The current management of alveolar soft part sarcomas

Abstract

Objective:

Alveolar soft part sarcomas (ASPS) which has high potential ability of metastasis, is a rare and slowly growing malignant tumor, and mainly primary localized in limbs. To date, little is known about the best treatment of ASPS. This study aims to review the current management and advance of ASPS.

Methods:

WANFANG MED ONLINE, CNKI, and NCBI PUBMED were used to search literature spanning from 1963 to 2020, and all cases of ASPS about “ASPS, diagnosis, treatment, surgery, radiotherapy, chemotherapy, target therapy or immune therapy” with detailed data were included.

Results:

Complete surgical resection remained the standard management strategy, radiotherapy was reported to be used for the patients of micro- or macroscopical incomplete residue or the surgical margin was questionable. Chemotherapy was controversial. Some target drugs and immune checkpoint inhibitors had produced antitumor activity.

Conclusion:

Complete surgical resection is the cure treatment for ASPS, and adjuvant chemotherapy is not recommended excepted clinical trials. For the patients with micro- or macroscopical incomplete residue, radiotherapy should be appreciated. Furthermore, for recurrence, distant metastasis, and refractory of ASPS, combination therapy, especially combination with multiple target agents and/or immune checkpoint inhibitors may prolong survival time.

1. Introduction

Alveolar soft part sarcoma (ASPS) is a very rare soft tissue sarcoma, accounting for <1% of the all soft tissue tumor, and the 5-year overall survival (OS) is 56%.^[1] It mainly occurs in children and young adults, a few cases also present in elderly patients and pregnant women.^[2,3] Female patients are more than male patients, and the proportion is about 2:1.^[4] In children, the most common site of origin is the tongue and orbit of head-and-neck region, very few occurs in the penis.^[5] While, in adults patients, majority occur in deep areas of lower extremities and trunk, especially in thigh, but a few are also present in orbital, flexure tendon, breasts, lingual and gastrointestinal tract, and even in head.^[2,6–9] Since ASPS has no related symptoms in early time, most patients complain with a painless mass as a chief complaint, few patients also complain pain and discomfort accompanied the growing mass.^[4] ASPS has high potential ability of metastasis, lung, brain and bone metastases are common. Noteworthy, its brain metastasis ability is higher compared with other soft tissue sarcomas.

To date, due to its rarity, most reports of ASPS are case reports or small series. This narrative review was based on WANFANG MED ONLINE, CNKI, and NCBI PUBMED search spanning from 1963 to 2020, and all cases of ASPS about “ASPS, diagnosis, treatment, surgery, radiotherapy, chemotherapy, target therapy or immune therapy” with detailed data were included. Cases were excluded if they were duplicated or their information was too generalized.

2. Diagnosis

2.1. Imageological examination

ASPS which grows slowly is usually diagnosed as benigh tumor at the first medical examination. CT (Computed tomography) imaging shows an enhancing mass lesion with edge rule, and tortuous prominent blood vessels. On MRI imaging, ASPS usually typically shows high signal intensity in T1- and T2-weighted scan, and features internal and external multilobulated signal change. In contrast-enhanced MRI imaging, the mass shows intense enhancement and multiple peritumoral and intratumoral tortuous signal voids. The part with a high signal in T1-weighted MRI has low blood flow rate, and the part with multilobulated signal change in T1-weighted and T2-weighted MRI shows high blood flow rate, relatively.^[10–12]

2.2. Molecular pathology

Pathological photomicrograph shows that tumor cells which are arranged in alveolar or organoid pattern containing oval vesicular nuclei and abundant eosinophilic cytoplasm (Fig. 1, a photomicrograph of a 18-year old female patient with the primary tumor of the right thigh in our institution, which was approved by the institutional review board of Hebei Medical University and patient consent forms was obtained). In almost all cases, ASPS is characterized with rearrangement of TFE3 and der (17)t (X;17)(p11;q25), leads to ASPSCR1-TFE3 fusion gene.^[13,14]

Figure 1.

Photomicrograph of a 18-year old female patient with the primary tumor of the right thigh in our institution, which was approved by the institutional review board of Hebei Medical University and patient consent forms was obtained. The neoplasm showed the characteristic features of ASPS. A. × 100; B. × 400.

