Systemic Therapies
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2021 ◽  
Author(s):  
Janie Y. Zhang ◽  
Pamela L. Kunz

Neuroendocrine tumors (NETs) are a heterogeneous clinical entity with a broad range of grade, pace of disease, functional status, and primary sites. Pathologic classification, diagnostic modalities, and therapeutic options for NETs have evolved considerably in the past decade. In part driven by these advances, incidence and prevalence of NETs are rising in the United States and the practicing oncologist is likely to encounter these in the clinic. However, there are no clear lines of therapy for unresectable or metastatic NETs, and sequencing of systemic therapies depends on consideration of patient and tumor characteristics including extent of disease, grade, pace of growth, functional status, primary site, somatostatin receptor status, performance status, and comorbidities. Familiarity with ongoing clinical trials will guide therapeutic decision making as well. In this review, we seek to provide a framework to formulate and tailor an individualized treatment plan for each patient with a NET.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shanshan Deng ◽  
Antonio Solinas ◽  
Diego F. Calvisi

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Patients with early-stage HCC can be treated successfully with surgical resection or liver transplantation. However, the usual late diagnosis of HCC precludes curative treatments, and systemic therapies are the only viable option for inoperable patients. Sorafenib, an orally available multikinase inhibitor, is a systemic therapy approved for treating patients with advanced HCC yet providing limited benefits. Consequently, new drugs have been developed to overcome sorafenib resistance and improve patients’ prognoses. A new promising strategy is using c-MET inhibitors, such as cabozantinib, as activation of c-MET occurs in up to 40% of HCC patients. In particular, cabozantinib, in combination with the checkpoint inhibitor atezolizumab, is currently in phase 3 clinical trial for HCC, and the results are eagerly awaited. Herein, we summarize and review the drugs approved for the treatment of advanced HCC, mainly focusing on the clinical and preclinical efficacy evaluation of cabozantinib. Also, we report the available preclinical data on cabozantinib-based combination therapies for HCC, current obstacles for cabozantinib therapy, and the future directions for cabozantinib-based treatment for HCC.


Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5127
Author(s):  
Yijun Wang ◽  
Tongyue Zhang ◽  
Mengyu Sun ◽  
Xiaoyu Ji ◽  
Meng Xie ◽  
...  

One of the major challenges in hepatocellular carcinoma (HCC) treatment is drug resistance and low responsiveness to systemic therapies, partly due to insufficient T cell infiltration. Myeloid-derived suppressor cells (MDSCs) are immature marrow-derived cell populations with heterogeneity and immunosuppression characteristics and are essential components of the suppressive tumor immune microenvironment (TIME). Increasing evidence has demonstrated that MDSCs are indispensable contributing factors to HCC development in a T cell-dependent or non-dependent manner. Clinically, the frequency of MDSCs is firmly linked to HCC clinical outcomes and the effectiveness of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Furthermore, MDSCs can also be used as prognostic and predictive biomarkers for patients with HCC. Therefore, treatments reprograming MDSCs may offer potential therapeutic opportunities in HCC. Here, we recapitulated the dynamic relevance of MDSCs in the initiation and development of HCC and paid special attention to the effect of MDSCs on T cells infiltration in HCC. Finally, we pointed out the potential therapeutic effect of targeting MDSCs alone or in combination, hoping to provide new insights into HCC treatment.


Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5077
Author(s):  
Jesper van Breeschoten ◽  
Alfonsus J.M. van den Eertwegh ◽  
Liesbeth C. de Wreede ◽  
Doranne L. Hilarius ◽  
Erik W. van Zwet ◽  
...  

Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hospital variation in treatment patterns and outcomes is evaluated in the Dutch Melanoma Treatment Registry. The aim of this study was to assess center variation in treatments and 2-year survival probabilities of patients diagnosed between 2013 and 2017 in the Netherlands. Methods: We selected patients diagnosed between 2013 and 2017 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. Centers’ performance on 2-year survival was evaluated using Empirical Bayes estimates calculated in a random effects model. Treatment patterns of the centers with the lowest and highest estimates for 2-year survival were compared. Results: For patients diagnosed between 2014 and 2015, significant center variation in 2-year survival probabilities was observed even after correcting for case-mix and treatment with new systemic therapies. The different use of new systemic therapies partially explained the observed variation. From 2016 onwards, no significant difference in 2-year survival was observed between centers. Conclusion: Our data suggest that between 2014 and 2015, after correcting for patient case-mix, significant variation in 2-year survival probabilities between Dutch melanoma centers existed. The use of new systemic therapies could partially explain this variation. In 2013 and between 2016 and 2017, no significant variation between centers existed.


