,但在这些亚型中作为单剂治疗失败。由于先前的研究表明RMS和ES组织和细胞系中的FAK和Src活性较高,并且达沙替尼治疗可上调活化的FAK,我们假设FAK-Src联合治疗可能是这些肿瘤类型的一种有趣的治疗选择。我们通过处理(p)FAK和(p)Src在DSRCT(n = 13) ,ES(n = 68),ARMS(n = 21)和ERMS(n = 39),并通过测定FAK抑制剂defactinib和多激酶(Abl/SFK)抑制剂达沙替尼在体外单独和联合治疗对每种亚型的细胞系的抗肿瘤作用。在DSRCT和ERMS模型中评估体内效应。在DSRCT(67%)、ES(6%)、ARMS(35%)和ERMS(19%)样本中观察到pFAK和pSrc同时表达(H-core>50)。Defactinib治疗降低了pFAK的表达,降低了所有亚型的细胞活力。达沙替尼治疗降低了每个亚型中pSrc的表达和细胞活力。联合治疗导致每个细胞系中pFAK和pSrc的完全减少,并在DSRCT、ERMS和ARMS中显示出增强的细胞活力降低、药物协同作用、DNA损伤诱导,以及更高的凋亡诱导趋势,但在ES细胞中没有。不幸的是,这些有希望的体外结果并没有转化为有希望的体内结果,因为我们没有观察到对体内肿瘤体积的显著影响,而且与达沙替尼单剂治疗相比,该组合也没有显示出优越的效果。
{"title":"Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma","authors":"A. V. van Erp, M. H. Hillebrandt-Roeffen, Niek van Bree, Tim A. Plüm, U. Flucke, I. Desar, E. Fleuren, W. V. D. van der Graaf, Y. Versleijen-Jonkers","doi":"10.1155/2022/3089424","DOIUrl":"https://doi.org/10.1155/2022/3089424","url":null,"abstract":"Desmoplastic small round cell tumors (DSRCTs), Ewing sarcoma (ES), and alveolar and embryonal rhabdomyosarcoma (ARMS and ERMS) are malignant sarcomas typically occurring at young age, with a poor prognosis in the metastatic setting. New treatment options are necessary. Src family kinase inhibitor dasatinib single-agent treatment has been investigated in a phase 2 study in patients with advanced sarcomas including ES and RMS but failed as a single agent in these subtypes. Since previous studies demonstrated high FAK and Src activities in RMS and ES tissue and cell lines, and dasatinib treatment was shown to upregulate activated FAK, we hypothesized that FAK-Src combination treatment could potentially be an interesting treatment option for these tumor types. We examined the effects of targeting the FAK-Src complex by addressing (p)FAK and (p)Src expressions in tumor sections of DSRCT (n = 13), ES (n = 68), ARMS (n = 21), and ERMS (n = 39) and by determining the antitumor effects of single and combined treatment with FAK inhibitor defactinib and multikinase (Abl/SFK) inhibitor dasatinib in vitro on cell lines of each subtype. In vivo effects were assessed in DSRCT and ERMS models. Concurrent pFAK and pSrc expressions (H-score >50) were observed in DSRCT (67%), ES (6%), ARMS (35%), and ERMS (19%) samples. Defactinib treatment decreased pFAK expression and reduced cell viability in all subtypes. Dasatinib treatment decreased pSrc expression and cell viability in each subtype. Combination treatment led to a complete reduction in pFAK and pSrc in each cell line and showed enhanced cell viability reduction, drug synergy, DNA damage induction, and a trend toward higher apoptosis induction in DSRCT, ERMS, and ARMS but not in ES cells. These promising in vitro results unfortunately do not translate into promising in vivo results as we did not observe a significant effect on tumor volume in vivo, and the combination did not show superior effects compared to dasatinib single-agent treatment.","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47607021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Free Vascularized Fibula Salvage of Failed CPH in Pediatric Sarcoma Patients 游离带血管腓骨修复小儿肉瘤CPH失败的疗效
Q2 Medicine Pub Date : 2022-05-09 DOI: 10.1155/2022/6240293
Giovanna R. Pires, Whitney D. Moss, Jessica Luo, Ruyan Zhang, Kevin B. Jones, A. Kwok, J. Agarwal
Background Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90–95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population. Methods Five patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded. Results Five patients (average age = 8.4 years; range = 5–10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma (n = 4) or Ewing sarcoma (n = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up. Conclusion Primary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.