ASPS is easy to be misdiagnosed as arteriovenous malformation and benigh angioma, early biopsy is essential to differentiate it. Furthermore, perivascular epithelioid cell tumors (PEComas) which are a distinct set of mesenchymal tumors also with strong TFE3 expression and nested pattern morphologically mimicked ASPS in partly, and oncologist should avoid misdiagnosis.^[15]

3. Therapeutic methods

To date, complete surgical resection remains the standard management strategy, whereas, radiotherapy and chemotherapy are controversial, target drugs and immune checkpoint inhibitors have produced antitumor activity.

3.1. Surgery

Surgery is considered the first-line treatment in localized ASPS, complete surgical excision is the mainstay and the most effective therapeutic option, especially for primary intracranial and spinal ASPS.^[9,16] Surgical resection margin influences the prognosis, and wide resection for ASPS is strongly recommended. The 5-year OS rate of wide tumor resection could reached 67.5%.^[17] For R0 resection, the 3- and 5-year survival was 100% and 80% respectively, which were both higher than those of R1 or R2. It has to be noted, tumor size is also a prognosis factor. For patients with tumor size smaller than 50 mm, the survival was better than those with tumors size more than 50 mm (70% vs 42.9%) at final follow up.^[4] For patients with tumor size less than 50 mm, the 5-year, 10-year, 15-year survival rate were 72%, 65%, and 65%, respectively, which was better than those with tumor size larger than 50 mm (46%, 9%, and 0%, respectively).^[18] In a retrospective review of 26 consecutive ASPS patients, 20 patients underwent surgical excision (R0 18, R1 plus radiotherapy 2), no local recurrence was seen in these patients during a mean follow-up period of 81 months.^[19] Thus, extensive resection of the mass, especially R0 resection, is considered as the most effective treatment of ASPS.

3.2. Radiotherapy

Early studies reported no significant benefit from radiotherapy, more recent studies showed radiotherapy could prevent or reduce local recurrence (Table 1). Preoperative radiotherapy which is recommended for the treatment of STS in NCCN guideline could improve R0 resection rate and prolong OS for patients with extremity and retroperitoneal soft tissue sarcoma (STS) undergoing surgical resection.^[19,20] To date, radiotherapy was reported to be mainly used for the patients of micro- or macroscopical incomplete residue or the surgical margin with questionable. Hei et al^[7] reported 8 cases of orbital ASPS, 6 of those received postoperative radiotherapy, among them 5 cases demonstrated well prognosis with no evidence of local recurrence or metastasis during the follow-up period (range:3–61 months). For primary intracranial ASPS or brain metastasis of ASPS, gamma knife radiotherapy or SBRT could achieve satisfactory local control, the median progression-free survival (PFS) achieved 12 months after gamma knife radiotherapy.^[21]

Table 1.

Radiotherapy dose in ASPS.

Year	Author	Location	Dose	Effect
2016	Chen Z et al	Multiple brain metastases	Whole-brain radiotherapy with 30 Gy	Prognosis was poor
2014	Emmez H	Primary intracerebral ASPS	54 Gy (RT+ chemotherapy after gross total excision)	PFS achieved 45 mo
2014	Mullins BT	Larynx	Total dose of 59.4 Gy	DFS for 4 mo
2014	Mullins BT	Parotid gland	Total dose of 63.4 Gy	DFS for 168 mo
2014	Meng N	Recurrent ASPS of the tongue	Iodine-125	achieved CR +recurrent-free survival >30 mo
2013	Nakao K	The upper third of the vagina	carbon-ion RT with 67.2 Gy in 16 fractions	without recurrence for 20 mo
2010	Hanzer M	Single lung metastasis of ASPS	Hyperfractionated local RT with total dose of 44.8 Gy
2008	Sidi et al	The left thigh	50.4 Gy followed by a boost to the tumour area with 9 Gy (after chemotherapy + surgery)	Not well (bilateral pulmonary metastases immediately appeared)

For radiation doses, researchers recommended 50Gy following by boost to the tumor area with 10 to 16 Gy for negative margins, 16 to 18 Gy boost for microscopically positive margins and 20 to 26 Gy for gross residual disease of soft tissue sarcoma of trunk after operation,^[22–24] which had been recommend in NCCN guide (National comprehensive Cancer Network, https://www.nccn.org). For multiple brain metastases, some researchers administered palliative whole-brain radiotherapy with 30 Gy in 10 fractions, but prognosis was poor because of the widespread metastases in advanced cases.^[25] For single lung metastasis of ASPS, hyperfractionated local radiotherapy could be considered with total dose of 44.8 Gy.^[26]

