Neonatal outcomes and follow-up of children born to women with pregnancy-associated cancer: a prospective observational study.

BACKGROUND: During the last decade, there has been a growing number of cases of children born from pregnancy-associated cancer (PAC), however there are currently insufficient data on the follow up to be observed in this category of newborns. Objective of the study was to evaluate the neonatal outcomes of infants born to mother with PAC, the potential adverse effect of chemotherapy during pregnancy and the risk of metastasis to the fetus. METHODS: Maternal clinical data and neonatal outcomes of child born to mothers diagnosed with PAC were collected; infants were divided into those were and were not exposed to chemotherapy during fetal life and their outcomes were compered. RESULTS: A total of 37 newborn infants from 36 women with PAC were analyzed. Preterm delivery occurred in 83.8% of the cases. No significant differences in neonatal outcomes were found between infants who were and were not exposed to chemotherapy during pregnancy. The median follow-up period was 12 months. CONCLUSIONS: PAC treatment during the second or third trimester does not seem to be dangerous for the fetus, however infants born from PAC must be carefully evaluated for to rule out the consequences of chemotherapy and exclude the presence of metastasis. Long-term follow-up, especially in children exposed to chemotherapy, should be encouraged to obtain relevant data on long-term toxicity.

Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers.

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood-brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail.

Stereotactic body radiotherapy for pulmonary oligometastases: a monoinstitutional analysis of clinical outcomes and potential prognostic factors.

PURPOSE: We report the retrospective data of a cohort of patients who received stereotactic body radiotherapy for pulmonary oligometastases, aiming to assess the clinical factors potentially affecting clinical outcomes. METHODS: The present series reports the outcomes of a cohort of 71 patients with pulmonary oligometastases with no extrapulmonary disease. All patients were treated with stereotactic body radiotherapy (SBRT) performed with volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) to up to five secondary lesions. Survival estimates were performed using the Kaplan-Meier method. RESULTS: A total of 98 lesions in 71 patients were treated from February 2014 to August 2020. The most frequent histologies were colorectal in 37.7%, lung cancer in 44.8%, head and neck cancer in 8.1%, and other in 9.4%. Median age was 71 years (range 32-93 years). Concurrent systemic therapy was administered in 32.3%. SBRT was delivered to a median total dose of 60 Gy (range 55-70 Gy) in 3-10 fractions for a median BED10 = 105 Gy (range 96-180 Gy). Median follow-up was 29.5 months (range 6-81), with no acute or late G > 2 adverse event. Our LC rates at 2 and 4 years were 92.4 and 89.8%, respectively. DPFS rates at 2 and 4 years were 45.3 and 27.2%, respectively. A second SBRT course was proposed in 21 patients (29.5%) who developed an oligoprogression, resulting in median time to second progression of 9 months (range 2-44) and 2­year PFS2 rate of 42.4%. At univariate analysis, patients with sequential oligometastases reported better OS rates (p = 0.002), which was also confirmed at multivariate analysis, where distant progression was also related to worse OS (p = 0.022). Higher local control rates relate to better PFS (p = 0.04). The 2­ and 4­year OS rates were 61 and 39.7% CONCLUSION: SBRT is feasible for pulmonary oligometastases with favorable outcomes and toxicity. At multivariate analysis, patients with sequential oligometastatic progression maintain a survival advantage. Also, local control was found to be related to improved PFS rates.

Cisplatin-induced nephrotoxicity in children: what is the best protective strategy?

INTRODUCTION: Platinum compounds, which are considerably effective for the treatment of childhood malignancies, have significantly contributed to the increase in long-term survival of children with cancer. Unfortunately, children receiving cisplatin-based chemotherapy have been known to be at risk for severe disabling adverse effects, such as nephrotoxicity. METHODS: A literature research of the MEDLINE PubMed database was conducted to identify articles published between 1980 and 2019 reviewing "Cisplatin AND mannitol." RESULTS: The primary pharmacodynamics and clinical characteristics of cisplatin were described, focusing on its renal toxic effects and potential preventive strategies, in order to improve clinical outcomes among children with cancer aged 1 to 14 years. Currently, selecting either hydration alone or hydration plus mannitol for preventing nephrotoxicity has been controversial considering the lack of guidelines to provide treatment recommendations both among adults and children. CONCLUSIONS: Appropriate knowledge regarding the pharmacokinetics and toxicological profile of cisplatin may help physicians prevent renal toxicity. Unfortunately, published data regarding the nephroprotective utility of adding mannitol appear to be inconclusive. As such, appropriate hydration remains the main fundamental strategy for reducing the risk of cisplatin-induced nephrotoxicity. Considering the increasing number of children safely cured of their tumours, it is imperative that those treated with cisplatin receive the most appropriate nephroprotective strategy for reducing the negative impact of platinum compounds on quality of life.

Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients.

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m2 are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody-antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.

Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment.

