High-dose chemotherapy followed by autologous stem cell transplantation for adult patients With first relapse of Ewing's sarcoma: A single institution experience.

The prognosis of patients with Ewing's sarcoma family of tumors (ESFT) relapse is poor; the 5-year overall survival (OS) is 13%. We evaluated the effectivity of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in adult patients with ESFT relapse. Between January 2010 and January 2021, we retrospectively analyzed 20 patients with ESFT who received HDT upon relapse. A combination of busulfan with melphalan was used as a conditioning regimen before ASCT. The median follow-up from diagnosis and from first relapse was 46.08 months (range; 10.71-186.87) and 14.41 months (range; 4.34-104.11), respectively. The median of age patients was 21.2 years (range, 17.6-25.3), and 10 (50%) patients were female. The tumor originated from the bone in 13 patients and soft tissue in 7 patients. Twelve patients had early (<2 years) relapse, and 8 patients had late (>2 years) relapse. Before HDT, 13 (65%) and 7 (35%) patients had pulmonary and extrapulmonary metastasis, respectively. After induction chemotherapy, 14 patients achieved complete response. The median OS1 and OS2 were 51.6 months (95% confidence interval [CI], range: 16.2-87) and 15.7 months (95% CI, range: 10.2-21.2), respectively. The 1-, 2-, and 5-year OS rates were 50%, 30%, and 15%, respectively. One patient died (sepsis) 1 month after ASCT. In univariate analyses, a disease-free interval (DFI) of < 2 years (P = .008) and incomplete response (P = .021) before ASCT were poor prognostic factors for OS2.HDT with ASCT can result in long-term survival of patients with ESFT relapse. HDT should be considered an important treatment opt ion in patients with a DFI > 2 years and complete response before transplantation.

A rare entity of Primary Ewing sarcoma in kidney.

BACKGROUND: Ewing sarcoma (ES) or primitive neuroectodermal tumors (PNET) represents a spectrum of poorly differentiated and aggressive malignancies. It rarely arises from the kidney and accounts for less than 1% of renal mass. Given the uncharacteristic clinical symptoms and imaging features, renal Ewing sarcoma (RES) is often diagnosed by postoperative pathology. CASE PRESENTATION: Herein, we depicted a case of RES, which was administrated in our institution by chief complaints of intermittent left plank pain and palpable abdominal mass. We demonstrated the aggressive behavior of this renal malignancy and summarized its therapeutic modalities and outcomes. CONCLUSION: The diagnosis of RES relies on integrated analysis including histomorphology, immunohistochemical staining and confirmation of molecular-genetic testing. Despite the surgery and adjuvant therapy, optimized and potent therapeutic regimes are still urgently needed to improve the poor prognosis of RES.

Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor.

Peripheral primitive neuroectodermal tumors (PNETs) constitute very rare and aggressive malignancies. To date, there are no standard guidelines for management of peripheral PNETs due to the paucity of cases arising in various body sites. Therapeutic approach is derived from Ewing sarcoma family, which currently remains multimodal. Our study retrospectively analyzed 86 PNET patients from February 1, 1998 to February 1, 2018 at Peking Union Medical College Hospital with an additional 75 patients from review of literature. The clinicopathologic and treatment plans associated with survival was investigated. Surgery, chemotherapy, female sex, small tumor size, no lymph node metastasis, R0 surgical resection, (vincristine + doxorubicin + cyclophosphamide)/(isophosphamide + etoposide) regimen, and more than 10 cycles of chemotherapy were associated with improved overall survival in univariate analysis. Surgery, more than 10 cycles of chemotherapy, and small tumor size were independent prognostic factors for higher overall survival. Our data indicates that multimodal therapy is the mainstay therapeutic approach for peripheral PNET.

[Six-year disease-free survival after chemotherapy treatment for metastatic renal peripheral neuroectodermal tumor]. / Six ans de survie sans progression après chimiothérapie pour une tumeur neuro-ectodermique périphérique rénale métastatique.

Peripheral neuroectodermal tumors (PNET) of the kidney are extremely rare. They are often diagnosed at a late stage due to their nonspecific clinical presentation. Treatment of patients with metastases is based on palliative chemotherapy. We here report a case of PNET of the kidney with sudden onset of metastases to the lymph nodes and to the skin. The patient showed good clinical and radiological response and experienced progression-free survival at 6 years after polychemotherapy with vincristine, doxorubicin and cyclophosphamide.

Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumors in Bronchus.

Ewing sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET), a member of the Ewing sarcoma family of tumors, is a malignant soft tissue tumor with small undifferentiated neuroectodermal cells. Primary trachea-bronchial ES/pPNET is very rare. The most common pulmonary ES is due to a metastasis. We describe a case of ES/pPNET which originated in the left basal trunk bronchus. The patient was a 30-year-old male, presenting with irritable cough and fever for 10 days. A tumor of 60 mm in diameter was found in the left basal trunk bronchus, extending to the left lower lobe. No distant metastases were detected. Histopathological examination revealed a malignancy of ES/pPNET with a diffuse proliferation of round cells, a Flexner-Wintersteiner rosette formation and positive staining for CD99. The patient was successfully treated with a combination of left lower lobectomy and adjuvant chemotherapy and has remained disease-free for approximately 18 months at follow-up. This case highlights that ES/pPNET should be considered as a differential diagnosis in cases of trachea-bronchial tumors.

[The treatment and prognosis of peripheral primitive neuroectodermal tumor].

Objective: To evaluate the treatment and prognosis of peripheral primitive neuroectodermal tumor (pPNET). Methods: From March 2006 to April 2015, 47 patients with pPNET who had undergone chemotherapy in our hospital were enrolled. The clinical data and survival information of these patients were collected and interpreted retrospectively to analyze the effect of each treatment on the survival of patients. Results: The median overall survival (OS) for whole group was 23.5 months, and 5-year survival rate was 33.8%. In the patients who underwent radical surgery, the median OS was 70.4 months, the 5-year survival rate was 54.4%, the median disease-free survival (DFS) was 23.1months, and 5-year DFS rate was 34.4%. Sixteen patients had recurrences or metastasis after surgery. Eighty-one percent of them (13/16) occurred within 2 years after surgery. The difference of median OS between patients who got adjuvant chemotherapy and those who did not was statistically significant (P=0.04). But the difference of median PFS between these two groups was not statistically significant (P=0.057). There was no statistically significant difference for median OS (P=0.619) and median DFS (P=0.191) between patients who got adjuvant radiotherapy and those who did not. The recurrence rate between these two groups was not statistically significant (P=0.40). The median OS and PFS for 34 patients who received first-line palliative chemotherapy was 10.7 months and 3.2 months. 1-year and 2-year survival rates were 48.0% and 17.8%. The response rate and clinical benefit rate for first-line chemotherapy was 53.1% and 75.0%. The median PFS and OS for patients who received platinum-based regimens were 3.3 months and 14.5 months. The median PFS and OS for patients who got non-platinum regimens were 2.7 months and 10.3 months. There was no significant difference of PFS and OS between platinum-based and non-platinum regimens. Palliative surgery and radiotherapy did not improve the OS of pPNET this cohort. Conclusions: Comprehensive treatment including chemotherapy, radiotherapy and surgery is the standard treatment model for early pPNET patients. Adjuvant chemotherapy significantly improved the overall survival of early pPNET patients. Chemotherapy is the main treatment for patients with advanced pPNET. Platinum-based chemotherapy seem to be a good option.

Primitive neuroectodermal tumour of the cervix: a rare diagnosis.

A 48-year-old woman presented with symptoms of lower abdominal pain and vaginal discharge for 6 months. Clinical examination and pelvic ultrasound scan suggested a diagnosis of infected Gartner's cyst, for which she underwent vaginal cystectomy. However, histopathology and immunohistochemistry revealed a diagnosis of primitive neuroectodermal tumour of the cervix. Further investigations revealed the stage to be FIGO IIIB, which was inoperable. She received neoadjuvant chemotherapy (vincristine, adriamycin, cyclophosphamide alternating with ifosfamide, cisplatin and etoposide, every 21 days), but the tumour did not respond to treatment and she was started on radiotherapy with definitive intent (55.8 Gray in 31 fractions over 6.2 weeks). A PET-CT performed 2 months after completion of radiotherapy showed complete response, and she is now receiving adjuvant chemotherapy.

Antiangiogenic therapy for primitive neuroectodermal tumor with thalidomide: A case report and review of literature.

RATIONALE: Peripheral primitive neuroectodermal tumor (PNET) is a kind of small round cell tumor derived from primitive neuroectodermal tumor. PATIENT CONCERNS: PNET is a highly malignant tumor that is subordinated to Ewing sarcoma. It occurs predominantly in soft tissue and bone and rarely in the bronchi and lung. Traditional surgery, radiotherapy, and chemotherapy are used for the treatment of PNET, but are usually ineffective. DIAGNOSES: There was a rare case of a 17 year-old man diagnoses with primary pulmonary PNET. INTERVENTIONS: The patient was treated by the remedy treatment with thalidomide after the poor effect of conventional radiotherapy and chemotherapy. OUTCOMES: The patient survived without disease progression for 15 months and was in stable condition. LESSONS: Thalidomide provides a choice for maintenance therapy in PNET.

Metastatic malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): results with PNET-based chemotherapy.

BACKGROUND: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin-based chemotherapy. Postchemotherapy teratoma can usually be surgically resected. However, teratoma, which is pluripotent tissue, can undergo malignant transformation along mesodermal elements to primitive neuroectodermal tumor (PNET). Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with malignant transformation to PNET with cyclophosphamide+doxorubicin+vincristine (CAV) alternating with ifosfamide+etoposide (IE). METHODS: We reviewed 86 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2012. We identified 18 patients who were treated with chemotherapy comprising cyclophosphamide (1000 to 1200 mg/m), doxorubicin (50 to 75 mg/m), and vincristine (2 mg) alternating with ifosfamide (1.8 g/m) plus etoposide (100 mg/m) for 5 consecutive days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoietic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. RESULTS: Twelve patients had unresectable disease and 6 were treated in an adjuvant setting. Median age was 29 years (range, 20 to 53 y). Nine of the 12 metastatic patients achieved objective response by RECIST criteria. Six of those were rendered with no evidence of disease (NED) with further surgery. Although 4 of the 6 patients subsequently relapsed, 1 patient remains alive and NED at 78 months. The 6 patients who received adjuvant treatment are alive with NED at 9 to 90 months with a median duration of 32.7 months. CONCLUSIONS: CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long-term disease-free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.

[Clinical efficacy of CCG7942/POG9354 protocol in treatment of peripheral primitive neuroectodermal tumor in children].

OBJECTIVE: To investigate the clinical manifestations, diagnosis, and treatment of peripheral primitive neuroectodermal tumor (pPNET) in children and the survival of patients treated with the CCG7942/POG9354 protocol. METHODS: A retrospective analysis was performed on the clinical data of 10 patients with pPNET admitted from October 2008 to October 2013. Of the 10 patients, 3 had metastasis, while others had no metastasis. The 7 patients without metastasis were treated with the Children's Cancer Study Group 7942 (CCG7942) protocol, and the other 3 patients with metastasis with the Pediatric Oncology Group 9354 (POG9354) protocol. The therapeutic response and chemotherapy-related toxicities were evaluated by WHO criteria and Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: In the 7 patients treated with the CCG7942 protocol, 4 achieved a complete remission (CR), 1 had stable disease, 2 developed progressive disease (PD), and 2 had recurrence. In the 3 patients treated with the POG9354 protocol, 1 achieved a CR, 2 developed PD, 2 had recurrence, and 2 died. For the 7 patients without metastasis, the survival time was 5-60 months, and the event-free survival rate was 71%. For the 3 patients with metastasis, the survival time was 13-25 months, and the event-free survival rate was 33%. All patients developed grade 4 bone marrow suppression, and other grade 1-2 toxicities, including gastrointestinal reactions, liver function impairment, and renal function impairment, were also seen. CONCLUSIONS: CCG7942 protocol is effective and safe for children with non-metastatic pPNET. However, POG9354 protocol has unsatisfactory efficacy in children with metastatic pPNET, so further studies are needed to improve the therapy for this disease.

