Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial

Sherman, Eric J.; Harris, Jonathan; Bible, Keith C.; Xia, P.; Ghossein, Ronald; Chung, Christine H.; Riaz, Nadeem; Gunn, G.B.; Foote, Robert L.; Yom, Sue S.; Wong, Stuart J.; Koyfman, Shlomo A.; Dzeda, Michael; Clump, David A.; Shah, Manisha H.; Redmond, Kevin P.; Torres-Saavedra, Pedro A.; Le, Quynh‐Thu; Lee, Nancy Y.

doi:10.1016/s1470-2045(22)00763-x

Cited by 18 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, in a recent phase 2 trial, 71 patients with ATC (one-third of whom harboured distant metastases) were randomized to weekly paclitaxel, daily pazopanib and concurrent radiotherapy or paclitaxel and radiotherapy alone. Overall survival in the control arm was 7.3 months, and the response rate was 33.3% ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Combinatorial hypofractionated radiotherapy and pembrolizumab in anaplastic thyroid cancer

Tan,

Tay,

Ong

et al. 2024

European Thyroid Journal

View full text Add to dashboard Cite

Objectives Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT). Methods In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200mg every 3-4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent Lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment. Results At median follow-up of 32.6 months (IQR: 26.4-38.8), of a cohort of 5 patients, BOR was 80%; with 2 complete responses (CR) and 2 partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2-NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7-100) for both. Treatment was well-tolerated, with mostly grade 1-2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab. Conclusions Herein, we reported a case series of 5 patients with ATC, with 2 long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Combinatorial hypofractionated radiotherapy and pembrolizumab in anaplastic thyroid cancer

Tan,

Tay,

Ong

et al. 2024

European Thyroid Journal

View full text Add to dashboard Cite

show abstract

“…Due to the correlative nature of our study, in vitro analysis must be conducted to confirm the role of these microbes in PTC incidence and progression. Although CPTC, FVPTC, and TCPTC were the primary tumors available from TCGA, future studies should also characterize how these microbes may uniquely contribute to oncogenesis in other forms of thyroid cancer [ 62 , 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Dysregulation of the Mycobiome and Archaeome and Distinct Oncogenic Characteristics according to Subtype and Gender in Papillary Thyroid Carcinoma

John

Yalamarty

Barakchi

et al. 2023

IJMS

View full text Add to dashboard Cite

Papillary Thyroid Carcinoma (PTC) is characterized by unique tumor morphology, treatment response, and patient outcomes according to subtype and gender. While previous studies have implicated the intratumor bacterial microbiome in the incidence and progression of PTC, few studies have investigated the potential role of fungal and archaeal species in oncogenesis. In this study, we aimed to characterize the intratumor mycobiome and archaeometry in PTC with respect to its three primary subtypes: Classical (CPTC), Follicular Variant (FVPTC), and Tall Cell (TCPTC), and also with respect to gender. RNA-sequencing data were downloaded from The Cancer Genome Atlas (TCGA), including 453 primary tumor tissue samples and 54 adjacent solid tissue normal samples. The PathoScope 2.0 framework was used to extract fungal and archaeal microbial read counts from raw RNA-sequencing data. Overall, we found that the intratumor mycobiome and archaeometry share significant similarities in CPTC, FVPTC, and TCPTC, although most dysregulated species in CPTC are underabundant compared to normal. Furthermore, differences between the mycobiome and archaeometry were more significant between males and females, with a disproportionate number of fungal species overabundant in female tumor samples. Additionally, the expression of oncogenic PTC pathways was distinct across CPTC, FVPTC, and TCPTC, indicating that these microbes may uniquely contribute to PTC pathogenesis in each subtype. Furthermore, differences in the expression of these pathways were observed between males and females. Finally, we found a specific panel of fungi to be dysregulated in BRAF V600E-positive tumors. This study demonstrates the potential importance of microbial species to PTC incidence and oncogenesis.

show abstract

“…Chemotherapy added to radiation therapy further improves survival compared to radiation alone in resected cases as well as in unresected cases[ 73 ]. A randomized controlled phase II trial from 34 centers in the United States including 89 patients showed that the combination of paclitaxel chemotherapy with pazopanib, a multitargeted inhibitor of tyrosine kinase receptors and radiation therapy, was feasible, safe and promising[ 74 ].…”

Section: Managementmentioning

confidence: 99%

“…Radiotherapy can be applied as a neoadjuvant or definitive adjuvant modality generally by external beam radiation therapy (EBRT), which accelerates hyperfunction and improves median overall survival[ 24 , 48 , 77 ]. It is a necessary part of the current multimodality treatment combined with surgery, chemotherapy, targeted therapy and novel immunotherapy[ 9 , 42 , 63 , 73 , 74 ].…”

Section: Managementmentioning

confidence: 99%

Update on current diagnosis and management of anaplastic thyroid carcinoma

Pavlidis,

Galanis,

Pavlidis

2023

World J Clin Oncol

View full text Add to dashboard Cite

Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%. However, the undifferentiated or anaplastic type accounting for < 0.2%, usually in elderly individuals, exhibits a dismal prognosis with rapid growth and disappointing outcomes. It is the most aggressive form of thyroid carcinoma, with a median survival of 5 mo and poor quality of life (airway obstruction, dysphagia, hoarseness, persistent pain). Early diagnosis and staging are crucial. Diagnostic tools include biopsy (fine needle aspiration, core needle, open surgery), high-resolution ultrasound, computed tomography, magnetic resonance imaging, [(18)F]fluoro-D-glucose positron emission tomo-graphy/computed tomography, liquid biopsy and microRNAs. The BRAF gene (BRAF-V600E and BRAF wild type) is the most often found molecular factor. Others include the genes RET, KRAS, HRAS, and NRAS . Recent management policy is based on surgery, even debulking, chemotherapy (cisplatin or doxorubicin), radiotherapy (adjuvant or definitive), targeted biological agents and immunotherapy. The last two options constitute novel hopeful management modalities improving the overall survival in these otherwise condemned patients. Anti-programmed death-ligand 1 antibody immunotherapy, stem cell targeted therapies, nanotechnology achievements and artificial intelligence imple-mentation provide novel promising alternatives. Genetic mutations determine molecular pathways, thus indicating novel treatment strategies such as anti-BRAF, anti-vascular endothelial growth factor-A, and anti-epidermal growth factor receptor. Treatment with the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has been approved by the Food and Drug Administration in cases with BRAF-V600E gene mutations and is currently the standard care. This neoadjuvant treatment followed by surgery ensures a two-year overall survival of 80%. Prognostic factors for improved outcomes have been found to be younger age, earlier tumor stage and radiation therapy. A multidisciplinary approach is necessary, and the therapeutic plan should be individualized based on surveillance and epidemiology end results.

show abstract

Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial

Cited by 18 publications

References 22 publications

Combinatorial hypofractionated radiotherapy and pembrolizumab in anaplastic thyroid cancer

Combinatorial hypofractionated radiotherapy and pembrolizumab in anaplastic thyroid cancer

Transcriptomic Analysis Reveals Dysregulation of the Mycobiome and Archaeome and Distinct Oncogenic Characteristics according to Subtype and Gender in Papillary Thyroid Carcinoma

Update on current diagnosis and management of anaplastic thyroid carcinoma

Contact Info

Product

Resources

About