Hypofractionated Palliative Radiotherapy for Relapsed and Refractory High-Risk Neuroblastoma.

While palliative radiotherapy (RT) is frequently used in the management of relapsed/refractory high-risk neuroblastoma (HR-NBL); outcomes after palliative hypofractionated RT (hypo-RT) remain poorly characterized. : We conducted a multi-institutional retrospective study of 38 patients who were diagnosed with HR-NBL between 1997 and 2021 and received palliative RT. Conventional RT (conv-RT) and hypo-RT were defined as palliative treatment courses using dose ≤2 or >2 Gy per fraction, respectively.

A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma.

Background: This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.

Methods: Patients aged 2-21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

Background: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields.

Methods: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis.

Factors influencing parents' choice of palliative treatment goals for children with relapsed or refractory neuroblastoma: A multi-site longitudinal survey study.

Background: Many parents of children with advanced cancer report curative goals and continue intensive therapies that can compound symptoms and suffering. Factors that influence parents to choose palliation as the primary treatment goal are not well understood. The objective of this study was to examine experiences impacting parents' report of palliative goals adjusted for time.

STK11 Adnexal Tumor in an Adolescent Female: Diagnostic Pitfalls of a Recently Described Entity.

STK11 adnexal tumor is a recently described entity with less than 25 cases reported to date. These aggressive tumors typically occur in paratubal/paraovarian soft tissues, have characteristically striking morphologic and immunohistochemical heterogeneity, and harbor pathognomonic alterations in . These occur almost exclusively in adult patients, with only one reported in a pediatric patient (to our knowledge).

A single-institution pediatric and young adult interventional oncology collaborative: Novel therapeutic options for relapsed/refractory solid tumors.

Background: Pediatric interventional oncology (PIO) is a growing field intended to provide additional or alternative treatment options for pediatric patients with benign or malignant tumors. Large series of patients treated uniformly and subjected to rigorous endpoints for efficacy are not available.

Methods: We designed a collaborative initiative to capture data from pediatric patients with benign and malignant tumors who underwent a therapeutic interventional radiology procedure.

Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.

Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years).

Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor.

Purpose: Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy.

Patients And Methods: Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded.

Efficacy of post-induction therapy for high-risk neuroblastoma patients with end-induction residual disease.

Background: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving the response before autologous stem cell transplantation (ASCT). The authors conducted a multicenter, retrospective study to investigate the efficacy of this approach.

Methods: Patients diagnosed between 2008 and 2018 without progressive disease with a partial response or worse at end-induction were stratified according to the post-induction treatment: 1) no additional therapy before ASCT (cohort 1), 2) post-induction "bridge" therapy before ASCT (cohort 2), and 3) post-induction therapy without ASCT (cohort 3).

Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG).

Background: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.

Methods: STARTRK-NG (NCT02650401) is a phase 1/2 trial.

Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors.

Background: Sorafenib,an orally bioavailable, multitarget tyrosine kinase inhibitor, and irinotecan, a topoisomerase I inhibitor, have demonstrated activity in pediatric and adult malignancies. We evaluated the toxicity, pharmacokinetic (PK), and pharmacogenomic (PGX) profile of sorafenib with irinotecan in children with relapsed or refractory solid tumors and assessed the feasibility of incorporating patient-reported outcome (PRO) measures as an adjunct to traditional endpoints.

Methods: Sorafenib, continuous oral twice daily dosing, was administered with irinotecan, orally, once daily days 1-5, repeated every 21 days (NCT01518413).

Randomized Phase II Trial of MIBG Versus MIBG, Vincristine, and Irinotecan Versus MIBG and Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A Report From NANT Consortium.

Purpose: I-metaiodobenzylguanidine (MIBG) is an active radiotherapeutic for neuroblastoma. The primary aim of this trial was to identify which of three MIBG regimens was likely associated with the highest true response rate.

Patients And Methods: Patients 1-30 years were eligible if they had relapsed or refractory neuroblastoma, at least one MIBG-avid site, and adequate autologous stem cells.