Circulating T-regulatory cells in PNET: a prospective study.

PURPOSE: Bone marrow regulatory T-cells (Tregs) have been evaluated in patients with peripheral neuroectodermal tumor (PNET); data on peripheral blood circulating Tregs are lacking. The objective of our study was to determine baseline Tregs (both Treg frequency and absolute number) in patients with PNET and correlate with patient characteristics, and observe their change with treatment and relapse. METHODS: Five milliliters blood was evaluated in de novo patients with PNET at diagnosis, post-neoadjuvant chemotherapy and at relapse/progression, along with nine healthy controls using flow-cytometric analysis for Treg cells (CD4+ CD25+ FoxP3+). RESULTS: Thirty-seven patients with median age 17 years; male/female ratio 5.1:1 had significantly higher baseline absolute Tregs than controls (mean 338.95 ± 264.63/mm(3) vs. 34.83 ± 24.90/mm(3); P < 0.001). Patients with fever had a significantly higher mean Treg frequency than those without fever (11.27 ± 8.36% vs. 8.40 ± 2.58%; P = 0.014). There was significant reduction in the circulating Tregs after neoadjuvant chemotherapy (mean 339.78 ± 294.31/mm(3) vs. 82.09 ± 91.25/mm(3), P < 0.001) and rise at progression (n = 13) as compared to values post-neoadjuvant chemotherapy (mean 240.92 ± 191.90/mm(3) vs. 57.67 ± 39.01/mm(3), P = 0.012). There was no significant difference in the event-free survival (EFS) or overall survival (OS) between the high and low Treg cell groups (2-year EFS 51.6% vs. 52.1%; P = 0.689 and OS 61.3% vs. 59.2%; P = 0.891). CONCLUSION: This study on circulating Tregs in PNET demonstrated that peripheral blood Tregs are higher in patients than healthy controls. There was significant reduction in Tregs with chemotherapy and rise at progression.

Irinotecan, vincristine, cisplatin, cyclophosphamide, and etoposide for refractory or relapsed medulloblastoma/PNET in pediatric patients.

PURPOSE: The treatment outcome of pediatric refractory or relapsed brain tumor is very dismal, and effective salvage chemotherapy is not established. The combination of irinotecan, vincristine, cisplatin, cyclophosphamide, and etoposide was administered to pediatric patients with refractory or relapsed brain tumors as a salvage treatment at our institution. METHODS: The combination regimen was administered since June 2006 and consisted of irinotecan (300 mg/m(2), d0), vincristine (2 mg/m(2), d0), cisplatin (60 mg/m(2), d0), cyclophosphamide (1,000 mg/m(2), d1), and etoposide (100 mg/m(2)/day, d0-2). Patients could concurrently receive radiotherapy, surgery, and/or high-dose chemotherapy and stem cell rescue. The medical records of all patients were retrospectively analyzed. RESULTS: Thirteen patients with refractory or relapsed brain tumor were included (medulloblastoma, n = 12; central nervous system primitive neuroectodermal tumor, n = 1). Median time from diagnosis to this combination chemotherapy was 30 months (range, 3-111 months), and median cycle administered was four cycles (range 1-22 cycles). Objective tumor response at the end of chemotherapy was 38.5 % including three patients with complete response and two with partial response. One patient showed complete response and achieved long-term survival with this combination chemotherapy, and two patients achieved long-term survival with multimodality treatments. There was no grade III or IV toxicity related to this combination chemotherapy except for thrombocytopenia and neutropenia. CONCLUSIONS: The combination of irinotecan, vincristine, cisplatin, cyclophosphamide, and etoposide may produce objective responses in pediatric patients with refractory or relapsed medulloblastoma or primitive neuroectodermal tumor.

