Joseph Gerald Pressey

Severe cytokine release syndrome in a patient receiving PD‐1‐directed therapy

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T‐cell engaging immunotherapy. Checkpoint blockade using anti‐programmed cell death 1 (anti‐PD‐1) inhibitors is an approach to antitumor immune system stimulation. A 29‐year‐old female with alveolar soft part sarcoma developed severe CRS after treatment with anti‐PD‐1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin‐6 inhibitor tocilizumab and corticosteroids.

Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes

Many patients with histiocytic disorders such as Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) have treatment-refractory disease or suffer recurrences. Recent findings of gene mutations in histiocytoses have generated options for targeted therapies. We sought to determine the utility of prospective sequencing of select genes to further characterize mutations and identify targeted therapies for patients with histiocytoses. Biopsies of 72 patients with a variety of histiocytoses underwent comprehensive genomic profiling with targeted DNA and RNA sequencing. Fifteen patients (21%) carried the known BRAF V600E mutation, and 11 patients (15%) carried various mutations in MAP2K1, which we confirm induce constitutive activation of extracellular signal-regulated kinase (ERK) and were sensitive to inhibitors of mitogen-activated protein kinase kinase (MEK, the product of MAP2K1). We also identified recurring ALK rearrangements, and 4 LCH patients with an uncommon in-frame deletion in BRAF (N486_P490del or N486_T491>K), resulting in constitutive activation of ERK with resistance to V600E-specific inhibitors. We subsequently describe clinical cases where patients with aggressive multisystem LCH experience dramatic and sustained responses to monotherapy with either dabrafenib or trametinib. These findings support our conclusion that comprehensive genomic profiling should be regularly applied to these disorders at diagnosis, and can positively impact clinical care.

Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging—A prospective trial

Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single‐photon emission computed tomography/computed tomography (SPECT‐CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET‐CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT‐CT with PET‐CT for the identification of nodal metastases in pediatric and AYA patients.

Surgical management and surveillance of pediatric appendiceal carcinoid tumor

PURPOSE Appendiceal carcinoid tumors are rare neuroendocrine neoplasms. The aim of this study was to determine if postoperative oncologic follow-up was necessary for this tumor. METHODS A retrospective review was performed of patients with appendiceal carcinoid 2000-2015. RESULTS 8382 patients underwent appendectomy 2000-2015. 30 (0.3%) had appendiceal carcinoid. 70% were female (n=21) with an average age of 13.5±2.8 years (range 8-18). Most presented with abdominal pain (n=29, 97%). 20% (n=6) had appendiceal perforation. Mean tumor size was 5.4±4mm (range microscopic - 15mm) with most at the appendiceal tip (n=18, 60%). No node infiltration was found, although 10% (n=3) had perineural and 3% (n=1) had lymphovascular invasion. Five were transmural (17%). Most patients were referred to oncology (n=19, 63%) for staging and surveillance including ultrasonography (n=11, 65%), MRI (n=7, 41%), and CT (n=6, 35%). The majority (79%, n=15) underwent serial 5-HIAA testing. All surveillance was found to be normal, and no patients required further treatment. Mean follow-up was 36±34 months, with 58% (n=11) continuing surveillance. Medical charges ranged

Pazopanib therapy for desmoid tumors in adolescent and young adult patients

8500-

A phase II, multicenter study of the EZH2 inhibitor tazemetostat in adult subjects with INI1-negative tumors or relapsed/refractory synovial sarcoma.

44,000. No recurrences have been identified. CONCLUSION Appendectomy is an adequate treatment for pediatric appendiceal carcinoid <16 mm despite presence of histological risk factors. More aggressive surgery and extensive oncologic follow up are of limited value. LEVEL OF EVIDENCE III. TYPE OF STUDY Retrospective comparative study.

Clinicopathologic Features of a Series of Primary Renal CIC-rearranged Sarcomas With Comprehensive Molecular Analysis

Desmoid tumors/aggressive fibromatosis (DT/AF) lack a reliably effective medical therapy. Surgical resection may be morbid and does not preclude recurrence. Radiation may carry severe late effects, particularly detrimental in young patients. At our institution, we recently observed promising results with pazopanib therapy for DT/AF in adolescent and young adult (AYA) patients.