Neutron radiation therapy for advanced thyroid cancers.
Ontology highlight
ABSTRACT:
SUBMITTER: Chapman TR
PROVIDER: S-EPMC5514010 | biostudies-other | 2016 Jul-Sep
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Background: Thyroid cancer is a common malignancy whose detection has increased significantly in past decades. Most of the increased incidence is due to detection of early well-differentiated thyroid cancer, but the incidence of more advanced thyroid cancers has increased as well. Recent methodological advancements have allowed for a deep understanding of the molecular underpinnings of the various types of thyroid cancer. Summary: Thyroid cancers harbor a high frequency of potential druggable molecular alterations, including the highest frequency of oncogenic driver kinase fusions seen across all solid tumors. Analyses of poorly differentiated and anaplastic thyroid carcinoma confirmed that these tumors develop from more well-differentiated follicular-derived thyroid cancers through acquired additional mutations. The recognition of driver genomic alterations in thyroid cancers not only predicts tumor phenotype but also now can inform treatment approaches. Conclusions: Major progress in understanding the oncogenic molecular underpinnings across the array of thyroid cancers has led to considerable gains in gene-specific systemic therapies for many cancers. This article focuses on the molecular characteristics of aggressive follicular-derived thyroid cancers and medullary thyroid cancer and highlights advancements in treating thyroid cancer in the era of targeted therapy.
| S-EPMC8591086 | biostudies-literature
Project description:Enormous amounts of childhood thyroid cancers, mostly childhood papillary thyroid carcinomas (PTCs), after the Chernobyl nuclear power plant accident have revealed a mutual relationship between the radiation exposure and thyroid cancer development. While the internal exposure to radioactive 131I is involved in the childhood thyroid cancers after the Chernobyl accident, people exposed to the external radiation, such as atomic-bomb (A-bomb) survivors, and the patients who received radiation therapy, have also been epidemiologically demonstrated to develop thyroid cancers. In order to elucidate the mechanisms of radiation-induced carcinogenesis, studies have aimed at defining the molecular changes associated with the thyroid cancer development. Here, we overview the literatures towards the identification of oncogenic alterations, particularly gene rearrangements, and discuss the existence of radiation signatures associated with radiation-induced thyroid cancers.
| S-EPMC6770066 | biostudies-literature
Project description:Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients' overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor's ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.
| S-EPMC5817719 | biostudies-literature
Project description:Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using non-invasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. In addition, functional imaging technologies, such as PET, can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Regardless, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.
| S-EPMC9221296 | biostudies-literature
Project description:Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance.Experimental Design: The genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed.Results: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated thyroid cancers and ATCs. Copy number losses and mutations of CDKN2A and CDKN2B, amplification of CCNE1, amplification of receptor tyrosine kinase genes KDR, KIT, and PDGFRA, amplification of immune evasion genes CD274, PDCD1LG2, and JAK2, and activating point mutations in small GTPase RAC1 were associated with ATC. An association of KDR, KIT, and PDGFRA amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown in vitro Three genetically distinct types of ATCs are proposed.Conclusions: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed. Clin Cancer Res; 24(13); 3059-68. ©2018 AACR.
