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Cancer Medicine Feb 2021Olaratumab is a monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFRα) and blocks receptor activation. We conducted a...
Olaratumab is a monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFRα) and blocks receptor activation. We conducted a phase 1 trial to evaluate the safety of olaratumab and determine a recommended dose in combination with three different chemotherapy regimens in children. Patients <18 years with relapsed/refractory solid or central nervous system tumors were enrolled to two dose levels of olaratumab. Patients received olaratumab monotherapy at 15 mg/kg (Part A) or 20 mg/kg (Part B) on Days 1 and 8 of the first 21-day cycle, followed by olaratumab combined with standard fixed doses of chemotherapy with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide by investigator choice for subsequent 21-day cycles. In Part C, patients received olaratumab 20 mg/kg plus assigned chemotherapy for all cycles. Parts A-C enrolled 68 patients across three chemotherapy treatment arms; olaratumab in combination with doxorubicin (N = 16), vincristine/irinotecan (N = 26), or ifosfamide (N = 26). Three dose-limiting toxicities (DLTs) occurred during olaratumab monotherapy (at 15 mg/kg, grade [G] 4 alanine aminotransferase [ALT]; at 20 mg/kg, G3 lung infection and G3 gamma-glutamyl transferase). One DLT occurred during vincristine/irinotecan with olaratumab 20 mg/kg therapy (G3 ALT). Treatment-emergent adverse events ≥G3 in >25% of patients included neutropenia, anemia, leukopenia, lymphopenia, and thrombocytopenia. Pharmacokinetic profiles of olaratumab with chemotherapy were within the projected range based on adult data. There was one complete response (rhabdomyosarcoma [Part B vincristine/irinotecan arm]) and three partial responses (two rhabdomyosarcoma [Part A doxorubicin arm and Part C doxorubicin arm]; one pineoblastoma [Part B vincristine/irinotecan arm]). Olaratumab was tolerable and safely administered in combination with chemotherapy regimens commonly used in children and adolescents.
Topics: Adolescent; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Child, Preschool; Doxorubicin; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Ifosfamide; Irinotecan; Male; Maximum Tolerated Dose; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Salvage Therapy; Tissue Distribution; Vincristine
PubMed: 33474828
DOI: 10.1002/cam4.3658 -
British Journal of Cancer Mar 2021Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs)...
BACKGROUND
Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs.
METHODS
Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914-2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population. We estimated cumulative incidence accounting for competing risk of death.
RESULTS
Hereditary survivors had statistically significantly increased SMN risk (N = 239; SIR = 11.9; 95% confidence interval [CI] 10.4-13.5), with SIRs >80-fold for sarcomas, nasal cavity tumours and pineoblastoma. Significantly increased risks were also observed for melanoma and central nervous system, oral cavity and breast SMNs (SIRs = 3.1-17), but not the uterus, kidney, lung, bladder, pancreas or other types. Cumulative incidence 50 years following hereditary retinoblastoma was 33.1% (95% CI 29.0-37.2) for a first SMN and 6.0% (95% CI 3.8-8.2) for a second SMN. SMN risk was not increased after nonhereditary retinoblastoma (N = 25; SIR = 0.8; 95% CI 0.5-1.2).
CONCLUSION
Beyond the established sarcoma and melanoma risks after hereditary retinoblastoma, we demonstrate increased risk for a more limited number of epithelial malignancies than previously suggested. Cumulative incidence estimates emphasise long-term SMN burden after hereditary retinoblastoma.
Topics: Adult; Cancer Survivors; Female; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Incidence; Male; Middle Aged; Neoplasms, Second Primary; Prognosis; Retinal Neoplasms; Retinoblastoma; Survival Rate; United States
PubMed: 33473166
DOI: 10.1038/s41416-020-01248-y -
Iranian Journal of Allergy, Asthma, and... Aug 2020Brain tumors are the rarest cause of cerebrospinal fluid rhinorrhea. Non-traumatic cerebrospinal fluid rhinorrhea is also a relatively rare condition. It may be...
