躯干和肢体软组织肉瘤的围手术期化疗与放疗（英文）
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摘要
虽然手术是肢体和躯干原发软组织肉瘤的根治性治疗手段,但对于高危患者单纯手术常难以获得疾病的长期控制。治疗失败的主要原因为远处转移,其次为局部复发。一些局部进展期的患者可能面临无法手术切除,或仅边缘可切除,因此预后很差。围手术期的系统治疗和放疗可提高手术疗效。如何确立围手术期系统治疗的价值颇具挑战。系统治疗可以缩小肿瘤。但要证明其对局部控制的价值从而促进实施更为保守的外科手术的证据仍不充分。对于那些原发肿瘤被认定为难以或不可能切除的患者,新辅助化疗可能为疾病的局部控制提供一种选择。围手术期的系统治疗也可以避免远处转移的发生。近期的研究表明,以蒽环类药物/异环磷酰胺为基础的辅助治疗能够使患者获益,虽然证据来自于对一项大型研究的再次分析。一项新辅助化疗的随机研究提示,对某些经过选择的肉瘤组织学亚型,以蒽环类药物/异环磷酰胺为基础的系统化疗可能改善患者无病生存和总生存期。其疗效的获得主要是通过改善远处无转移生存而不是局控率的提高。这两项研究所采用的方法均存在一定的局限性,因此需要进一步探索。尽管如此,我们相信这些结果支持在局部进展期、肢体和躯干原发的软组织肉瘤患者中进行新辅助化疗。放疗与手术结合在软组织肉瘤的治疗中有确切的疗效。虽然预后并不因放疗和手术的先后顺序而异,但不良反应却存在差异。辅助放疗较新辅助放疗有更低的围手术期伤口并发症,但相对于新辅助放疗而言,辅助放疗需要更高的放射剂量,对长期功能的预后差于新辅助放疗。因此,我们相信围手术期放疗与化疗一样,在可能的情况下,应尽可能在术前进行。
Surgery is the definitive treatment for soft tissue sarcomas of the extremities and trunk, but is often unable to achieve long-term disease control in high-risk patients. The dominant mode of treatment failure is distant metastasis, with local relapse being secondary. Some patients with advanced local disease may be unresectable, or marginally so, and consequently face a poor prognosis.Peri-operative systemic therapy and radiotherapy may be able to enhance outcomes of surgical treatment. Peri-operative systemic therapy has been challenging to validate. Systemic therapy can lead to decreased tumor sizes. Validation of local control benefits in facilitating more conservative surgical procedures remains incomplete. For those with primary tumors judged difficult or impossible to resect, neoadjuvant chemotherapy may provide a route to local disease control.Peri-operative systemic therapy may also prevent development of metastatic disease. A recent study suggested benefit from adjuvant therapy with anthracycline/ifosfamide-based therapy, albeit in a post hoc reanalysis of a large trial. A randomized trial of neoadjuvant systemic therapy suggested that anthracycline/ifosfamide-based therapy may improve disease-free and overall survival in selected histologic sarcoma subtypes. This effect appeared mediated by improved distant metastasis-free survival, rather than improved local control. Methodological limitations in both trials necessitate further investigation. Nevertheless, we believe the results support the use of neoadjuvant systemic therapy in management of locally advanced soft tissue sarcomas of the extremities and trunk. Radiotherapy has a well-established position in conjunction with surgery for sarcomas treatment. While outcomes do not seem to vary depending on sequencing of radiotherapy administration versus surgery, adverse effects do so. Adjuvant radiotherapy is associated with lower peri-operative wound complication rates than neoadjuvant therapy, but the higher radiation doses required for adjuvant treatment yield long-term functional outcomes inferior to neoadjuvant radiotherapy. For this reason, we believe that peri-operative radiotherapy, like systemic therapy, should be administered neoadjuvantly, when possible.
Surgery is the definitive treatment for soft tissue sarcomas of the extremities and trunk, but is often unable to achieve long-term disease control in high-risk patients. The dominant mode of treatment failure is distant metastasis, with local relapse being secondary. Some patients with advanced local disease may be unresectable, or marginally so, and consequently face a poor prognosis.Peri-operative systemic therapy and radiotherapy may be able to enhance outcomes of surgical treatment. Peri-operative systemic therapy has been challenging to validate. Systemic therapy can lead to decreased tumor sizes. Validation of local control benefits in facilitating more conservative surgical procedures remains incomplete. For those with primary tumors judged difficult or impossible to resect, neoadjuvant chemotherapy may provide a route to local disease control.Peri-operative systemic therapy may also prevent development of metastatic disease. A recent study suggested benefit from adjuvant therapy with anthracycline/ifosfamide-based therapy, albeit in a post hoc reanalysis of a large trial. A randomized trial of neoadjuvant systemic therapy suggested that anthracycline/ifosfamide-based therapy may improve disease-free and overall survival in selected histologic sarcoma subtypes. This effect appeared mediated by improved distant metastasis-free survival, rather than improved local control. Methodological limitations in both trials necessitate further investigation. Nevertheless, we believe the results support the use of neoadjuvant systemic therapy in management of locally advanced soft tissue sarcomas of the extremities and trunk. Radiotherapy has a well-established position in conjunction with surgery for sarcomas treatment. While outcomes do not seem to vary depending on sequencing of radiotherapy administration versus surgery, adverse effects do so. Adjuvant radiotherapy is associated with lower peri-operative wound complication rates than neoadjuvant therapy, but the higher radiation doses required for adjuvant treatment yield long-term functional outcomes inferior to neoadjuvant radiotherapy. For this reason, we believe that peri-operative radiotherapy, like systemic therapy, should be administered neoadjuvantly, when possible.
引文
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[ 9 ] CAHLON O,BRENNAN M F,JIA X,et al.A postoperative nomogram for local recurrence risk in extremity soft tissue sarcomas after limb-sparing surgery without adjuvant radiation[J].Ann Surg,2012,255(2):343-347.
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[11] CALLEGARO D,MICELI R,BONVALOT S,et al.Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities:a retrospective analysis[J].Lancet Oncol,2016,17(5):671-680.
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