Carbon-ion radiotherapy also showed satisfactory effects. There was a case report that a 9-year old girl who was diagnosed as ASPS with the tumor locating in the upper third of the vagina, received carbon-ion radiotherapy with 67.2 Gy in 16 fractions at the part of the tumor adhered to the posterior pubis which was residual after resection, the tumor decreased gradually without recurrence for 20 months, the patient had not any adverse effects.^[27] In addition, iodine-125 may be beneficial for some recurrent ASPS patients. A report showed a 4-year-old boy with recurrent ASPS of the tongue who received iodine-125 seed brachytherapy under ultrasound guidance, achieved complete response (CR) and had a recurrent-free survival of >30 months.^[28] Thus, for some local lesions of ASPS, iodine-125 could be considered.

3.3. Chemotherapy

To date, the efficacy of chemotherapy on ASPS was reported ineffective.^{[8,21,29–32]} Reichardt et al^[29] retrospectively analyzed the response on first-line chemotherapy in 68 patients of ASPS, results showed 51% was progress disease (PD), 41%was stable disease (SD), only 4% of patients was CR. It means that chemotherapeutic regimens lack efficacy in ASPS. They suggested ASPS patients should not be treated with chemotherapy outside of controlled clinical trials. Flores et al^[30] analyzed the clinical data of 69 children and young adults less than 30 years old with ASPS, they found ASPS was resistant to cytotoxic chemotherapy. In the EpSSG NRSTS 2005 study, 4 of 22 patients with ASPS received chemotherapy of ifosfamide and doxorubicin, there were no responses.^[31]

Whereas, few case reports demonstrated the well clinical efficacy of chemotherapy. Asokan et al^[33] reported an 18-year-old female of ASPS combined pulmonary metastasis received 6 cycles of chemotherapy with adriamycin, cyclophosphamide and vincristine. No locoregional recurrence or metastasis elsewhere was found during the 11 months follow-up. Qiu et al^[5] reported an unusual case of ASPS involving the penis of a 3-year-old boy who just received a partial penectomy, received 6 months of chemotherapy with ifosfamide, epirubicin, mesna and dacarbazine. PFS was 28 months. These were similar to Lin YK'study^[17] who performed a retrospective study enrolling 13 ASPS patients, 7 of those patients received chemotherapy with an alkylating agent (ifosfamide) and doxorubicin, the 5-year survival rate was 66.7%. Emmez et al^[22] reported a primary intracerebral alveolar soft part sarcoma in an 11-Year-Old Girl who received whole brain radiotherapy and 9 cycles of chemotherapy using the regimen of ifosfamide, vincristine, actinomycin after gross total excision, 45 months after the initial treatment, MRI showed recurrence, then she received re-operation and 6 cycles of ifosfamide, carboplatin, and etoposide chemotherapy regimen, no recurrence was found during 9 months follow-up. These results mean that chemotherapy may play a beneficial role in long-term survival of ASPS. But many published studies are case reports or small series encompassing diverse treatment paradigms. Thus, more data from systematic analyses and clinical trials of chemotherapy are needed. So adjuvant chemotherapy is not recommended excepted clinical trials.

3.4. Targeted therapy

An increasing number studies of targeted therapy in ASPS have been published which report multi-targeted tyrosine kinase inhibitors are effective for ASPS, especially for patients with evidence of metastasis, but most are case report or small series ^[32,34–43] (Table 2). To date, sunitinib, pazopanib have been recommended for the treatment of ASPS in NCCN and Chinese society of clinical oncology (CSCO) guidelines. Anlotinib, a novel tyrosine kinase inhibitor targeting VEGF/VEGFR signaling involving VEGFR-2,-3 and FGFR-1,-2,-3,-4, as the first agent to be approved for clinical use, was approved by China Food and Durg administration (CFDA)and recommended for the first-line therapy of ASPS in CSCO guidelines of STS. The recommendation of Anlotinib was based on a phase II study which was a multicenter study from 15 institutions across China.^[35] In this study, 166 patients who received oral anlotinib 12 mg, once daily for 2 weeks, 3 weeks as a cycle, were included, and 13 cases was ASPS patients. The primary endpoint was PFR at 12 weeks (PFR12 weeks). Results showed PFR12 weeks was 68%, and the median PFS and OS was 5.6 and 12 months respectively. For ASPS group, it was 77% and 21 months respectively, median OS had not been reached. No treatment-related death occurred. It suggests that anlotinib has significant benefit and the toxicity is manageable and acceptable. A double-blind, placebo-controlled, phase III trial of anlotinib in ASPS is ongoing (NCT03016819, Table 3).