Brain tumors are the rarest cause of cerebrospinal fluid rhinorrhea. Non-traumatic cerebrospinal fluid rhinorrhea is also a relatively rare condition. It may be misdiagnosed as allergic rhinitis or chronic sinusitis and lead to unsuitable treatment. We described a 34-year-old man who came to our allergy clinic with a chief complaint of clear rhinorrhea from his left nostril with more than four years of duration. Onlyhypertrophy of left inferior concha was found in the clinical examination. His rhinorrhea aggravated when bending forward. So we were suspicious of CSF rhinorrhea. MRI was done for him and demonstrated a large tumor in the pineal region. The patient underwent surgery with resection of the mass via an infratentorial-supracerebellar approach. This case showed the role of maintaining differential diagnosis for a common complaint; rhinitis which is seen as usual.
Topics: Adult; Carcinoma, Squamous Cell; Cerebrospinal Fluid Rhinorrhea; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Pinealoma; Rhinitis; Symptom Assessment
PubMed: 33463112
DOI: 10.18502/ijaai.v19i4.4121 -
Ophthalmology. Retina Aug 2021
Topics: Adult; Biopsy; Brain; Female; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Pregnancy; Pregnancy Complications, Neoplastic; Retina; Retinal Neoplasms; Retinoblastoma; Ultrasonography
PubMed: 33373716
DOI: 10.1016/j.oret.2020.12.017 -
Clinical Neuroradiology Dec 2020
Topics: Adolescent; Brain Neoplasms; Glioma; Headache; Humans; Magnetic Resonance Imaging; Male; Neuropathology; Vision Disorders
PubMed: 33230629
DOI: 10.1007/s00062-020-00973-4 -
Frontiers in Endocrinology 2020Pineal metastasis is an exceedingly rare finding in patients with systemic malignancies. Such lesions are typically the manifestation of a primary lung cancer;...
Pineal metastasis is an exceedingly rare finding in patients with systemic malignancies. Such lesions are typically the manifestation of a primary lung cancer; nonetheless, a variety of malignancies have been reported to disseminate to the pineal gland including gastrointestinal, endocrine, and skin cancers, among others. However, to our knowledge, pineal gland metastasis without a primary origin has yet to be described. Carcinoma of unknown primary origin is a heterogeneous group of cancers characterized by the presence of metastatic disease without an identifiable primary tumor on metastatic workup. Here, we present a case of a 65-year-old male found to have a heterogeneously enhancing lesion of the pineal gland as well as an enhancing lesion of the left cerebellar hemisphere. Comprehensive metastatic workup demonstrated multifocal metastatic adenopathy without an identifiable primary lesion. Stereotactic biopsy of the pineal lesion revealed poorly differentiated carcinoma with an immunophenotype most consistent with gastrointestinal origin. To our knowledge, this is the first case to describe a pineal gland metastasis without a primary origin. We discuss the relevant literature on pineal gland metastases as well as carcinoma of unknown primary origin.
Topics: Aged; Cell Differentiation; Humans; Male; Neoplasms, Unknown Primary; Pinealoma; Prognosis
PubMed: 33193110
DOI: 10.3389/fendo.2020.597773 -
Frontiers in Oncology 2020[This corrects the article DOI: 10.3389/fonc.2020.01021.].
[This corrects the article DOI: 10.3389/fonc.2020.01021.].
PubMed: 33123489
DOI: 10.3389/fonc.2020.594049 -
Data in Brief Oct 2020Methylation profiling is widely used to study tumor biology and perform cluster analysis, particularly in brain cancer research where tissue biopsies are scarce. We have...
