Palliative sedation in paediatric solid tumour patients: choosing the best drugs.

OBJECTIVES: Cancer remains the leading cause of mortality by disease in childhood in high-income countries. For terminally ill children, care focuses on quality of life, and patient management fundamentally affects grieving families. This paper describes our experience of palliative sedation (PS) for children with refractory symptoms caused by solid tumours, focusing on the drugs involved. METHODS: We retrospectively collected data on all children treated for cancer who died at the pediatric oncology unit of the Fondazione IRCCS Istituto Nazionale dei Tumori between January 2016 and December 2020. RESULTS: Of the 29 patients eligible for the study, all but 4 received PS. Midazolam was always used, combined in 16 cases with other drugs (mainly classic neuroleptics, alpha-2 agonists and antihistamines). Throughout the period of PS and on the day of death, patients with sarcoma were given higher doses of midazolam and morphine, and more often received combinations of drugs than patients with brain tumours. Sarcoma causes significant symptoms, while brain tumours require less intensive analgesic-sedative therapies because they already impair a patient's state of consciousness. CONCLUSIONS: Optimising pharmacological treatments demands a medical team that knows how drugs (often developed for other indications) work. Emotional and relational aspects are important too, and any action to lower a patient's consciousness should be explained to the family and justified. Parents should not feel like helpless witnesses. Guidelines on PS in paediatrics could help, providing they acknowledge that a child's death is always a unique case.

Prolonged COVID-19 infection in a child with lymphoblastic non-Hodgkin lymphoma: which is the best management?

During the coronavirus disease 2019 (COVID-19) pandemic, oncologists have managed patients at higher risk of having a severe course of this infection. This raises new questions about their correct management, as well as the difficulty of distinguishing tumor/treatments complications from those related to COVID-19. We report a case of an 11-year-old boy undergoing treatment for T-cell lymphoblastic lymphoma who experienced a prolonged COVID-19 course. Oncologic therapy was continued without significant changes compared to the initially planned treatment. No relevant complications occurred. COVID-19 convalescent plasma was administered, resulting in a positive antibody titer after 24 days.

Children and adolescent solid tumours and high-intensity end-of-life care: what can be done to reduce acute care admissions?

Despite improvements in survival, cancer remains the leading cause of non-accidental death in children and adolescents, who risk receiving high-intensity end-of-life (HI-EOL) care. OBJECTIVE: To analyse treatments for relapses (particularly in the last weeks of life), assess their impact on the EOL, identify patients most likely to receive HI-EOL care and examine whether palliative care services can contain the intensity of EOL care. METHODS: This retrospective study involved patients treated at the paediatric oncology unit of the Istituto Nazionale Tumori in Milan who died between 2018 and 2020. The primary outcome was HI-EOL care, defined as: ≥1 session of intravenous chemotherapy <14 days before death; ≥1 hospitalisation in intensive care in the last 30 days of life and ≥1 emergency room admission in the last 30 days of life. RESULTS: The study concerned 68 patients, and 17 had HI-EOL care. Patients given specific in-hospital treatments in the last 14 days of their life more frequently died in hospital. Those given aggressive EOL care were less likely to die at home or in the hospice. Patients with central nervous system (CNS) tumours were more likely to have treatments requiring hospitalisation, and to receive HI-EOL care. CONCLUSION: These results underscore the importance of considering specific treatments at the EOL with caution. Treatments should be administered at home whenever possible.The early activation of palliative care, especially for fragile and complicated patients like those with CNS cancers, could help families cope with the many problems they face.

Age-appropriate multidisciplinary approach to young children with cancer undergoing radiotherapy: The SIESTA procedure.

A standardized multidisciplinary step-by-step approach to improve the compliance of young (or difficult) children having to undergo radiotherapy was described and applied. The procedure is called SIESTA, which stands for show-imagination-evaluation-support-treatment-anesthesia. Preliminary assessments suggest that the SIESTA approach was effective: the rate of young patients (≤6 years) requiring anesthesia decreased from 27% (14/52 cases) in 2011-2012 (before the procedure was adopted) to 13% (6/46) in 2018.