背景由于预期寿命的延长和最近手术技术的改进,保肢已经取代截肢成为金标准,目前90%至95%的上肢恶性肿瘤都在进行保肢手术。然而,这些挽救性手术中的许多都与严重的术后并发症有关。特别是,肱骨前锁骨(CPH)手术与高骨不连发生率有关。我们介绍了在儿科人群中,在原始CPH手术失败或不愈合后,使用游离血管腓骨皮瓣(VFF)挽救上肢的经验。方法对5例18岁以下诊断为上肢肉瘤的患者进行了肿瘤切除并立即进行CPH重建并伴有骨不连,随后用游离VFF进行翻修。记录患者人口统计数据、肿瘤学特征、手术程序、术中细节、术后并发症和移植物愈合时间。结果5名患者(平均年龄 = 8.4年;范围 = 术后5-10年)在肱骨近端骨肉瘤CPH重建失败后,接受了二次保肢手术,并进行了游离VFF重建(n = 4) 或尤因肉瘤(n = 1) 。平均随访3.7年。并发症发生在5名患者中(100%),其中3名患者需要再次手术(60%)。4名患者实现移植物愈合(平均愈合时间 = 3.7个月)和成功的肢体重建。4名患者存活,无局部复发。一名患者没有达到愈合,失去了随访。结论儿童原发性骨肿瘤需要广泛的手术切除,重建往往并发症发生率高,需要进一步手术。在先前重建失败后,游离VFF是一种可行的上肢挽救选择,因为它为瘢痕组织床提供了血管化组织,并允许替换或扩大大型骨缺损。
{"title":"Free Vascularized Fibula Salvage of Failed CPH in Pediatric Sarcoma Patients","authors":"Giovanna R. Pires, Whitney D. Moss, Jessica Luo, Ruyan Zhang, Kevin B. Jones, A. Kwok, J. Agarwal","doi":"10.1155/2022/6240293","DOIUrl":"https://doi.org/10.1155/2022/6240293","url":null,"abstract":"Background Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90–95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population. Methods Five patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded. Results Five patients (average age = 8.4 years; range = 5–10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma (n = 4) or Ewing sarcoma (n = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up. Conclusion Primary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46173937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plexin-B2 and Semaphorins Do Not Drive Rhabdomyosarcoma Proliferation or Migration Plexin-B2和Semaphorins不驱动横纹肌肉瘤的增殖或迁移
Q2 Medicine Pub Date : 2022-05-06 DOI: 10.1155/2022/9646909
Anju Karki, R. Purohit, Sofia Nosack, N. Bharathy, J. Michalek, Sonja Chen, Charles Keller
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnosis will experience only 8% disease-free 5-year survival for nonlocalized unresectable recurrent disease. Hence, development of novel therapeutic strategies is urgently needed to improve outcomes. The Plexin-Semaphorin pathway is largely unexplored for sarcoma research. However, emerging interest in the Plexin-Semaphorin signaling axis in pediatric sarcomas has led to phase I cooperative group dose-finding clinical trials, now completed (NCT03320330). In this study, we specifically investigated the protein expression of transmembrane receptor Plexin-B2 and its cognate SEMA4C ligands in clinical RMS tumors and cell models. By RNA interferences, we assessed the role of Plexin-B2 in cell growth and cell migration ability in selected alveolar and embryonal RMS cell model systems. Our results affirmed expression of Plexin-B2 across human samples, while also dissecting expression of the different protein subunits of Plexin-B2 along with the assessment of preferred Semaphorin ligands of Plexin-B2. Plexin-B2 knockdown had positive or negative effects on cell growth, which varied by cell model system. Migration assayed after Plexin-B2 knockdown revealed selective cell line specific migration inhibition, which was independent of Plexin-B2 expression level. Overall, these findings are suggestive of context-specific and possibly patient-specific (stochastic) role of Plexin-B2 and SEMA4 ligands in RMS.
横纹肌肉瘤(RMS)是最常见的儿童软组织肉瘤,其患者亚群的临床需求长期未得到满足。例如,在诊断时患有肺泡横纹肌肉瘤和转移的儿童,对于非局部不可切除的复发性疾病,5年无病生存率仅为8%。因此,迫切需要开发新的治疗策略来改善疗效。Plexin Semaphorin通路在很大程度上未被用于肉瘤研究。然而,对儿童肉瘤中Plexin Semaphorin信号轴的新兴趣导致了I期合作组剂量发现临床试验,现已完成(NCT03320330)。在本研究中,我们专门研究了跨膜受体Plexin-B2及其同源SEMA4C配体在临床RMS肿瘤和细胞模型中的蛋白质表达。通过RNA干扰,我们评估了Plexin-B2在选定的肺泡和胚胎RMS细胞模型系统中的细胞生长和细胞迁移能力中的作用。我们的结果肯定了Plexin-B2在人类样本中的表达,同时也分析了Plexin-B2不同蛋白质亚基的表达,以及对Plexin-B2的优选Semaphorin配体的评估。Plexin-B2敲除对细胞生长有积极或消极的影响,这因细胞模型系统而异。Plexin-B2敲低后测定的迁移显示选择性细胞系特异性迁移抑制,这与Plexin-B1的表达水平无关。总的来说,这些发现提示了Plexin-B2和SEMA4配体在RMS中的环境特异性和可能的患者特异性(随机)作用。
{"title":"Plexin-B2 and Semaphorins Do Not Drive Rhabdomyosarcoma Proliferation or Migration","authors":"Anju Karki, R. Purohit, Sofia Nosack, N. Bharathy, J. Michalek, Sonja Chen, Charles Keller","doi":"10.1155/2022/9646909","DOIUrl":"https://doi.org/10.1155/2022/9646909","url":null,"abstract":"Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnosis will experience only 8% disease-free 5-year survival for nonlocalized unresectable recurrent disease. Hence, development of novel therapeutic strategies is urgently needed to improve outcomes. The Plexin-Semaphorin pathway is largely unexplored for sarcoma research. However, emerging interest in the Plexin-Semaphorin signaling axis in pediatric sarcomas has led to phase I cooperative group dose-finding clinical trials, now completed (NCT03320330). In this study, we specifically investigated the protein expression of transmembrane receptor Plexin-B2 and its cognate SEMA4C ligands in clinical RMS tumors and cell models. By RNA interferences, we assessed the role of Plexin-B2 in cell growth and cell migration ability in selected alveolar and embryonal RMS cell model systems. Our results affirmed expression of Plexin-B2 across human samples, while also dissecting expression of the different protein subunits of Plexin-B2 along with the assessment of preferred Semaphorin ligands of Plexin-B2. Plexin-B2 knockdown had positive or negative effects on cell growth, which varied by cell model system. Migration assayed after Plexin-B2 knockdown revealed selective cell line specific migration inhibition, which was independent of Plexin-B2 expression level. Overall, these findings are suggestive of context-specific and possibly patient-specific (stochastic) role of Plexin-B2 and SEMA4 ligands in RMS.","PeriodicalId":21431,"journal":{"name":"Sarcoma","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49072947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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Sarcoma
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