Table 2.

Clinical trials evaluating target drug in ASPS.

Year	Author	Phase and clinical number	Drug	Effect
2019	Judson I et al	II (NCT01337401)	Cediranib 30 mg qd Cediranib VS placebo group	median PFS: 10.1 VS 4.9 (P = .28)12-mo PFS: 38.7% VS 34.4%median OS: 27.8 Vs 47.3 (P = .48)12-mo OS: 90 3% VS 68.8%
2019	Cohen JW et al	II (NCT00942877)	Cediranib (AZD2171)	ORR 35% at 24 wks, DCR 84% at 24 wks
2019	Kim M et al	II (NCT02113826)	Pazopanib 800 mg qd	median PFS 5.5 mo, 6-month PFS 50%
2018	Chi Y et al	II (NCT01878448)	Anlotinib 12 mg, qd	median PFS 5.6 mo, PFS 12 wks was 77% median OS 12 mo
2018	Schöffski et al	II (EORTC 90101) (NCT01524926)	Crizotinib 250 mg	1-year OS was 97.4% and 75.0% for MET+ and MET- patients
2018	Stacchiotti et al	Retrospective study	Pazopanib	median PFS for 13.6 months
2017	Schuetze et al	II (NCT00464620)	Dasatinib	PFS rate at 6 mo with 62% for ASPS
2017	Jagodzinska-Mucha P et al	Retrospective study (15 patients with metastatic ASPS)	Sunitinib 37.5 mg qd	median PFS reached 19 mo, median OS for 56 mo
2016	Li T et al	Retrospective study (14 patients with unresectable or metastatic ASPS)	Sunitinib 37.5 mg qd	median PFS for 41.0 mo, median OS not reached
2016	Kuo DJ	Case report (2 patients with widespread metastases)	Pazopanib, sorafenib, cediranib and sunitinib	survived over 5 y
	Kuo DJ	(multiple target agents)	Sorafenib, cediranib, pazopanib, sunitinib, axitinib, cabozantinib	survived over 5 y
2012	Wagner AJ et al	phase II trial (NCT00557609)	Tivantinib (ARQ 197) ASPS (n = 27)	median PFS was 5.5 mo for ASPS
2011	Stacchiotti et al	9 metastatic ASPS patients	Sunitinib 37.5 mg qd	the median PFS reached 17 months

Table 3.

Ongoing clinical trials with target therapy in ASPS.

Trial number	Phase	Drug	Disease	Primary endpoint	Status completion date
NCT02867592	II	XL184 (Cabozantinib)	Refractory Sarcomas (ASPS)	OR Active, not recruiting	September, 2021
NCT01391962	II	Sunitinib or Cediranib	Metastatic ASPS	ORR Active, not recruiting	December, 2021
NCT03016819	III	Anlotinib (AL3818) or Dacarbazine	Metastatic or Advanced ASPS	ORR Recruiting	August, 2021

Pazopanib, another small molecule and multitargeted tyrosine kinase inhibitor to against VEGFR was also reported to be effective for ASPS.^[8,36–38] In a phase II trial, 6 enrolled patients with metastatic ASPS received pazopanib 800 mg once daily, One patient achieved partial response (PR) (objective response rate 16.7%) and the others showed SD.^[37] The tumors of patients with SD remained stable for at least 4 months. The median PFS was 5.5 months, and the 6-month PFS rate was 50%. There was no severe toxicities except 1 patient with grade 3 diarrhea. A retrospective study reported 30 patients received pazopanib, 1 case achieved CR, 7 reached PR, 17 with SD, the median PFS was 13.6 months.^[38] Whereas, 1 case report showed pazopanib could efficiently prolong survival time over 3 years after chemotherapy failure on a 37-year-old female presented with multiple lung mass and a large abdominal tumor, but seemed ineffective for brain metastasis because of it might not pass through the blood-brain barrier.^[31]