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Vincristine leads to VIPN through a complex mechanism of damage, which occurs not only on the microtubules, but also on the endothelium and the mitochondria of nerve cells. Furthermore, both patient-related risk factors (age, race, ethnicity and genetic polymorphisms) and treatment-related risk factors (dose, time of infusion and drug-drug interactions) are involved in the pathogenesis of VIPN. There is a lack of consensus about the prophylaxis and treatment of VIPN among pediatric oncologic patients, despite several molecules (such as gabapentin, pyridoxine and pyridostigmine, glutamic acid and glutamine) having been already investigated in clinical trials. This review describes the molecular mechanisms of VIPN and analyzes the risk factors and the principal drugs adopted for the prophylaxis and treatment of VIPN in pediatric patients with cancer.

A previously unrecognized Ankyrin-1 mutation associated with Hereditary Spherocytosis in an Italian family.

Hereditary spherocytosis is the most common inherited hemolytic anemia characterized by the presence of spherical-shaped erythrocytes on peripheral blood smear. The clinical manifestations of HS are highly variable, from severe forms to asymptomatic forms. HS is caused by defects in red blood cell membrane proteins, encoded by the ANK1, EPB42, SLC4A1, SPTA1 and SPTB genes. Mutation of the ANK 1 gene is the most common and inheritance is autosomal dominant in 75% of cases. In our case, heterozygous an ANK1 c.4123C > T mutation was identified in a 4-year-old girl, using targeted next-generation sequencing and Sanger sequencing.

Undifferentiated Embryonal Sarcoma of the Liver (UESL) in Adolescents: An Unexpected Diagnosis.

Definitive diagnosis of pediatric liver masses can be challenging, because clinical manifestations are nonspecific, and ultimate diagnosis may be delayed. We describe 2 patients with liver masses that initially were misdiagnosed and treated as infectious hepatic lesions. Only after histologic examination the correct diagnosis of undifferentiated embryonal sarcoma of the liver was defined. Both patients underwent a complete tumor resection followed by chemotherapy with a favorable outcome.

Intranasal therapy with opioids for children and adolescents with cancer: results from clinical studies.

Opioids are essential for the treatment of pain, which is a serious symptom for children and adolescents affected by cancer. Intranasal opioids may be very useful for the treatment of breakthrough pain in children and adolescents with cancer, for their little invasiveness, ease of administration, rapid onset of action, and high bioavailability. Intranasal drug delivery may be influenced by anatomical and physiological factors (nasal mucosa absorption area, mucociliary clearance, enzymatic activity, anatomical anomalies, chronic or inflammatory alterations of nasal mucosa), drug-related factors (molecular weight, solubility), and delivery device. Fentanyl is a lipophilic opioid commonly proposed for intranasal use among pediatric patients, but no studies have been conducted yet about intranasal use of other available opioids for management of pediatric cancer pain. In this review, we analyze several elements which may influence absorption of intranasal opioids in children and adolescents, with a focus on pharmacokinetics and therapeutic aspects of each opioid currently available for intranasal use.

Diagnostic Accuracy of 18F-FDG PET/CT in the Staging and Assessment of Response to Chemotherapy in Children With Ewing Sarcoma.

INTRODUCTION: The purpose of this study was to evaluate the potential role of fluorine-18 fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET-CT) in the staging and assessment of chemotherapy response in Ewing sarcoma. MATERIALS AND METHODS: For 13 patients with Ewing sarcoma, whole-body FDG PET-CT was assessed for site of primary disease, disease extent, and response to therapy. Chest CT, localized magnetic resonance imaging or CT of primary site, and bone scintigrams were evaluated for imaging features of the primary lesion and presence or absence of metastatic disease. Response to therapy was also assessed. Descriptive statistics are reported. RESULTS: Nine patients (69%) presented metastatic disease. All metastatic lung lesions were detected by spiral CT, but some failed to be detected using FDG PET-CT. As regards bone lesions, both FDG PET-CT and bone scans were able to identify bone metastasis, but FDG PET-CT identified more lesions than bone scans. All PET-CT scans at the end of the neoadjuvant chemotherapy showed a decreased FDG uptake. CONCLUSIONS: FDG PET-CT seems to be superior to bone scan in the detection of bone metastasis in all districts except skull bones. For pulmonary metastasis smaller than 7 mm, FDG PET-CT is less sensitive than CT. FDG PET-CT may have an important role in initial staging of Ewing sarcoma and subsequent evaluation of response to therapy.

Correction to: Multimodal treatment of pediatric patients with Askin's tumors: our experience.

[This corrects the article DOI: 10.1186/S12957-018-1434-2.].

Multimodal treatment of pediatric patients with Askin's tumors: our experience.

BACKGROUND: We report our experience and outcomes about the management of Askin's tumors [AT], which are rare primitive neuroectodermal tumors (PNETs) that develop within the soft tissue of the thoracopulmonary region, typically in children and adolescents. METHODS: We retrospectively analyzed the charts of 9 patients affected by AT (aged 6-15 years), treated at the Paediatric Oncology Unit of Gemelli University Hospital in Rome between January 2001 and December 2016. RESULTS: All nine patients underwent to biopsy followed by neoadjuvant chemotherapy. At the end of the neoadjuvant chemotherapy, they underwent to surgical removal of the residual tumor. Five patients with positive tumor margins and/or necrosis< 90% received local radiotherapy. Two patients with metastasis received an intensified treatment, with the addition of high dose adjuvant chemotherapy followed by peripheral blood stem cells rescue. No statistically significant correlation was found between outcome and gender; the presence of any metastasis and the radiotherapy. The overall survival was 65.14 months (95% confidence interval [95%CI], 45.81-84.48), and the 5 years survival was 60%, at a median follow-up of 53.1 months. CONCLUSION: Our study confirms that a multimodal treatment with surgery, chemotherapy, and radiotherapy may increase the survival in AT pediatric patients.