Stage 4 s neuroblastoma: features, management and outcome of 268 cases from the Italian Neuroblastoma Registry.

BACKGROUND: Infants diagnosed with stage 4 s neuroblastoma commonly experience spontaneous disease regression, with few succumbing without response to therapy. We analyzed a large cohort of such infants enrolled in the Italian Neuroblastoma Registry to detect changes over time in presenting features, treatment and outcome. METHODS: Of 3355 subjects aged 0-18 years with previously untreated neuroblastoma diagnosed between 1979 and 2013, a total of 280 infants (8.3%) had stage 4 s characteristics, 268 of whom were eligible for analyses. Three treatment eras were identified on the basis of based diagnostic and chemotherapy adopted. Group 1 patients received upfront chemotherapy; Group 2 and 3 patients underwent observation in the absence of life-threatening symptoms (LTS), except for Group 3 patients with amplified MYCN gene, who received more aggressive therapy. RESULTS: The three groups were comparable, with few exceptions. Ten-year overall survival significantly increased from 76.9 to 89.7% and was worse for male gender, age 0-29 days and presence of selected LTS on diagnosis, elevated LDH, and abnormal biologic features. Infants who underwent primary resection ± chemotherapy did significantly better. On multivariate analysis, treatment eras and the association of hepatomegaly to dyspnea were independently associated with worse outcome. CONCLUSIONS: Our data confirm that stage 4 s neuroblastoma is curable in nearly 90% of cases. Hepatomegaly associated to dyspnea was the most important independent risk factor. The cure rate could be further increased through timely identification of patients at risk who might benefit from surgical techniques, such as intra-arterial chemoembolization and/or liver transplantation, which must be carried out in institutions with specific expertise.

Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients.

BACKGROUND: Indirect evidence suggesting the immunosensitivity/immunogenicity of neuroblastoma is accumulating. The aims of this study were to investigate the immune landscape of neuroblastoma and to evaluate the in vivo immunogenicity of the NY-ESO-1 tumor antigen in advanced neuroblastoma patients. METHODS: The immune infiltrating cells of the NY-ESO-1+ tumors from three HLA*A201 patients with metastatic neuroblastoma who relapsed after conventional treatments were evaluated by immunohistochemistry. The patients were vaccinated with the HLA-A*0201-restricted peptide NY-ESO-1157-165(V). The peptide was emulsified in Montanide ISA51 and given subcutaneously in a phase I pilot study. The immunogenicity of NY-ESO-1 antigen was evaluated by monitoring mononuclear cells in patient peripheral blood, pre- and post-vaccine, by short-term in vitro sensitization, HLA-multimer staining and IFN-γ ELISpot analysis. RESULTS: Both CD3 T cells and CD163 myeloid cells were present in pre-vaccine tumors and PD-1 and PD-L1 expression was mainly found in the immune infiltrate. Despite the advanced stage of the disease, the vaccination induced systemic NY-ESO-1 specific CD8 T cells releasing IFN-γ in response to activation with the NY-ESO-1 peptide and an HLA-A2 positive neuroblastoma cell line. CONCLUSIONS: Our results indicate that vaccination with a tumor-associated peptide is able to boost NY-ESO-1-specific, functionally active T cells in advanced neuroblastoma patients with lymphocyte infiltration in their pre-vaccine tumors. TRIAL REGISTRATION: EudraCT #2006-002859-33.

Peripheral neuroblastic tumor of the kidney: case report and review of literature.

INTRODUCTION: Peripheral neuroblastic tumors (PNTs) account for 8%-10% of all pediatric tumors. Adrenal glands and sympathetic ganglia are the commonest site of tumor growth. In the clinicopathologic spectrum of PNTs, neuroblastoma and ganglioneuroma are the most primitive and the most mature tumor form, while ganglioneuroblastoma represents an intermediate state of maturation. Surgical resection is the therapy of choice in localized disease, but can lead to serious complications when performed in the presence of certain imaging-defined risk factors. CASE PRESENTATION: We present a rare case of primary intrarenal ganglioneuroblastoma diagnosed in a teenager who underwent conservative surgery and, despite this, developed upper pole renal ischemia without loss of parenchymal function. CONCLUSION: We underline the complex management of these extremely rare cases of neuroblastic tumors, which require a dedicated multidisciplinary team.

