Frontiers in oncology
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Frontiers in oncology · Jan 2020
ReviewRare Primary Central Nervous System Tumors in Adults: An Overview.
Overall, tumors of primary central nervous system (CNS) are quite common in adults with an incidence rate close to 30 new cases/100,000 inhabitants per year. Significant clinical and biological advances have been accomplished in the most common adult primary CNS tumors (i.e., diffuse gliomas). However, most CNS tumor subtypes are rare with an incidence rate below the threshold defining rare disease of 6.0 new cases/100,000 inhabitants per year. ⋯ The ERN for rare solid adult tumors is termed EURACAN. Within EURACAN, Domain 10 brings together the European patient advocacy groups (ePAGs) and physicians dedicated to improving outcomes in rare primary CNS tumors and also aims at supporting research, care and teaching in the field. In this review, we discuss the relevant biological and clinical characteristics, clinical management of patients, and research directions for the following types of rare primary CNS tumors: medulloblastoma, pineal region tumors, glioneuronal and rare glial tumors, ependymal tumors, grade III meningioma and mesenchymal tumors, primary central nervous system lymphoma, germ cell tumors, spinal cord tumors and rare pituitary tumors.
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Frontiers in oncology · Jan 2020
ReviewPrecision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer.
Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to tumors, it is proving more difficult to personalize radiotherapy regimens based on cancer biology. ⋯ Tumor molecular profiling has been used to develop radiosensitivity gene signatures, while the assessment of specific intracellular or secreted proteins, including circulating tumor cells, exosomes and DNA, has been performed to identify prognostic or predictive biomarkers of radiation response. Finally, the investigation of biomarkers related to radiation-induced toxicity could provide another means by which radiotherapy could become personalized. In this review, we discuss studies that have used these methods to identify or develop prognostic/predictive signatures of radiosensitivity, and how such assays could be used in the future as a means of providing personalized radiotherapy.
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Frontiers in oncology · Jan 2020
ReviewDual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment.
In the era of highly promising novel targeted-immunotherapy strategies for multiple myeloma (MM), the first series of clinical trials with CAR T-cells targeting the plasma cell-specific B-cell maturation antigen (BCMA) have shown excellent response rates. In the long-term, however, MM appears to escape the therapy likely due to initial low and heterogeneous expression or downregulation of BCMA expression. ⋯ CAR T-cell therapy for MM therefore faces two urgent challenges: (i) improving the efficacy of BCMA CAR T-cells and (ii) establishing a MM-selectivity even when CAR T-cells are directed against not entirely MM-specific target antigens. In this review, we will outline the current attempts to tackle these challenges, with a specific focus on how dual CAR targeting might be applied to tackle both issues.
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Frontiers in oncology · Jan 2020
ReviewPerspectives on the Treatment of Advanced Thyroid Cancer: Approved Therapies, Resistance Mechanisms, and Future Directions.
For differentiated thyroid cancer (DTC), systemic therapy with radioactive iodine (RAI) is utilized for radiosensitive disease, while for radioiodine refractory (RAIR) disease, current standard of care is treatment with multikinase tyrosine kinase inhibitors (TKI). For BRAF-mutant DTC or anaplastic thyroid cancer (ATC), treatment with inhibitors targeting BRAF and MEK are important advances. ⋯ Nevertheless, treatment of thyroid cancer resistant to current systemic therapies remains an important area of need. Resistance mechanisms are being elucidated, and novel therapies including combinations of BRAF and MEK inhibitors with RAI or other targeted therapies or TKIs combined with checkpoint inhibition are current areas of exploration.
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Frontiers in oncology · Jan 2020
Conventional Two-Stage Hepatectomy or Associating Liver Partitioning and Portal Vein Ligation for Staged Hepatectomy for Colorectal Liver Metastases? A Systematic Review and Meta-Analysis.
Background: Pushing the surgical limits for initially unresectable colorectal liver metastases (CRLM) are two approaches for sequential liver resection: two-stage hepatectomy (TSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS). However, the role of each treatment modality remains ill-defined. The present meta-analysis was designed to compare the safety, efficacy, and oncological benefits between ALPPS and TSH in the management of advanced CRLM. ⋯ The two treatments were similar in 90-day mortality (7 vs. 5%, p = 0.43), major complications (29 vs. 22%, p = 0.08), posthepatectomy liver failure (PHLF; 9 vs. 9%, p = 0.3), biliary leakage (11 vs. 14%, p = 0.86), length of hospital stay (27.95 vs. 26.88 days, p = 0.8), 1-year overall survival (79 vs. 84%, p = 0.61), 1-year recurrence (49 vs. 39%, p = 0.32), and 1-year disease-free survival (34 vs. 39%, p = 0.66). Cumulative meta-analyses indicated chronological stability for the pooled effect sizes of resection rate, 90-day mortality, major complications, and PHLF. Conclusions: Compared with TSH, ALPPS for advanced CRLM resulted in superior surgical efficacy with comparable perioperative mortality rate and short-term oncological outcomes, while this was at the cost of increased perioperative minor complications.