Methylation profiling is widely used to study tumor biology and perform cluster analysis, particularly in brain cancer research where tissue biopsies are scarce. We have recently reported on the development of novel mouse models for germ line mutations in pineoblastoma (, 2020). Here, we present unpublished methylation profiling of 8 Rb-deleted/p53-deleted pineoblastoma from our mouse model as well as 3 normal cerebellum tissues as control. The primary dataset can be accessed via SRA (PRJNA638504). These methylation data can be used to perform inter- and intra-species comparisons with other brain cancers as well as with specific subtypes of pineoblastoma, and to investigate potential epigenetic mechanisms and pathways underlying Rb-deficient pineoblastoma-genesis..
PubMed: 32923545
DOI: 10.1016/j.dib.2020.106229 -
Cancer Management and Research 2020Intracranial pineoblastomas are rare neoplasms with poor prognosis. The aim of this study was to describe the independent prognostic factors and treatment strategies for...
OBJECTIVE
Intracranial pineoblastomas are rare neoplasms with poor prognosis. The aim of this study was to describe the independent prognostic factors and treatment strategies for overall survival in pediatric and adult patients.
METHODS
Sixty-four patients were surgically treated between January 2012 and December 2018.
RESULTS
The series included 37 (57.8%) males and 27 (42.2%) females. Gross total resection was achieved in 41 (64.1%) cases, and the 1-, 3-, and 5-year rates of overall survival were 86.3, 52.3, and 36.6%, respectively. In the pediatric group (n=42), 28 patients (66.7%) were male, with the median, and the mean age was 4 and 6.2±4.7 years, respectively. After a median follow-up of 25.0 months, twenty-six patients (61.9%) died, and the 1-, 3-, and 5-year rates of overall survival were 84.9, 46.4, and 26.7%, respectively. Postoperative radiotherapy (p=0.058) and postoperative chemotherapy (p=0.183) had a positive influence on the increased overall survival. Meanwhile, postoperative radiotherapy combined with chemotherapy following surgery had a positive impact on overall survival (p=0.174, Log rank). In the adult group, the mean overall survival was 67.3±9.3 months (range, 0.8-95.3 months), and the 1-, 3-, and 5-year rates of overall survival were 89.5, 64.4, and 64.4%, respectively. In this group, no statistical association was observed between clinical factors and outcomes. However, patients who received postoperative radiotherapy (60.7 vs 57.6 month, mean survival; p=0.510, Log rank) or chemotherapy (63.0 vs 59.9 month, mean survival; p=0.404, Log rank) had better survival rates compared with those who declined.
CONCLUSION
In the pediatric group, surgery with postoperative radiotherapy and chemotherapy was a favorable factor for overall survival. In the adult group, a positive trend in overall survival was found when patients received radiation and/or chemotherapy following surgery.
PubMed: 32884348
DOI: 10.2147/CMAR.S258476 -
Frontiers in Oncology 2020Pineoblastoma (PB) is a rare neoplasm of the central nervous system. This analysis aimed to identify factors and establish a predictive model for the prognosis of adult...
Pineoblastoma (PB) is a rare neoplasm of the central nervous system. This analysis aimed to identify factors and establish a predictive model for the prognosis of adult patients with PB. Data for 213 adult patients with PB (Surveillance, Epidemiology, and End Results database) were randomly divided into primary and validation cohorts. A predictive model was established and optimized based on the Akaike Information Criterion and visualized by a nomogram. Its predictive performance (concordance index and receiver operating characteristic curve) and clinical utility (decision curve analyses) were evaluated. We internally and externally validated the model using calibration curves. Multivariate Cox regression analysis identified age, year of diagnosis, therapy, tumor size, and tumor extension as independent predictors of PB. The model exhibited great discriminative ability (concordance index of the nomogram: 0.802; 95% confidence interval: 0.78-0.83; area under the receiver operating characteristic curve: ranging from 0.7 to 0.8). Calibration plots (probability of survival) showed good consistency between the actual observation and the nomogram prediction in both cohorts, and the decision curve analyses demonstrated great clinical utility of the nomogram. The nomogram is a useful and practical tool for evaluating prognosis and determining appropriate therapy strategies.
PubMed: 32793463
DOI: 10.3389/fonc.2020.01021