Renal toxicity and chemotherapy in children with cancer.

The clinical use of antineoplastic drugs can be limited by different drug-induced toxicities. Of these, renal dysfunction may be one of the most troublesome in that it can be cumulative and in general is only partially reversible with the discontinuation of the treatment. Renal toxicity may be manifested as a reduction of the glomerular filtration rate, electrolyte imbalances, or acute renal failure. Careful assessment of renal function has to be performed taking into account that the impairment of renal function is initially silent and only later may be clinically dramatic. When clinically indicated, the reduction or, in cases of severe nephrotoxicity, the suspension of chemotherapy should be considered to avoid the progressive deterioration of the compromised glomerular and/or tubular function.

Preliminary experience with video-assisted thoracic surgery lobectomy for lung malignancies: general considerations moving toward standard practice.

As part of the Second Catania Symposium on Thoracic Oncology, as we started the experience with video-assisted thoracic surgery (VATS) lobectomy for lung malignancies, we reviewed our data and argued some comments in a more general discussion. Operated patients with non-small-cell lung cancer were divided in two groups and compared: VATS (collected in a prospective database) and open (historical group). Out of 74 patients, 31 in group A and 44 in group B. The majority of patients in group A were stage I-II. Mean operative time was shorter in group A. Postoperative hospital stay was shorter in group A. There was no mortality. VATS is effective and safe to perform pulmonary lobectomy in our unit, and it represents our preferred approach for early-stage lung cancer.

Safe lumbar puncture under analgo-sedation in children with acute lymphoblastic leukemia.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) undergo multiple lumbar punctures (LPs) during their course of treatment for diagnostic and therapeutic purposes. LP is a stressful and painful procedure, affecting the quality of life of these children. Procedural analgo-sedation might improve the child's comfort and prevent the child's movements, reducing the risk of traumatic lumbar puncture with blasts (TLP+), mainly at diagnosis, when higher numbers of blast cells are circulating in the peripheral blood. The aim of this study was to evaluate the safety and efficacy of procedural analgo-sedation in children with ALL. METHODS: From September 2006 to November 2008, we performed a total of 252 lumbar punctures under deep sedation with propofol and ketamine in 25 children with ALL treated at our division. During the procedures, vital parameters were monitored and side effects were recorded. The efficacy of deep sedation was evaluated using Ramsay and Children's Hospital Eastern Ontario Pain scales. Cerebrospinal fluid was collected for chemical and cytological examinations. RESULTS: In all patients a satisfactory sedation and analgesia were achieved. The evaluation of vital parameters did not show any significant variation compared to baseline values. No side effects were recorded. Only 3 (1.2 %) of 252 lumbar punctures resulted in traumatic effects. CONCLUSION: To strongly improve comfort and quality of life of children with ALL and reduce the risk of TLP+ mainly at diagnosis, we recommend performing the lumbar punctures under analgo-sedation because it is a safe and effective procedure.

Anthropometric parameters as a tool for the prediction of metabolic and cardiovascular risk in childhood brain tumor survivors.

PURPOSE: To assess the prevalence of alterations in anthropometric parameters predictive of metabolic syndrome and cardiovascular risk among childhood brain tumor survivors. METHODS: Anthropometric parameters predictive of metabolic syndrome and cardiovascular risk were analyzed [height, weight, BMI, waist circumference, hip circumference, waist-height ratio (WHtR), waist-hip ratio (WHR, blood pressure] of 25 patients who survived childhood brain tumors. RESULTS: 21 patients (84%) showed alteration of at least one predictive anthropometric parameter. 11 patients (44%) showed a BMI > 75th percentile and 19 patients (76%) showed a pathological WHR value. A pathological WHtR (> 0.5), was identified in 17 patients (68%); the average WHtR observed was 0.53. 9 patients (36%) showed an alteration of all three anthropometric parameters considered. Comparing this subpopulation with the subpopulation with less than three altered parameters, a greater prevalence of the combined alteration was observed in the female sex compared to the male sex (67% vs. 26%). No significant differences were observed regarding the age of diagnosis and end of treatment nor the treatments carried out (chemotherapy, radiotherapy, steroid therapy) between the two groups. CONCLUSION: These results suggest that this population is at high risk of presenting pathological values of BMI, WHR and WHtR with consequent high risk of developing metabolic syndrome and cardiovascular diseases.

Evaluation of Metabolic and Cardiovascular Risk Measured by Laboratory Biomarkers and Cardiopulmonary Exercise Test in Children and Adolescents Recovered from Brain Tumors: The CARMEP Study.

In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-α, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk.