Background-The long-term psychological impact of pediatric sarcoma is largely unknown. As part of a cross-sectional study examining the late effects of pediatric sarcoma therapy, we examined whether psychological distress or posttraumatic stress symptoms are present in an adult cohort of pediatric sarcoma survivors.

After a median follow up of 17 years, adult SARC survivors of MMT had an increased prevalence of MST, especially those less than 40 years old. The development of MST in this population was associated with decreased testosterone and activity levels.

Sarcoma survivors demonstrate diminished locoregional and global musculoskeletal functioning which likely limit occupational opportunities and socioeconomic health. In addition, the combination of diminished cardiac reserve, limited activity levels, and lipid dysregulation in sarcoma survivors suggests that this population is at increased risk for cardiovascular disease, even many years following completion of sarcoma therapy. Sarcoma survivors may benefit from life long follow-up for cardiovascular disease and from occupational counseling upon completion of therapy.

Nodular target lesions identified on MRI in individuals with NF1 and PN demonstrate increased FDG uptake similar to MPNST, but may be benign on biopsy. Nodular target lesions may be at greater risk for malignant transformation, but their biologic and clinical behavior has not been well studied. Careful longitudinal evaluation will be required to better understand the malignant potential of these lesions.

We describe the first pediatric case of clinical and biochemical improvement of paraneoplastic MTC-related Cushing syndrome after treatment with vandetanib. Vandetanib and possibly other tyrosine kinase inhibitors may be a novel beneficial option in patients with neuroendocrine tumor-related ectopic Cushing syndrome.

Background Spinal neurofibromas (SNF) in Neurofibromatosis type 1 (NF1) can cause progressive spinal cord compression and neurological dysfunction. The MEK inhibitor selumetinib shrinks the majority of plexiform neurofibromas (PN) in patients with NF1. We assessed the effect of selumetinib on SNF. Methods Pediatric and adult patients with NF1 and inoperable PN participating in phase 2 studies of selumetinib for PN were included in this analysis if they had SNF and serial spine MRIs. Selumetinib was administered orally at the recommended dose of 25 mg/m2/dose BID (max 50 mg BID) (1 cycle =28 days). We qualitatively assessed the effect of selumetinib on SNF-related spinal canal distortion, cerebrospinal fluid distribution and spinal cord deformity on MRI. Results Twenty-four patients (18 male), median age 16.9 years (range, 6.2-60.3) had SNF, 22 of which were associated with the same nerves as the target PN assessed on the clinical trial. Twenty patients had spinal cord deformity. Twenty-three patients completed at least 12 treatment cycles to date. Eighteen patients showed subtle to marked improvement in SNF burden, 5 remained stable, and no worsening was observed during treatment. Conclusions This is the first study describing the effect of selumetinib on SNF. Eighteen of 24 patients exhibited some improvement of SNF burden on imaging. These findings suggest that selumetinib may prevent the worsening of cord compression, potentially reducing the need for surgical interventions in select patients or benefitting patients who do not have a surgical option. Prospective evaluation of the clinical benefit of selumetinib for SNF is warranted.

Allogeneic stem cell transplantation (SCT) for solid tumors remains under investigation. We report a case of extended disease stability after a non-myeloablative peripheral blood SCT for metastatic, refractory Ewing sarcoma. Of note, the patient developed metastatic disease to two unusual sites -the brain and small intestine. The allogeneic SCT environment may alter typical metastatic patterns, and may represent an ideal platform to manipulate and enhance the anti-tumor immune response. Further clinical trials are needed to evaluate the role for allogeneic SCT for this disease.Current therapies for metastatic or relapsed Ewing sarcoma have not substantially improved outcomes in this high-risk population with five-year survival rates < 20% 1. Graft-versusmalignancy reactivity clearly contributes to the curative potential of allogeneic stem cell transplants (SCT) for leukemias and lymphomas, however the utility of allogeneic SCT for solid tumors remains controversial. Evidence for a graft-versus-tumor effect comes primarily from metastatic renal cell carcinoma 2, however responses have been reported in sarcomas, including a graft-versus-Ewing effect 3 -6. Here we report a case of disease stability followed by an unusual pattern of recurrence in a Ewing sarcoma patient following reduced intensity allogeneic SCT.A 26-year-old male initially presented with a 4-month history of left thigh pain and a palpable thigh mass. MRI revealed a 17 × 17cm mass arising from the left lateral femur, complicated by pathologic fracture. Needle biopsy revealed a Ewing sarcoma with no metastases noted on presentation. The patient received standard five-drug therapy (cyclophosphamide, doxorubicin and vincristine alternating with ifosfamide and etoposide) with local control consisting of 5580cGy radiation to the femur. At the completion of initial therapy there was no evidence of disease. One year later, a routine restaging chest CT revealed pulmonary metastasis and a left hilar lymph node ( Figure 1A). The remainder of restaging was negative including bone marrow biopsy. The patient received 4 cycles of cyclophosphamide and topotecan, during which time the pulmonary lesions progressed ( Figure 1B). He was then enrolled on an IRB-approved, reduced intensity, allogeneic SCT protocol for patients with ultra-high risk pediatric sarcomas. (etoposide, prednisone, vincristine, doxorubicin, cyclophosphamide) were given for immune depletion and disease control, during which the pulmonary disease was stable with no new lesions. His preparative chemotherapy prior to SCT comprised of fludarabine, cyclophosphamide and melphalan followed by infusion of unmanipulated, G-CSF mobilized peripheral blood stem cells from a fully matched sibling on day +0. GVHD prophylaxis consisted of cyclosporine monotherapy. Myeloid engraftment occurred on day +10 with full donor chimerism by day +14. On day +19 he developed biopsy-proven acute GVHD of the skin and liver. Methylprednisolone was initiated, cyclosporine was discontinued, and tacrolimus was start...

Background Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined the response rate to selumetinib in children with NF1 PN without clinically significant morbidity. Methods Children with NF1 and inoperable PNs, which were not yet causing clinically significant morbidity but had the potential to cause symptoms, received selumetinib at 25 mg/m2 orally twice daily (1 cycle = 28 days). Volumetric magnetic resonance imaging analysis and outcome assessments, including patient-reported (PRO), observer-reported, and functional outcome measures were performed every 4 cycles for 2 years, with changes assessed over time. A confirmed partial response (cPR) was defined as PN volume decrease of ≥20% on at least 2 consecutive scans ≥3 months apart. Results 72% of subjects experienced a cPR on selumetinib. Participants received selumetinib for a median of 41 cycles (min 2, max 67) at data cutoff. Approximately half of the children rated having some target tumor pain at baseline, which significantly decreased by pre-cycle 13. Most objectively measured baseline functions, including visual, motor, bowel/bladder, or airway function were within normal limits and did not clinically or statistically worsen during treatment. Conclusions Selumetinib resulted in PN shrinkage in most subjects with NF1 PN without clinically significant morbidity. No new PN-related symptoms developed while on selumetinib, and PRO measures indicated declines in tumor-related pain intensity. This supports that selumetinib treatment may prevent the development of PN-related morbidities, though future prospective studies are needed to confirm these results. Clinical Trial registration ClinicalTrials.gov NCT01362803.