Outcomes after interdisciplinary management of 7 patients with Askin tumor.

PURPOSE: Askin tumors are rare but highly malignant chest wall tumors, which require multimodal therapy including often extensive resection of the thoracic wall. This study evaluated the outcome of Askin tumor in seven patients with an interdisciplinary approach. METHODS: Patients' records, treated between 1994 and 2011, were reviewed retrospectively. Seven patients (three male, four female; mean age 12.3 years; range 2-21 years) were included. All patients received neoadjuvant chemotherapy. After reduction of initial tumor volume, radical tumor resection and thoracic wall reconstruction were performed. All survivors were evaluated in 2011 by clinical examination and lung function test. RESULTS: Five-year survival rate in our group of patients is 86 % and overall survival is 71 %. There were two mortalities. One patient passed away 7.5 years after the primary management, mainly attributed to tumor progression, which demanded aggressive surgical procedures and irradiation. Another patient died 18 months after the first diagnosis after several surgical interventions for recurrent multiple pulmonary metastases. Three years after the first diagnosis, one patient suffered from clear cell sarcoma of the contralateral kidney and developed a local recurrence of Askin 1 year later. The large chest wall defects arising after surgery have been successfully reconstructed using combination of latissimus dorsi muscle flaps and biomaterials. CONCLUSION: Data of pediatric patients with Askin tumor is scarce. Analysis of our seven patient series indicates that improved outcomes (71 % over all survival rate and 86 % 5-year survival rate) can be achieved by aggressive interdisciplinary management including radical surgery and chemotherapy. Chest wall stability can be achieved by utilization of local muscle flaps and biomaterials to cover surgical chest wall defects.

Primitive neuroectodermal tumor of adrenal: clinical presentation and outcomes.

Primitive neuroectodermal tumor (PNET) of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm) on computed tomography (CT) was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE). This is the first report of adrenal peripheral PNET (pPNET) from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

Peripheral primitive neuroectodermal tumor of the pleura in a 41-year-old female.

Peripheral primitive neuroectodermal tumor (pPNET) is a rare, very aggressive neoplasm that belongs to a small round cell tumor, and most often arises from the chest wall. Here, we report a female case with proven pPNET who was treated in our institution. She presented with a history of left side chest pain, cough, and significant weight loss. Contrast enhanced CT imaging of the chest showed multiple left pleural-based enhancing masses with left diaphragmatic involvement. She underwent chemotherapy followed by tumor debulking through thoracotomy. However, she died of rapid growth from recurrent local tumors 3 months thereafter.

Primitive chest wall neuroectodermal tumor in a pediatric patient.

A 13-year-old boy with a primitive neuroectodermal tumor of the chest wall is presented. After four cycles of chemotherapy, a computed tomography scan of his chest showed a larger mass invading the left upper lobe of the lung. He underwent resection of the left chest wall from the left fourth to sixth ribs, including the tumor, combined with left upper lobectomy and lymph node dissection. A diagnosis of primitive neuroectodermal tumor was confirmed histopathologically and immunohistochemically. After surgery, four cycles of chemotherapy with ifosfamide and etoposide were given. One year after treatment, the patient is currently doing well without evidence of recurrence.

Giant extraosseous Ewing sarcoma of the lung in a young adolescent female--a case report.

Extraosseous Ewing sarcoma is a rare soft tissue tumour that is histologically indistinguishable from the bone Ewing sarcoma. The translocation involving chromosome 22 along with CD 99 expression is pathognomonic and is useful in differentiating from other small round cell tumours. Primary lung involvement by this malignant tumour is very uncommon and up to this date only ten cases have been reported. We report a further case in a 15 year-old-female who presented with a huge lung mass causing an opaque haemithorax.