Sunitinib was reported to be promising efficacy for ASPS.^[39–41] In a retrospective study, sunitinib was administered to metastatic ASPS patients, and the median PFS reached 17 months.^[39] Jagodzińska-Mucha et al^[40] reported 15 metastatic ASPS patients, and the median PFS and OS reached 19 months and 56 months respectively. The 5-year OS was 49%. In another retrospective study of 14 Chinese patients with locally unresectable or metastatic ASPS, treated with 37.5 mg of sunitinib once daily, the median PFS was 41.0months, and median OS was not reached. The 1- and 4-year OS were 90.0% and 60.0% respectively. Furthermore, neoadjuvant treatment with sunitinib could improve the chance of resection for patients with locally advanced ASPS.^[41]

To date, other target drugs, such as crizotinib,^[42] cediranib,^[43–46] bevacizumab^[47,48] sorafenib,^[49] cabozantinib,^[49] apatinib,^[50] dasatinib^[51,52] and Tivantinib,^[53] have also shown therapeutic advantages and great potential for ASPS patients. The famous clinical trial is EORTC (European Organization for Research and Treatment of Cancer) 90101 study which is a multicentre, biomarker-driven, single agent, nonrandomized, two-stage phase II trial to evaluate the efficacy and safety of crizotinib (a MET tyrosine kinase inhibitor) in advanced and/or metastatic ASPS patients with rearrangement of TFE3.^[42] In this study, 48 patients who were attributed to MET+(43/48 patients), or MET- (4/4 patients) sub-cohorts (1 MET? Patient) on the basis of the presence or absence of a TFE3 gene rearrangement, received the treatment with oral crizotinib with starting dose as 250 mg bid, 21 days was defined as 1 treatment cycle. Results showed the objective response rate in MET+ and MET- patients was 2.5% and 25.0%, respectively. The SD in MET+ and MET- patients was 87.5% and 75.0%, respectively. The disease control rate was 90% and 100%, respectively. The 1-year overall survival rate was 97.4% and 75.0%, respectively. There were no deaths on treatment or within 4 weeks of treatment discontinuation. This study demonstrated that crizotinib had safety and activity in TFE3 rearranged ASPS patients.

Cediranib (AZD2171), another oral, small-molecule anti-angiogenic agents, could inhibited all 3 vascular endothelial growth factor receptor (VEGFR-1, -2and -3). In a phase II trial, the OR rate of cediranib reached 35% and disease control rate reached 84% at 24 weeks.^[43–45] In another phase II trial, which recruited 48 advanced ASPS patients, PFS was 10.1 months in Cediranib group which was longer than that in placebo group (4.9 months), and the adverse sides were tolerated.^[46]

All of the above suggest that targeted therapy is effective for the long survival of ASPS patients, especially for patients with evidence of metastasis. Unfortunately, most target drugs have not yet been approved for use in ASPS. Some phase II and III clinical trials are ongoing (Table 3), and results are expected in the near future.

3.5. Immune therapy

Immune checkpoint inhibitors (ICIs), such as anti-PD-1 (programmed death-1) anti-PD-L1, and anti-cytotoxicT lymphocyte antigen 4 (CTLA-4), are increasingly used in late-stage malignant tumor patients who have failed to respond to multiple treatments, such as melanoma, non–small-cell lung cancer (NSCLC), and renal cell carcinoma, and have produced higher antitumor response.^[54–56] In ASPS patients, there are just some case reports for ICIs. Kuo et al^[49] reported 2 ASPS cases, 1 patient received nivolumab (PD-1 inhibitor) after failed treatment with multiple target drugs, the SD achieved for 7 months. Lewin et al^[57] reported 2 ASPS patients who received immune checkpoint inhibitor, durvalumab (anti-PD-L1) alone or in combination with tremelimumab (anti-CTLA-4) achieved sustained partial responses. Another case report showed a 29-year-old man who was commenced an ipilimumab (ananticytotoxicT-lymphocyte antigen 4) plus nivolumab (anti-PD-1) combination therapy after failed treatment with surgical extirpation and multiple target drugs, results revealed the patient achieved a partial response after 4 cycles of this combination therapy, and the tumor continued with a 69% decrease from baseline imaging after 3 cycles of maintenance nivolumab.^[58] Atezolizumab, a monoclonal anti-PD-L1 antibody, was also reported to be effective for ASPS with multiple brain metastases, but researchers found that RECIST criteria may be not fit for evaluating the curative effect after treatment with ICIs.^[59] These results suggest that immune checkpoint blockade may be a useful therapeutic strategy for advanced ASPS with widespread metastases. Up to now, just pembrolizumab was recommended for the treatment of ASPS in NCCN and CSCO guidelines. The recommendation of pembrolizumab was based on a retrospective review, which reviewed the charts of 50 sequential patients with metastatic or unresectable advanced sarcoma, and all 4 ASPS patients had clinical benefit with checkpoint inhibitors.^[60] Now Some clinical trials are ongoing (Table 4), and we expect exciting results.

