Erlotinib Therapy For Recurrent Respiratory Paillomatosis And Extralaryngeal Spread In Pediatrics

Background: Recurrent respiratory papillomatosis (RRP) can be a potentially life-threatening condition and a treatment challenge. Local therapies are associated with significant scarring and detrimental effects on voice and respiratory status. EGFR inhibitors have been reported to be an effective adjunctive therapy in patients with RRP. Objective: To report our institutional experience with Erlotinib in two pediatric patients with severe RRP. Method: Retrospective chart review of 2 pediatric patients with severe RRP. Results: Patient 1 is a 19y/o female who was referred to us at the age of 11. Patient was diagnosed with respiratory papillomatosis at birth. Since age 1.5yrs, she had been undergoing micro-laryngoscopy, bronchoscopy with laser or surgical excision of the lesions, on a 1-2 monthly basis. On examination she had no skin lesions. Her voice was only a whisper. No difficulty breathing or stridor. She was pre-pubertal. Endoscopic exam 3 weeks prior to starting therapy showed severely scarred larynx, no obvious laryngeal disease, diffuse subglottic and tracheal papillomatosis with extension into the left main bronchus. Biopsy of the lesion showed squamous papilloma, EGFR positive. Patient 2 is 14y/o who was referred to us at age 12. Patient was diagnosed at 5 months with respiratory papillomatosis of the larynx undergoing micro-laryngoscopy, bronchoscopy with laser or surgical excision of the lesions, on a 1-2 monthly basis. He developed respiratory distress post laryngoscopy and found to have 3 pulmonary lesions confirmed as papillomatosis post thoracotomy with wedge resections. Both patients were started on an EGFR inhibitor, Erlotinib at a dose of 85mg/m2 daily and DIM (diindolylmethane) 150mg twice daily. The skin care regimen included regular moisturizers and sunscreen; topical steroids and antibiotics as needed. Therapy was well tolerated except for grade 1 skin rash in both patients and grade 1 diarrhea as well, in Patient 1. For patient 1, within a month of therapy there was significant decrease in the lesions and by 6mo complete resolution of papillomatosis. She had 15mo of therapy. She is in remission 6 years off therapy. For patient 2, there has been decrease in lesions and the interval between laryngoscopy since start of therapy. CTs of chest confirm no recurrence of pulmonary lesions since starting Erlotinib. Conclusion: Erlotinib demonstrates efficacy in respiratory papillomatosis in children and may be considered as adjunct therapy with surgical excision in this disease. DIM is an aromatase inhibitor that potentiates the effect of Erlotinib

Eutectic mixture of lidocaine and prilocaine versus 1% lidocaine injection for lumbar punctures in pediatric oncology patients.

BACKGROUND: The role of local analgesics for lumbar punctures (LPs) in pediatric oncology patients has not been specifically studied. AIM: To compare the efficacy of eutectic mixture of local anesthetics (EMLA) cream to 1% lidocaine injection for LPs. METHOD: This was a retrospective observational study of all patients receiving either EMLA cream (EMLA group) or 1% lidocaine subcutaneous injection (lidocaine group) in addition to fentanyl and propofol for LPs over 18 months. Demographics, vital parameters, procedural and recovery times, propofol and fentanyl doses, and adverse events were studied. RESULTS: Two hundred ninety LPs in 49 children were studied: 148 in the EMLA group and 142 in the lidocaine group. There was no difference in demographics or preprocedural parameters between the two groups. LPs in the EMLA group were completed in a shorter time (7.5 minutes [CI 7.0-8.1] vs 9.4 minutes [CI 8.9-9.9]) with a faster recovery time (38.7 minutes [CI 36.9-40.9] vs 43.9 minutes. [CI 41.9-45.9]) as compared with the lidocaine group (P \u3c 0.001). The EMLA group required less maintenance doses (0.54 mg/kg [CI 0.47-0.62] vs 1.14 mg/kg [CI 1.06-1.21]) and total doses (2.58 mg/kg [CI 2.42-2.75] vs 3.12 mg/kg [CI 2.95-3.29]) of propofol as compared with the lidocaine group (P \u3c 0.0001). Adverse events in the EMLA group were less (19% vs 41%) as compared with the lidocaine group (P \u3c 0.0001). CONCLUSION: The addition of EMLA cream for procedural sedation for LPs in pediatric oncology patients significantly improves pain management in comparison with 1% lidocaine injection

Associations among diffusion tensor imaging and neurocognitive function in survivors of pediatric brain tumor: A pilot study.

The purpose of this study was to determine associations among neurocognitive outcomes and white matter integrity in the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and genu of the corpus callosum (gCC) in survivors of pediatric brain tumor and healthy controls (HCs). Eleven survivors (ages 8-16; \u3e2 years post-treatment) and 14 HCs underwent MRI; diffusion tensor imaging tractography (DSI Studio) was used to assess white matter integrity. Participants completed neuropsychological assessment of overall cognitive ability, executive function, processing speed, divided attention, and memory. As previously reported, survivors performed significantly worse than HCs on measures of overall IQ, working memory, processing speed, and executive function

Fronto-limbic white matter microstructure, behavior, and emotion regulation in survivors of pediatric brain tumor.

PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children\u27s emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type

Dynamic re-immunization of off-treatment childhood cancer survivors: An implementation feasibility study.

There are no universally approved re-vaccination guidelines for non-transplant pediatric cancer survivors. We hypothesized that by utilizing a response-based re-vaccination schedule, we could tailor vaccine schedules in off-treatment cancer survivors. Pre-vaccination antibody levels were obtained in 7 patients at an average of 20 days after the end of treatment date. In those without protective antibody levels, we administered vaccines 3 months after completion of treatment. Revaccinating patients 3 months after the end of treatment date resulted in protective antibody levels for most vaccines. We showed, on a preliminary basis, that vaccinating non-transplanted pediatric cancer survivors can be dynamically implemented in children with recovering immune function

Dynamic re-immunization of off-treatment childhood cancer survivors: An implementation feasibility study.

There are no universally approved re-vaccination guidelines for non-transplant pediatric cancer survivors. We hypothesized that by utilizing a response-based re-vaccination schedule, we could tailor vaccine schedules in off-treatment cancer survivors. Pre-vaccination antibody levels were obtained in 7 patients at an average of 20 days after the end of treatment date. In those without protective antibody levels, we administered vaccines 3 months after completion of treatment. Revaccinating patients 3 months after the end of treatment date resulted in protective antibody levels for most vaccines. We showed, on a preliminary basis, that vaccinating non-transplanted pediatric cancer survivors can be dynamically implemented in children with recovering immune function

Results of pre-diagnosis vaccination status, post-treatment IgG levels, and post-vaccine IgG levels.

<p>Results of pre-diagnosis vaccination status, post-treatment IgG levels, and post-vaccine IgG levels.</p