Publications by authors named "M A Karajannis"
Background: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.
Methods: We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features.
Article Synopsis
- The study analyzed genetic alterations in cerebrospinal fluid (CSF) from 711 patients to help classify CNS cancers and guide targeted therapies.
- They found detectable circulating tumor DNA (ctDNA) in over half of CSF samples from patients with CNS tumors, while none was found in samples from patients without CNS tumors.
- The research also revealed clonal evolution and resistance mechanisms over time, with ctDNA presence linked to poorer overall survival rates for these patients.
Craniospinal irradiation and/or intraventricular radioimmunotherapy after high-dose chemotherapy and autologous stem cell rescue in patients with CNS retinoblastoma-Safety and outcomes.
Pediatr Blood Cancer
November 2024
Article Synopsis
- The prognosis for patients with central nervous system retinoblastoma (RB) after high-dose chemotherapy and stem cell transplant remains poor, and the effects of radiation therapy used afterward are unclear.
- A study reviewed data from 16 patients with CNS RB who received chemotherapy followed by high-dose stem cell transplant, observing a 75% response rate to initial treatment.
- Patients who received radiation therapy post-transplant had a 62.5% survival rate at 5 years, while those who did not only had a 28.6% survival rate, suggesting that radiation could improve outcomes and warrants further clinical trials.
Tumors develop in an oxidative environment characterized by peroxynitrite production and downstream protein tyrosine (Y) nitration. We showed that tyrosine nitration supports schwannoma cell proliferation and regulates cell metabolism in the inheritable tumor disorder NF2-related Schwannomatosis (NF2-SWN). Here, we identified the chaperone Heat shock protein 90 (Hsp90) as the first nitrated protein that acts as a metabolic switch to promote schwannoma cell proliferation.
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- Re-irradiation (reRT) for locally recurrent diffuse intrinsic pontine glioma (DIPG) shows promise for increasing survival, with the study exploring both conventional fractionation (CF) and hypofractionation (HF) techniques.
- The study reviewed data from 22 pediatric patients, highlighting that patients receiving HF had a median overall survival of 8.2 months compared to 7.5 months for CF, although the difference wasn’t statistically significant.
- Results showed significant clinical improvement with many patients able to reduce steroid use post-treatment, and no cases of radionecrosis were reported, suggesting HF could be an effective alternative for symptom management.