Retrospective evaluation of single patient investigational new drug (IND) requests in pediatric oncology.

Background: Single patient Investigational New Drug (IND) applications are one mechanism through which experimental therapies are accessed for children with cancer. The landscape of use, outcomes, and toxicity from single patient INDs remains unknown in pediatric oncology.

Methods: We performed a retrospective analysis of all single patient INDs requested and prescribed at a single institution between 1/1/2007 and 5/1/2019.

Facial Paralysis From Post-transplant Lymphoproliferative Disorder.

Objective: We report a case of facial paresis and profound hearing loss from post-transplant lymphoproliferative disorder (PTLD) in a pediatric patient with neuroblastoma.

Patient: Three-year-old boy with rapidly progressive right facial paresis and sensorineural hearing loss. High-risk neuroblastoma had been diagnosed 1 year earlier, treated with chemotherapy and resection of the adrenal primary tumor.

The use of interval-compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare aggressive sarcoma that affects children and young adults, and portends poor outcomes despite intensive multimodal treatment approaches. We report toxicity, response, and outcomes of patients with DSRCT treated with the addition of vincristine, irinotecan, and temozolomide (VIT) to interval-compressed chemotherapy as per Children's Oncology Group ARST08P1.

Methods: All newly diagnosed pediatric patients with DSRCT treated at Dana-Farber Cancer Institute and Boston Children's Hospital between 2014 and 2019 as per ARST08P1, Arm P2 with replacement of VAC cycles with VIT, were identified.

Racial and Ethnic Differences in Communication and Care for Children With Advanced Cancer.

Context: Racial and ethnic disparities in end-of-life care are well documented among adults with advanced cancer.

Objectives: To examine the extent to which communication and care differ by race and ethnicity among children with advanced cancer.

Methods: We conducted a prospective cohort study at nine pediatric cancer centers enrolling 95 parents (42% racial/ethnic minorities) of children with poor prognosis cancer (relapsed/refractory high-risk neuroblastoma).

A Novel Fusion in Pediatric Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is most commonly associated with gene mutations. fusions have rarely been described, although not previously in pediatrics and not previously partnered with in MTC or any other cancer. A 10-year-old boy with progressive stridor was found to have metastatic MTC, including lung, lymph node, and adrenal metastases.

Unrealistic parental expectations for cure in poor-prognosis childhood cancer.

Background: Many parents of children with advanced cancer pursue curative goals when cure is no longer possible. To the authors' knowledge, no pediatric studies to date have prospectively evaluated prognosis communication or influences on decision making in poor-prognosis childhood cancer.

Methods: The authors conducted a prospective cohort study at 9 pediatric cancer centers that enrolled 95 parents of children with recurrent or refractory, high-risk neuroblastoma (63% of those who were approached), a condition for which cure rarely is achieved.

Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF and Isotretinoin in Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Phase II Study.

Purpose: Combining anti-GD2 (disialoganglioside) mAb with GM-CSF, IL2, and isotretinoin is now FDA-approved for high-risk neuroblastoma minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in neuroblastoma and is more effective in neuroblastoma-bearing mice than antibody and cytokine given separately.

Evaluation of the utility of Tc-MDP bone scintigraphy versus MIBG scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.

Purpose: Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma.

Methods: A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging.

Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study.

Importance: Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit.

Objective: To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors.

A phase I trial combining decitabine/dendritic cell vaccine targeting MAGE-A1, MAGE-A3 and NY-ESO-1 for children with relapsed or therapy-refractory neuroblastoma and sarcoma.

Antigen-specific immunotherapy was studied in a multi-institutional phase 1/2 study by combining decitabine (DAC) followed by an autologous dendritic cell (DC)/MAGE-A1, MAGE-A3 and NY-ESO-1 peptide vaccine in children with relapsed/refractory solid tumors. Patients aged 2.5-15 years with relapsed neuroblastoma, Ewing's sarcoma, osteosarcoma and rhabdomyosarcoma were eligible to receive DAC followed by DC pulsed with overlapping peptides derived from full-length MAGE-A1, MAGE-A3 and NY-ESO-1.