Rapid and Complete Response to Combination Anti-CTLA-4 and Anti-PD-1 Checkpoint Inhibitor Therapy in a Patient With Stage IV Refractory End-stage Epithelioid Sarcoma: A Case Report.

Epithelioid sarcoma, in the relapse-refractory setting, has limited expected survival. SMARCB1 inactivation, common in epithelioid sarcoma, causes loss of INI1 protein expression and overexpression of the cancer cell growth promoting methyltransferase enzyme, EZH2. We treated a 19-year-old male with stage IV SMARCB1 inactivated epithelioid sarcoma presenting with recurrent end stage (Eastern Cooperative Oncology Group Performance Status 4) rapidly progressing bulky disease with combination ipilimumab and nivolumab. He failed standard therapy and an EZH2 inhibitor (tazemetostat). He presented (May 13, 2019) with a large (16.1×18.6 cm) soft tissue back mass extending from T10 to L3. Complete clinical regression of the back mass occurred within 2 weeks (May 28, 2019) of cycle 1 of combined checkpoint inhibition therapy followed by a positron emission tomography-negative complete remission (October 11, 2019). After a second negative positron emission tomography/computed tomography scan (January 13, 2020), checkpoint inhibition therapy was discontinued. He has returned to normal activities with a normal physical examination and Eastern Cooperative Oncology Group Performance Status of 0 at his last visit (June 29, 2020). In conclusion, combined checkpoint inhibition therapy warrants further study in the salvage setting in patients with epithelioid and other INI1 protein-deficient sarcomas seemingly regardless of prior therapy, extent of disease, and performance status.

Stage IV Neuroblastoma with Metastatic Spread to the Mandible in a Young Child: Case Report and Review of the Literature.

BACKGROUND: Infants and young children with neuroblastoma (NB) may present with metastases. The primary tumor most commonly originates in the abdomen and metastasizes to lymph nodes, liver, and bone marrow. Infants and young children presenting with multiple skull metastases are rare. METHODS: We present a rare case of a 20-month-old child who presented with metastatic neuroblastoma and multiple skull lesions. The child responded well to induction chemotherapy followed by myeloablative busulfan/melphalan consolidation. RESULTS: The child had substantial tumor reduction after chemotherapy was started. There was a significant decrease in tumor sizes and uptake, as seen in the metaiodobenzylguanidine study. The 6-month follow-up examination showed complete remission, and the remission continues. CONCLUSIONS: Infants and young children with neuroblastoma rarely present with metastatic lesions to the skull. Even large lesions involving the skull base may be successfully treated with chemotherapy. The use of myeloablative busulfan/melphalan consolidation after induction chemotherapy can decrease the overall metastatic tumor burden. Craniofacial specialists should be aware of treatment options for these young children.

Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience.

BACKGROUND: Children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNET) have poor outcomes compared to medulloblastoma patients, despite similar treatments. In an effort to improve overall survival (OS) and event-free survival (EFS) and to decrease radiation exposure, the Head Start (HS) protocols treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy (ICHT) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR). PROCEDURES: Between 1991 and 2002, 43 children with sPNET were prospectively treated on two serial studies (HS I and II). After maximal safe surgical resection, patients on HS I and patients with localized disease on HS II were treated with five cycles of ICHT (vincristine, cisplatin, cyclophosphamide, and etoposide). Patients on HS II with disseminated disease received high-dose methotrexate during ICHT. If the disease remained stable or in response, patients received a single cycle of high-dose myeloablative chemotherapy followed by AuHCR. RESULTS: Five-year EFS and OS were 39% (95%CI: 24%, 53%) and 49 (95%CI: 33%, 62%), respectively. Non-pineal sPNET patients faired significantly better than those patients with pineal sPNETs. Metastasis at diagnosis, age, and extent of resection were not significant prognostic factors. Sixty percent of survivors (12 of 20) are alive without exposure to radiation therapy. CONCLUSIONS: ICHT followed by AuHCR in young patients with newly diagnosed sPNET appears to not only provide an improved EFS and OS for patients who typically have a poor prognosis, but also it successfully permitted deferral and elimination of radiation therapy in a significant proportion of patients.

Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors.

PURPOSE: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs). PATIENTS AND METHODS: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR. RESULTS: Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC. CONCLUSION: Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.

Human granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia: a Children's Cancer Group Study.

PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic toxicities, supportive care requirements, time to complete intensive therapy, and event-free survival (EFS) and overall survival (OS) in children with high-risk acute lymphoblastic leukemia (HR-ALL). PATIENTS AND METHODS: A total of 287 children with HR-ALL were randomly assigned to intensive chemotherapy regimens (New York I [NY I] or NY II) as part of the Children's Cancer Group (CCG)-1901 protocol. The induction phases consisted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide). Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation. Patients were randomly assigned to receive G-CSF (5 microg/kg/day) during either induction or initial consolidation. A crossover study analysis was done on the 259 patients who completed both phases of therapy. RESULTS: The mean time to neutrophil recovery (>/= 0.5 x 109/L) was reduced with G-CSF (16.7 v 19.1 days, P =.0003); however, patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia (149 v 164, P =.41), positive blood cultures (57 v 61, P =.66), or serious infections (75 v 79, P =.62). Hospitalization (14.0 v 13.9 days, P =.87) and induction therapy completion times (NY I, 30.3 v 31.3 days, P =.11; NY II, 33.4 v 32.3 days, P =.40) were not significantly altered. There were no differences in 6-year EFS (P =.24) or OS (P =.54) between patients receiving or not receiving G-CSF on CCG-1901, NY I and NY II. CONCLUSION: Children with high-risk ALL do not appear to benefit from prophylactic G-CSF.

Development of a software package for electronic documentation of orthopaedic x-ray findings.

Proper documentation of x-ray findings, including anatomical location, joint position, arthritis location with severity, fracture patterns, bone changes,changes from joint arthroplasty, and ICD-9 coding,are a vital aspect of the orthopedic surgeons' daily office task. While radiology software is available for certain templated studies, there is little in the way of orthopaedic electronic documentation other than templated "pick-lists" for common findings. The authors developed a software package with line drawings of a selected anatomical area that are color coded to divide individual bones into proximal interarticular,distal inter-articular, and shaft fractures. Each color coded section of a bone details both fracture patterns and bone changes possible for that area of the bone or joint. When a cursor is moved over each section of the bone, the various fracture patterns and bone changes then appear on the screen. The chosen fracture pattern, along with its associated description, is then electronically recorded coupled with its ICD-9 code including the specific digit when appropriate.