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Year : 2020  |  Volume : 16  |  Issue : 5  |  Page : 1177-1181

Chemotherapy combined with apatinib for the treatment of desmoplastic small round cell tumors: A case report

1 Department of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
2 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
3 Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

Date of Submission08-May-2020
Date of Decision15-Jun-2020
Date of Acceptance30-Aug-2020
Date of Web Publication29-Sep-2020

Correspondence Address:
Yanqing Li
Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_589_20

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 > Abstract 

Desmoplastic small round cell tumor (DSRCT) is a type of soft-tissue sarcoma with poor prognosis. Current treatments include multidisciplinary treatment options such as surgery, chemotherapy, and radiotherapy. Apatinib is an oral, small-molecule, anti-tumor, angiogenesis-targeted drug, which acts mainly on the intracellular binding site of vascular endothelial growth factor receptor-2. In this study, we administered apatinib in combination with chemotherapy to achieve good disease control. This is a 31-year-old male who presented with upper abdominal pain, nausea, and anorexia for over a month. Imaging revealed multiple solid masses and ascites in the liver and abdominal cavity. He was diagnosed as having cholangiocarcinoma with metastasis to the liver, both lungs, bone, and multiple lymph nodes in the neck, abdominal and pelvic cavity, retroperitoneum, and palpitate angle, based on a percutaneous biopsy of the liver and an abdominal mass, and other examinations. Computed tomography revealed disease progression after two cycles of gemcitabine combined with nedaplatin chemotherapy. Next-generation sequencing detection based on the Illumina high-throughput sequencing platform suggested EWSR1 exon7- Wilms tumor 1 exon8 fusion. The pathology was verified and diagnosed as DSRCT. The chemotherapy regimen was changed to cyclophosphamide, epirubicin, vincristine, and oral apatinib for two cycles. The lesions were mostly reduced, and partial response was evaluated. This case is the first report of the efficacy of apatinib combined with systemic chemotherapy in the treatment of DSRCT, which can become an alternative treatment for this disease.

Keywords: Apatinib, chemotherapy, desmoplastic small round cell tumor

How to cite this article:
Tian Y, Cheng X, Li Y. Chemotherapy combined with apatinib for the treatment of desmoplastic small round cell tumors: A case report. J Can Res Ther 2020;16:1177-81

How to cite this URL:
Tian Y, Cheng X, Li Y. Chemotherapy combined with apatinib for the treatment of desmoplastic small round cell tumors: A case report. J Can Res Ther [serial online] 2020 [cited 2021 Sep 22];16:1177-81. Available from: https://www.cancerjournal.net/text.asp?2020/16/5/1177/296439

 > Introduction Top

Desmoplastic small round cell tumor (DSRCT) is a very aggressive malignancy occurring mostly in young men. Most of the tumors originate in the pelvic cavity or abdominal cavity, and usually appear as peritoneal subserosal invasive masses. The pathological manifestations are nested small blue round cells surrounded by fibrous tissue, which express epithelial, neurogenic, and interstitial markers. The molecular feature is t (11;22) (p13;q12) chromosome translocation to produce Ewing sarcoma (EWS)-Wilms tumor (WT) 1 fusion protein.[1]

In terms of treatment, there are no standard clinical guidelines available. Current mainstream international treatment options include surgery, chemotherapy, and radiation therapy. However, new treatment strategies are urgently needed because the prognosis associated with DSRCT is still poor.[2] Apatinib (Hengrui Pharmaceutical Co., Ltd., Shanghai, China) is an oral tyrosine kinase inhibitor (TKI) that targets VEGFR-2 to block tumor growth and transfer. Good curative effects have been achieved in soft-tissue sarcoma, and it has a synergistic effect when combined with chemotherapy.[3],[4] However, there are no reports of apatinib combined with chemotherapy for DSRCT. Here, we report a case in which apatinib combined with chemotherapy was effective.

 > Case Report Top

A previously healthy 31-year-old male was admitted to the Department of Oncology of Shandong Provincial Hospital on July 12, 2019, due to paroxysmal epigastric pain, poor appetite, and nausea for more than 1 month. Physical examination revealed a slightly swollen upper abdomen, with mild tenderness and no tangible mass. Computed tomography (CT) on July 13, 2019 [Figure 1], [Figure 2], [Figure 3] showed multiple intrahepatic nodules, multiple masses within the abdominal cavity, and multiple nodules in the lungs. A colonoscopy was performed to rule out bowel malignancy. Whole-bone emission CT showed abnormal increase of radioactivity on right front ribs 6, 7, and 8, right acetabulum, and right upper femur. A serum test showed significant increase in cancer antigen (CA) 125 levels and a slight increase in neuron-specific enolase (NSE) [Figure 4]. A biopsy of the liver and abdomen was performed, and the pathology results showed poorly differentiated adenocarcinoma, which tended toward cholangiocarcinoma. Immunohistochemistry showed that the tumor cells were positive for CK [Figure 5], Vimentin [Figure 5], epithelial membrane antigen (EMA) [Figure 5], CK19, and CAM5. 2 [Figure 5] and negative for CD34, CD117, CK7, CK20, Villin, S-100, Hepatocyte, CK5/6, Syn, CgA, and Glypican-3. The Ki-67 proliferation index was 50%. We diagnosed the patient as having cholangiocarcinoma with pelvic and abdominal metastasis, peritoneal metastasis, multiple metastases to liver, bone, and lung, and multiple lymph node metastases. The patient received chemotherapy with 1000 mg/m 2 gemcitabine d1 and 8 and 40 mg/m 2 nedaplatin d1 and 2 for two cycles. Serum CA125 decreased significantly two cycles later and NSE decreased to within normal range [Figure 4]. CT [Figure 1], [Figure 2], [Figure 3] showed multiple nodules in both lungs, which were smaller than before and had partially disappeared. However, the intrahepatic lesions and multiple nodules in the abdominal and pelvic cavity were larger than before. Immunohistochemistry was performed at Peking University Third Hospital, with the following results: Desmin (+), WT-1 (−, anti-N-terminus), P53 (−), SMA (interstitial +), and NSE (foci +). Furthermore, the patient's DNA Illumina high-throughput sequencing report suggested EWSR1 gene exon7-WT1 exon8 fusion. CT of the chest and abdomen on November 21, 2019 [Figure 1], [Figure 2], [Figure 3] showed that most of the lesions had grown, and there was hydronephrosis in the right renal pelvis and ureter. Serum CA 125 and NSE levels had risen again [Figure 4]. However, the patient had no abdominal distension and no pain in the kidney area. We revised the diagnosis to DSRCT and performed chemotherapy with vincristine 2 mg d1, epirubicin 140 mg d1, and cyclophosphamide 1.0 d1 (VEC), combined with apatinib 0.25 g po qd. After 2, 4, and 6 cycles of VEC and apatinib, CT [Figure 1], [Figure 2], [Figure 3] showed multiple tumors of different sizes in both lungs, and abdominal and pelvic cavity, and most intrahepatic lesions had decreased. The patient showed good physical condition and had no obvious symptoms. VEC and apatinib therapy continued for 8 months up until now, and the patient showed no myelosuppression or other treatment-related side effects.
Figure 1: Lung computed tomography scans. (a and b) Before chemotherapy with 1st gemcitabine and nedaplatin administration (July 13, 2019) (c and d) After 2 cycles of gemcitabine and nedaplatin (October 05, 2019) (e and f) Before VEC and apatinib administration (November 21, 2019). (g and h) After 2 cycles of VEC and apatinib (January 17, 2020) (i and j) After 4 cycles of VEC and apatinib (April 20, 2020) (k and l) After 6 cycles of VEC and apatinib (July 30, 2020)

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Figure 2: Liver computed tomography scans (a-d) Before chemotherapy with 1st gemcitabine and nedaplatin administration (July 13, 2019) (e-h) After 2 cycles of gemcitabine and nedaplatin (October 05, 2019) (i-l) Before VEC and apatinib administration (November 21, 2019) (m-p) After 2 cycles of VEC and apatinib (January 17, 2020) (q-t) After 4 cycles of VEC and apatinib (April 20, 2020) (u-x) After 6 cycles of VEC and apatinib (July 30, 2020)

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Figure 3: Abdominal masses computed tomography scans (a and b) Before chemotherapy with 1st gemcitabine and nedaplatin administration (July 13, 2019) (c and d) After 2 cycles of gemcitabine and nedaplatin (October 05, 2019) (e and f) Before VEC and apatinib administration (November 21, 2019) (g and h) After 2 cycles of VEC and apatinib (January 17, 2020) (i and j) After 4 cycles of VEC and apatinib (April 20, 2020) (k and l) After 6 cycles of VEC and apatinib (July 30, 2020)

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Figure 4: Changes in CA125 and neuron-specific enolase. (a) Changes in CA125 (normal range within 0 ~45 U/ml). (b) Changes in neuron-specific enolase (normal range within 0 ~16.3 ng/ml) 2019.07.13: Baseline before therapy. 2019.09.07, 2019.10.05: After 1 and 2 cycles of GN. 2019.11.21: Before VEC and apatinib administration. 2019.12.19, 2020.01.17, 2020.03.14, 2020.04.20, 2020.06.06, 2020.07.30: After 1, 2, 3, 4, 5 and 6 cycles of VEC and apatinib. Ps: GN: Gemcitabine and nedaplatin. VEC: Vincristine, epirubicin, and cyclophosphamide

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Figure 5: Histological appearance and immunohistochemistry of desmoplastic small round cell tumor (Hematoxylin and Eosin stain), (a) ×100 magnification, (b) ×200 magnification, (c) CK, ×200 magnification, (d) Vimentin, ×200 magnification, (e) EMA, ×100 magnification, (f) CAM 5.2, ×100 magnification

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 > Discussion Top

DSRCT was first described by Gerald WL who reported 19 cases of intra-abdominal desmoplastic small cell tumor.[5] It mainly occurs in young adults or children, and the male-to-female ratio is approximately 4:1.[2],[6] The majority of cases originate in the abdominal cavity or pelvis, showing a large intra-abdominal mass with many peritoneal masses of various sizes. The disease is rare, with no specific symptoms.[7] Many well-defined nests, islands, or bands of small round cells surrounded by interstitial fibers can be seen under the microscope in typical cases.[8] Bleeding and necrotic areas can be seen inside the tumor, and there are obvious blood vessels of hyperplastic and hypertrophic stromal tumor in the bleeding area. Immunohistochemistry revealed that tumor cells expressed epithelial, mesenchymal, and neurogenic differentiation-related proteins. However, inexperienced pathologists may still misdiagnose this condition despite the above pathology characteristics. The diagnosis of this disease is based on the emergence of an EWS-WT1 gene fusion caused by t (11;22) (p13;q12) chromosomal translocation.[1] The present case was initially misdiagnosed as poorly differentiated cholangiocarcinoma. Fortunately, the genetic mutation was detected through genetic testing, which led us to make the correct pathological diagnosis. This experience also reminded us to consider the possibility of this rare disease in future clinical cases when encountering young male patients with multiple abdominal and pelvic spaces.

DSRCT is highly malignant and has a poor outcome. A retrospective analysis showed that the disease has a median overall survival (OS) of 25 months, a 3-year survival rate of 35%–37.5%, and a 5-year survival rate of <5%.[2],[6] Multimodal treatments may effectively improve patients' prognoses.

Surgery and chemotherapy remains the cornerstone of treatment. Complete surgery is an independent indicator related to prognosis.[9] Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may exert anti-tumor synergistic effects.[10],[11] A conventional-dose combination chemotherapy, high-dose chemotherapies with or without peripheral blood stem cell infusion can be used to treat the disease.[12],[13] In addition, whole abdominopelvic irradiation or intensity-modulated radiation therapy is also helpful for treatment.[14]

A retrospective study found that chemotherapy and CRS can improve OS.[11] This patient has no chance of surgery, so he was treated with vincristine, epirubicin, and cyclophosphamide, which is classic and economical. The chemotherapy regimen of gemcitabine combined with docetaxel also showed a therapeutic effect on the disease.[15] A chemotherapy of gemcitabine combined with nedaplatin showed partial reactivity after two cycles, which indicated a possible partial efficacy of the regimen.

Apatinib is an oral TKI with antiangiogenic properties targeting vascular endothelial growth factor receptor (VEGFR)-2. Furthermore, there are encouraging clinical data that confirm the effectiveness of apatinib for gastric cancer and other solid tumors.[16],[17] When combined with chemotherapy, apatinib has been proven to be safe and to prolong survival in the treatment of solid tumors and soft tissue tumors.[18],[19],[20] There was one case where apatinib was effective in treating DSRCT, and survival time with this drug alone was over 4 months; however, up to now, there have been no reports of apatinib combined with chemotherapy in the treatment of this disease.[21] We chose apatinib combined with chemotherapy considering the high degree of malignancy of DSRCT, the advantages of combination therapy, and the availability of the drugs. The patient was disease free for 5 months after applying this combination therapy with apatinib and it may continue to be effective. Remarkably, the patient did not show hypertension, proteinuria, or hand-foot syndrome which are common adverse reactions of apatinib.

Other promising targeted drugs include Pazopanib,[22],[23] a TKI targeting VEGFR; Trabectedin,[24],[25],[26] a synthetic anti-tumor drug derived from marine organisms that affects cell transcription and DNA repair; mammalian target of rapamycin-inhibitor temsirolimus,[27],[28] among others. However, these drugs are not as accessible or convenient as apatinib.

So far, no specific tumor markers related to the disease have been found. This patient's serum CA125 and NSE levels showed a significant downward trend with effective treatment, but gradually increased before the disease progressed, suggesting that the change in CA125 and NSE may be related to the therapeutic effect, which is similar to the conclusion of a case series report.[29] A case report in 2018 also showed similar findings regarding serum CA125 levels.[21] Notwithstanding the above, the correlation between CA125, NSE, and DSRCT still requires further experimental verification.

To our knowledge, this is the first valid case report of the use of apatinib combined with chemotherapy for the treatment of DSRCT, where it was determined that CA125 and NSE may be indicators of the degree of disease. More prospective studies are required in the future to verify the safety and efficacy of apatinib combined with chemotherapy, and more effective tumor markers need to be discovered.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

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