Christine Chordas

A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer.

Standard chemotherapeutic drugs, when modified by the frequency and dose of administration, can target angiogenesis. This approach is referred to as antiangiogenic chemotherapy, low-dose chemotherapy, or metronomic chemotherapy. This study evaluated the feasibility of 6 months of metronomic chemotherapy, its toxicity and tolerability, surrogate markers of activity, and preliminary evidence of activity in children with recurrent or progressive cancer. Twenty consecutive children were enrolled and received continuous oral thalidomide and celecoxib with alternating oral etoposide and cyclophosphamide every 21 days for a planned duration of 6 months using antiangiogenic doses of all four drugs. Surrogate markers including bFGF, VEGF, endostatin, and thrombospondin were also evaluated. Therapy was well tolerated in this heavily pretreated population. Toxicities (predominantly reversible bone marrow suppression) responded to dose modifications. Sixty percent of the patients received less than the prescribed 6 months of therapy due to toxicity (one case of deep vein thrombosis), personal choice (1 patient), or disease progression (10 patients). Forty percent of the patients completed the 6 months of therapy, resulting in prolonged or persistent disease-free status. One quarter of all patients continue to be progression free more than 123 weeks from starting therapy. Sixteen percent of patients showed a radiographic partial response. Only elevated thrombospondin-1 levels appeared to correlate with prolonged response. This oral antiangiogenic chemotherapy regimen was well tolerated in this heavily pretreated pediatric population, which showed prolonged or persistent disease-free status, supporting the continued study of antiangiogenic/metronomic chemotherapy in human clinical trials.

Late effects of therapy for pediatric brain tumor survivors.

Approximately 2 of every 3 of all pediatric patients with brain tumors will be long-term survivors. However, there is a steep cost for pediatric brain tumor survivors, and the group as a whole faces significantly more late effects than many other survivors of pediatric cancers. Most of these effects can be attributed to direct neurologic damage to the developing brain caused by the tumor and its removal, the long-term toxicity of chemotherapy, or the effects of irradiation on the central nervous system. The late effects experienced by childhood brain tumor survivors involve multiple domains. This article will review the significant late effects that occur within the medical, neurocognitive, psychosocial, and economic domains of the survivorship experience. We conclude by discussing how the late effects in different domains often coexist and can create a complex set of obstacles that pose significant challenges for a survivor of a pediatric brain tumor on a daily basis.

Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor

AbstractAtypical teratoid/rhabdoid tumors (AT/RT) are highly malignant lesions of childhood that carry a very poor prognosis. AT/RT can occur in the central nervous system (CNS AT/RT) and disease in this location carries an even worse prognosis with a median survival of 7 months. In spite of multiple treatment regimens consisting of maximal surgical resection (including second look surgery), radiation therapy (focal and craniospinal), and multi-agent intravenous, oral and intrathecal chemotherapy, with or without high-dose therapy and stem cell rescue, only seven long-term survivors of CNS AT/RT have been reported, all in patients with newly diagnosed disease. For this reason, many centers now direct such patients, particularly those under 5 years of age, or those with recurrent disease, towards comfort care rather than attempt curative therapy. We now report on four children, two with newly diagnosed CNS AT/RT and two with progressive disease after multi-agent chemotherapy who are long term survivors (median follow-up of 37 months) using a combination of surgery, radiation therapy, and intensive chemotherapy. The chemotherapy component was modified from the Intergroup Rhabdomyosarcoma Study Group (IRS III) parameningeal protocol as three of the seven reported survivors in the literature were treated using this type of therapy. Our four patients, when added to the three reported survivors in the literature using this approach, suggest that patients provided this aggressive therapy can significantly alter the course of their disease. More importantly, we report on the first two survivors after relapse with multi-agent intravenous and intrathecal chemotherapy treated with this modified regimen.

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer

Preclinical models show that an antiangiogenic regimen at low‐dose daily (metronomic) dosing may be effective against chemotherapy‐resistant tumors. We undertook a prospective, open‐label, single‐arm, multi‐institutional phase II study to evaluate the efficacy of a “5‐drug” oral regimen in children with recurrent or progressive cancer.

Medical, psychological, cognitive and educational late-effects in pediatric low-grade glioma survivors treated with surgery only†

Surgical resection is often the only treatment necessary for pediatric low‐grade gliomas (LGGs) and is thought to define a population with an excellent long‐term prognosis. The goal of this study was to describe the multidimensional late‐effects of pediatric LGG survivors treated exclusively with surgery.

Screening for pain in pediatric brain tumor survivors using the pain thermometer.

Numerous instruments have been developed to measure pain within various populations; however, there remains limited understanding of how these tools are applicable to childhood cancer survivors. This study compared a single-item screening measure, the Pain Thermometer (PT), with a more in-depth measure, the Brief Pain Survey (BPS), in a cohort of childhood brain tumor survivors. Ninety-nine survivors (aged 13-32 years) with a median time from diagnosis of 9.9 years (range = 2-18 years) completed the 2 instruments. Thirty-seven survivors (37.4%) were identified on the BPS as having clinically significant pain, but the PT was not found to be an accurate tool for identifying these pain cases. Application of receiver operating characteristic curve analysis of PT ratings against BPS criterion indicated overall concordance between measures. No cutoff score on the PT were identified that resulted in acceptable sensitivity, meaning pain cases identified on the BPS would be missed on the PT. Findings suggest that a multi-item screening measure may better identify clinically significant pain in childhood brain tumor survivors compared with a 1-item screening measure alone.

A social program for adolescent and young adult survivors of pediatric brain tumors: The power of a shared medical experience

ABSTRACT Survivors of pediatric brain tumors experience several medical and psychosocial late effects including deficits in social competence. This mixed methods study investigated the experience of 19 adolescent and young adult survivors of pediatric brain tumors and 17 parents who participated in a social support program. Qualitative results demonstrated a significant social isolation that was compounded by medical late effects. Survivors perceived social support and acceptance from interactions with peers who have similar medical backgrounds as a key aspect of the group experience. Parents reported increased social confidence among survivors, although they did not report that social gains generalized beyond the group setting. Interventions to promote the transfer of specific social skills are needed.

Recurrent ascites in a patient with low-grade astrocytoma and ventriculo-peritoneal shunt treated with the multikinase inhibitor sorafenib.

This report describes a 6-year-old boy with disseminated low-grade astrocytoma and ventriculo-peritoneal shunt, who developed recurrent ascites while receiving sorafenib on a clinical trial. Laboratory analysis of the peritoneal fluid showed no elevation of protein content and no evidence of underlying infection or tumor dissemination. This report highlights ascites as a previously unrecognized adverse reaction to sorafenib in a patient with a ventriculo-peritoneal shunt. We conclude that such patients should be closely monitored for this complication when treated with sorafenib.

Metachronous mediastinal seminoma occurring after intracranial germinoma in an adolescent.

We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-year-old boy with headaches and visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2 years later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.

A prospective, blinded analysis of A-PROTEIN (recoverin or CAR protein) levels in pediatric patients with central nervous system tumors

Abnormal expression of A‐PROTEIN has been identified in a number of tumors including carcinoma of the lung, breast, colon, prostate, and cervix. Brain tumors have been reported to express high plasma levels of A‐PROTEIN, suggesting that it may be of significant diagnostic and prognostic value.