| S-EPMC6030480 | biostudies-literature
Project description:BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. In the advanced setting, MCC is often treated with immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies. X-ray radiation therapy (XRT) is commonly used for palliation. There is an unmet need for new treatment options in patients progressing on immunotherapy and XRT. We present 2 patients with progressive MCC who were successfully treated with high linear energy transfer neutron radiation therapy (NRT).Clinical observationsPatient A, an 85-year-old white male with chronic lymphocytic leukemia had progressive MCC with multiple tumors on the face despite prior XRT and ongoing treatment with pembrolizumab. The 5 most symptomatic lesions were treated with a short course of NRT (2 × 3 Gy) while continuing pembrolizumab. All irradiated facial lesions demonstrated a complete response 2 weeks after NRT. Remarkably, an additional 4 lesions located outside the NRT fields also completely resolved. Patient B, a 78-year-old white male with no immunosuppressive condition had recurrent MCC in the scalp and bilateral cervical nodes. The painful, ulcerative tumors on his scalp were progressing despite multiple courses of XRT and multiple immunotherapy regimens, including pembrolizumab. He was treated with NRT (16-18 Gy) to the scalp and had a complete response with successful palliation. While his disease subsequently progressed outside the NRT fields, the response to NRT bridged him to receive further investigational immunotherapies, and he remains disease free 3 years later.ConclusionShort courses of high linear energy transfer particle therapy deserve consideration as a promising modality for local tumor control in XRT refractory tumors. The out-of-field response suggests that NRT has potential for synergizing with immunotherapy. While more data are required to identify optimal NRT parameters, the NRT dose that potentiates an antitumor immune response appears to be well below organ-at-risk tolerance.
| S-EPMC6871593 | biostudies-literature
Project description:Radiation therapy (RT) represents an integral part of a multimodality treatment plan in the definitive, preoperative and postoperative management of non-small cell lung cancer (NSCLC). Technological advances in RT have enabled a shift from two-dimensional radiotherapy to more conformal techniques. Three-dimensional conformal radiotherapy (3DCRT), the current minimum technological standard for treating NSCLC, allows for more accurate delineation of tumor burden by using computed tomography-based treatment planning instead of two-dimensional radiographs. Intensity-modulated RT (IMRT) and proton therapy represent advancements over 3DCRT that aim to improve the conformity of RT and provide the possibility for dose escalation to the tumor by minimizing radiation dose to organs at risk. Both techniques likely confer benefits to certain anatomic subgroups of NSCLC requiring RT. This article reviews pertinent studies evaluating the use of IMRT and proton therapy in locally advanced NSCLC, and outlines challenges, indications for use, and areas for future research.
| S-EPMC6123184 | biostudies-literature
Project description:After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers.
| S-EPMC4399027 | biostudies-literature
Project description:Esophageal carcinoma is one of the most aggressive malignant diseases. At present, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy are regarded as the standard modalities for the treatments of locally advanced esophageal cancers based on several landmark trials. However, the optimal regimen, radiation dose, and surgical intervals are uncertain and the rate of recurrence after neoadjuvant therapy is high. Patients receiving neoadjuvant therapy and reaching a pathological complete response have been reported to have a better survival benefit and a fewer recurrence risk than those non-pathological complete responses. Nevertheless, less than half of patients will reach a pathological complete response after neoadjuvant therapy, and the methods to evaluate the efficacy after neoadjuvant therapy accurately are limited. Immune checkpoint inhibitors have been recommended for the treatments of advanced esophageal cancers. Recently, research has been beginning to evaluate the safety and efficacy of immunotherapy combined with neoadjuvant therapy. Here, we will review and discuss the development of the neoadjuvant therapy of locally advanced esophageal cancers and unsolved clinical problems.
| S-EPMC9021527 | biostudies-literature
Project description:Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We examined tissues from 26 Ukrainian patients with thyroid cancer who were younger than 10 years of age and living in contaminated areas during the time of the Chernobyl nuclear reactor accident. We identified nonoverlapping somatic driver mutations in all 26 cases through candidate gene assays and next-generation RNA sequencing. We found that 22 tumors harbored fusion oncogenes that arose primarily through intrachromosomal rearrangements. Altogether, 23 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the 2 somatic rearrangements resulting in fusion of transcription factor ETS variant 6 (ETV6) with neurotrophic tyrosine kinase receptor, type 3 (NTRK3) and fusion of acylglycerol kinase (AGK) with BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. Fusion oncogenes were less prevalent in tumors from a cohort of children with pediatric thyroid cancers that had not been exposed to radiation but were from the same geographical regions. Radiation-induced thyroid cancers provide a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program.
| S-EPMC3809792 | biostudies-literature