Thyroid carcinoma after treatment for malignancies in childhood and adolescence: from diagnosis through follow-up.

With improvements in the survival rates after childhood cancer, many clinicians have turned their attention to reporting on late effects, and how they might be prevented or treated. In childhood the thyroid gland is especially vulnerable to the carcinogenic action of ionizing radiation. This retrospective study focused on secondary thyroid cancers seen at our institution over more than 30 years (between 1980 and 2012) in patients treated for other malignancies in pediatric age. 36 patients were identified. In most cases, the primary cancer had been Hodgkin disease, and all the patients had been administered radiotherapy for their first malignancy. The secondary thyroid cancers were treated with total thyroidectomy in 27 cases (six with lymphadenectomy), and hemithyroidectomy in nine (one with lymphadenectomy). 12 Patients were also given radiometabolic therapy. All but two had TSH suppression therapy. The histological diagnoses were: 31 papillary and five follicular carcinomas. At 5 and 10 years, the OS was 100 and 95 %, respectively, and the PFS was 96 and 83 %. None of the patients died of their thyroid disease. Nodal involvement at onset was the only factor correlating with recurrence. Surgical sequelae only occurred in patients who underwent total thyroidectomy. Survival in these patients did not depend on the extent of surgery on the thyroid parenchyma. Our data confirm a good prognosis for secondary thyroid cancer, prompting us to encourage a minimalist approach to the treatment of these particular patients wherever possible.

Neuroblastoma in patients over 12 years old: a 20-year experience at the Istituto Nazionale Tumori of Milan.

AIMS AND BACKGROUND: Neuroblastoma is the most common solid extracranial tumor in children. The median age of onset is 2 years, with more than 95% of patients younger than 10 years at diagnosis. As neuroblastoma is rare in adolescents and exceedingly rare in adults, few series are reported in the literature. In the present study, we analyzed the outcomes and clinical characteristics of a mono-institutional series. METHODS: We describe 27 consecutive patients over 12 years of age (range, 12-69) with previously untreated neuroblastoma treated at our Institution between 1982 and 2001. RESULTS: Overall survival at 5 and 10 years was 40% and 20%, respectively, and progression-free survival at 5 and 10 years was 18%. In the present series, there was a long interval between the onset of signs/symptoms and diagnosis, and between recurrence/progression and death. None had MYCN amplification. CONCLUSIONS: The passive course of the disease in most of our patients did not reflect a more favorable outcome compared with younger patients, thus suggesting a possible genetically different subset of neuroblastoma in older patients.

End of life in children with cancer: experience at the pediatric oncology department of the istituto nazionale tumori in Milan.

BACKGROUND: Coping with end-stage pediatric cancer patients and the related bereavement is a challenge for all the caregivers involved. PROCEDURE: Forty-seven cancer patients who died in 2006 were assessed as concerns the main place of care in the end stage of their disease, their symptoms, the palliative treatments received, and the site of death. RESULTS: The end stage was managed at the Istituto Nazionale Tumori Pediatric Oncology Department in 61% of cases, at home in 26%, and in hospices or other hospital facilities in 11%. Pain was the most common symptom, followed by asthenia, anorexia, dyspnea, and nausea/vomiting. About half the patients died at home, 8.5% at our institute, 43% at other hospitals, and 8.5% in hospices. CONCLUSIONS: The care of pediatric cancer patients during the end stage of their disease is the responsibility of the caregivers who have followed them up since their diagnosis. However, it would be useful to establish an exchange of information and expertise between pediatric oncologists and the other facilities involved (hospices, other hospitals) or people assisting patients at home (family, family pediatrician/general practitioner GP).