1,721,157 research outputs found
Antibiotic Therapy: The Cornerstone of Iatrogenic Resistance to Immune Checkpoint Inhibitors
No full text
Measuring the Invisible: Circulating Tumor DNA as a Predictive and Prognostic Marker of Response to Adjuvant Chemotherapy in Resected Colorectal Cancer
No full textBack from the brink: EGFR inhibition in gastroesophageal cancer
No full textGastroesophageal adenocarcinomas (GEA) remain difficult to treat with limited targeted therapeutics. Negative results from randomized trials of Epidermal Growth Factor Receptor inhibitors (EGFRi) in molecularly unselected GEA patients have hampered the development of EGFRi in the gastroesophageal cancer space. A recent study reopens the game
NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy
No full text: The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)-a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk, and ultimately increase survival of patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC
Immunotherapy Benefit Over Best Supportive Care in Hepatocellular Cancer With Child-Pugh B Dysfunction-Reply
No full textBreaking the Child-Pugh Dogma in Hepatocellular Carcinoma
Full text linkThe albumin-bilirubin (ALBI) score may be a more objective and sensitive method of assessing liver function in patients with hepatocellular carcinoma than the Child-Pugh score, the current standard approach
ctDNA: A Gateway for Personalized Risk Stratification in Surgically Resectable Hepatocellular Cancer
No full text: While deemed potentially curative, surgical resection of hepatocellular carcinoma (HCC) is associated with >70% risk of post-operative relapse. Recurrence is uniquely multifactorial in HCC, potentially stemming from metachronous re-occurrence of the original tumor or de novo cancerization. Circulating tumor DNA may improve personalized risk stratification post-resection, a setting where adjuvant immunotherapy has failed to provide survival benefits
Merits and boundaries of the BCLC staging and treatment algorithm: Learning from the past to improve the future with a novel proposal
No full text: In this Expert Opinion, we thoroughly analyse the Barcelona Clinic Liver Cancer (BCLC) staging and treatment algorithm for hepatocellular carcinoma (HCC) that, since 1999, has standardised HCC management, offering a structured approach for the prognostic evaluation and treatment of patients with HCC. The first part of the article presents the strengths and evolutionary improvements of the BCLC staging system. Nevertheless, both patient characteristics and available treatments have changed in the last two decades, limiting the role of the BCLC criteria for treatment allocation in a growing number of patients. As therapeutic options expand and become more effective, the stage-linked treatment decision-making algorithm may lead to undertreatment and suboptimal outcomes for patients with disease beyond early-stage HCC. Consequently, strict adherence to BCLC criteria is limited in expert centres, particularly for patients diagnosed beyond early-stage HCC. Although the BCLC system remains the benchmark against which other therapeutic frameworks must be judged, the era of precision medicine calls for patient-tailored therapeutic decision-making (by a multidisciplinary tumour board) rather than stage-dictated treatment allocation. Acknowledging this conceptual difference in clinical management, the second part of the article describes a novel "multiparametric therapeutic hierarchy", which integrates a comprehensive assessment of clinical factors, biomarkers, technical feasibility, and resource availability. Lastly, considering the increasing efficacy of locoregional and systemic treatments, the concept of "converse therapeutic hierarchy" is introduced. These treatments can increase the feasibility (conversion approach) and effectiveness (adjuvant approach of systemic therapy) of potentially curative approaches to greatly improve clinical outcomes
Perspectives on the neoadjuvant use of immunotherapy in hepatocellular carcinoma
Full text linkImmune checkpoint inhibitor (ICI) therapy is an increasingly used treatment modality across the various stages of hepatocellular cancer (HCC). There is currently no standard peri-operative therapy for HCC, despite a high probability of recurrence. Emerging studies in a variety of tumors demonstrate significant pathologic and immune responses to neoadjuvant immunotherapy. Unlike kinase inhibitors and other targeted therapies, which demonstrated no benefit in the adjuvant setting and fail to induce significant responses, ICIs can induce radiologically appreciable reduction in disease burden, which make ICI combinations an appealing downstaging strategy in patients early or locally advanced disease. Additionally, induction of anti-tumor immunity in the pre-operative setting may induce protracted T-cell response that, in the post-operative phase, may be capable of eliminating micro-metastatic disease and prevent future recurrence. In this review, we discuss the rationale and clinical hurdles that underlie optimal integration of immunotherapy in the pre-operative setting, highlighting the positive impact on surgical and oncological outcomes in patients with early-stage HCC
- …