2021 ◽  
Vol 2 (5) ◽  
Author(s):  
Maria Giuseppina Prete ◽  
Antonella Cammarota ◽  
Antonio D'Alessio ◽  
Valentina Zanuso ◽  
Lorenza Rimassa

Biliary tract cancers (BTCs) are aggressive tumors arising from different portions of the biliary tree and classified according to the anatomical location in intrahepatic (i) cholangiocarcinoma (CCA, iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). Due to their silent behavior, BTCs are frequently diagnosed at advanced stages when the prognosis is poor. The available chemotherapeutic options are palliative and unfortunately, most patients will die from their disease between 6 and 18 months from diagnosis. However, over the last decade, amounting interest has been posed on the genomic landscape of BTCs and deep-sequencing studies have identified different potentially actionable driver mutations. Hence, the promising results of the early phase clinical studies with targeted agents against isocitrate dehydrogenase (IDH) 1 mutation or fibroblast growth factor (FGF) receptor(FGFR) 2 aberrations inintrahepatic tumors, and other agents against humanepidermal growth factor receptor (HER) 2 overexpression/mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions or B-type Raf kinase (BRAF) mutations across different subtypes of BTCs, have paved the way for a “precision medicine” strategy for BTCs. Moreover, despite the modest results when used as monotherapy, beyond microsatellite instability-high (MSI-H) tumors, immune checkpoint inhibitors are being evaluated in combination with platinum-based chemotherapy, possibly further expanding the therapeutic landscape of advanced BTCs. This review aims to provide an overview of the approved systemic therapies, the promising results, and the ongoing studies to explore the current and future directions of advanced BTC systemic treatment.


2021 ◽  
Vol 8 ◽  
Author(s):  
Julio Ramírez ◽  
Ana Belén Azuaga-Piñango ◽  
Raquel Celis ◽  
Juan D. Cañete

PsA is characterized by a high prevalence of cardiovascular (CV) comorbidities. Recognizing these comorbidities is critical due to their influence on the quality of life and the choice of therapy. Imaging techniques also play an important role in the evaluation of the CV risk in psoriatic disease, improving the prediction of CV events when combined with clinical scores as a predictive tool. Meta-analyses point to a significant reduction in the incidence of CV events associated with the suppression of inflammatory activity when using systemic therapies. Consequently, the mortality rate in PsA patients has fallen in the last 40 years and is now similar to that of the general population, including cardiovascular causes. Obesity is an especially relevant CV comorbidity in patients with psoriatic disease, most of whom are overweight/obese. Body mass index (BMI) is a risk factor for PsA and a causal relationship with psoriasis has been demonstrated by Mendelian randomized studies. The study of fat distribution shows that patients with psoriasis are characterized by visceral fat accumulation, which correlates with CV risk measurements. These findings suggest that approaches to the prevention and treatment of psoriatic disease might come from targeting adiposity levels, in addition to the immune pathways. Weight loss treatment with low energy diets in patients with PsA has been associated with significant improvements in disease activity. Novel strategies using a multimorbidity approach, focused more on patients outcomes, are necessary to better address comorbidities, improve clinical outcomes and the quality of life of patients with psoriatic disease.


2021 ◽  
Vol 38 (04) ◽  
pp. 482-487
Author(s):  
Stephen J. Williams ◽  
William S. Rilling ◽  
Sarah B. White

Abstract Objective Transarterial radioembolization (TARE) offers a minimally invasive and safe treatment option for primary and metastatic hepatic malignancies. The benefits of TARE are manifold including prolonged overall survival, low associated morbidities, and improved time to progression allowing prolonged treatment-free intervals. The rapid development of new systemic therapies including immunotherapy has radically changed the treatment landscape for primary and metastatic liver cancer. Given the current climate, it is critical for interventional oncologists to understand the benefits of TARE relative to these other therapies. Therefore, this report aims to review quality-of-life outcomes and the cost comparisons of TARE as compared with systemic therapies.


2021 ◽  
Vol 156 ◽  
pp. S20
Author(s):  
Belinda A Campbell ◽  
Gabor Dobos ◽  
Zahra Haider ◽  
Martine Bagot ◽  
H. Miles Prince ◽  
...  

2021 ◽  
Vol 38 (04) ◽  
pp. 472-478
Author(s):  
Tarub S. Mabud ◽  
Ryan Hickey

Abstract 90Yttrium (Y90) radioembolization has been shown to improve outcomes for primary and metastatic liver cancers, but there is limited understanding of the optimal timing and safety of combining systemic therapies with Y90 treatment. Both therapeutic effects and toxicities could be synergistic depending on the timing and dosing of different coadministration paradigms. In particular, patients with liver-only or liver-dominant metastatic disease progression are often on systemic therapy when referred to interventional radiology for consideration of Y90 treatment. Interventional radiologists are frequently asked to offer insight into whether or not to hold systemic therapy, and for how long, prior to and following transarterial therapy. This study reviews the current evidence regarding the timing and safety of systemic therapy with Y90 treatment for hepatocellular carcinoma, metastatic colorectal carcinoma, intrahepatic cholangiocarcinoma, metastatic neuroendocrine tumors, and other hepatic metastases. A particular focus is placed on the timing, dosing, and toxicities of combined therapy.


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