Table 4.

Ongoing clinical trials with PD-1/PD-L1 inhibitors in ASPS.

Trial number	Phase	Drug	Disease	Primary	Status endpoint	Completion date
NCT03141684	II	Atezolizumab (Anti-PD-L1)	Advanced ASPS (initial treatment)	ORR	Recruiting	October, 2021
NCT02936102	I	FAZ053 (Anti-PD-L1) or+PDR001 (Anti-PD1)	Advanced ASPS	Adverse	Active Events (AEs), not recruiting	April, 2022
NCT03623581	II	GB226 (Anti-PD-1)	Relapsed/metastatic/unresectable ASPS	ORR	Recruiting	December, 2022

3.6. Combination therapy

To date, little is known about the combination therapy, such as chemotherapy combined with radiotherapy and/or target therapy or immune therapy. Palliative radiotherapy combined with chemotherapy is considered appropriate for ASPS patients with multiple brain or lung metastasis.^[61] Multiple target agents are also reported to be effective for ASPS. Kuo et al^[49] reported 2 ASPS patients with widespread metastases, who were both administered multiple target agents (1 case was treated with pazopanib, sorafenib, cediranib and sunitinib. another was treated with sorafenib, cediranib, pazopanib, sunitinib, axitinib, cabozantinib), they both survived over 5 years. Furthermore, ICIs combination therapy, such as anti-PD-L1 combined with anti-CTLA-4 has shown promising activity and efficacy.^[58] Clinical trials of combination therapy are ongoing, it maybe a promising treatment in ASPS (Table 5). More systematic studies are needed to validate that findings and examine the efficacies of other new single and combination therapy regimens.

Table 5.

Ongoing clinical trials of combination therapy in ASPS.

Trial number	Phase	Drug	Disease	Primary endpoint	Status completion date
NCT03880123	I	Selinexor and Ixazomib	Advanced Sarcoma (ASPS)	MTD	Withdrawn November 2020
NCT01532687	II	Gemcitabine Alone or in Combination With Pazopanib	Refractory STS (ASPS)	PFS	Completed October, 2019
NCT02636725	II	Concurrent Axitinib and Pembrolizumab	Advanced ASPS	PFS	Active, December, 2022 not recruiting
NCT03989596	II	Hypofractionated RT (10x 3.25 Gy) and Deep hyperthermia	Unresectable STS (ASPS)	Rate of grade 3	Active, December, 2022 not recruiting
NCT03277924	I/II	Sunitinib Plus Nivolumab	Advanced STS (ASPS)	PFSR at 6 months	Recruiting September, 2022
NCT04332874	II	Pembrolizumab + infusion of melphalan and dactinomycin	Advanced ASPS	PFS	Recruiting April, 2023

4. Conclusion

Because of the low incidence of ASPS, there are inherent limitations of systematically studying such a rare malignant tumor. Many published studies are case reports or small series encompassing diverse treatment paradigms. Additionally, no meta-analysis has yet to analyze the benefit of adjuvant therapy treatment, and of how it should be coordinated with radiation therapy. Thus, more data from systematic analyses and clinical trials are needed.

In summary, ASPS is a rare malignant tumor, complete surgical resection is the mainstay of treatment for localized ASPS, and adjuvant chemotherapy is not recommended excepted clinical trials. For the patients with micro- or macroscopical incomplete residue or the surgical margin was questionable, radiotherapy should be appreciated to prevent or reduce local recurrence, targeted therapy shows significant benefit for ASPS. Furthermore, for recurrence, distant metastasis, and refractory of ASPS, combination therapy, especially combination with multiple target agents and/or immune checkpoint inhibitors may prolong the mean survival time.

Author contributions

Data curation: Yuehong Li.

Resources: Liubing Hou.

Software: Huandi Zhou, Liubing Hou.

Writing – original draft: Xiaojing Chang.

Writing – review & editing: Xiaojing Chang, Xiaoying Xue.