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World Journal of Gastrointestinal... Nov 2021Cancer of the biliary confluence also known as hilar cholangiocarcinoma (HC) or Klatskin tumor, is a rare type of neoplastic disease constituting approximately 40%-60%... (Review)
Review
Cancer of the biliary confluence also known as hilar cholangiocarcinoma (HC) or Klatskin tumor, is a rare type of neoplastic disease constituting approximately 40%-60% of intrahepatic malignancies, and 2% of all cancers. The prognosis is extremely poor and the majority of Klatskin tumors are deemed unresectable upon diagnosis. Most patients with unresectable bile duct cancer die within the first year after diagnosis, due to hepatic failure, and/or infectious complications secondary to biliary obstruction. Curative treatments include surgical resection and liver transplantation in highly selected patients. Nevertheless, very few patients are eligible for surgery or transplant at the time of diagnosis. For patients with unresectable HC, radiotherapy, chemotherapy, photodynamic therapy, and liver-directed minimally invasive procedures such as percutaneous image-guided ablation and intra-arterial chemoembolization are recommended treatment options. This review focuses on currently available treatment options for unresectable HC and discusses future perspectives that could optimize outcomes.
PubMed: 34853644
DOI: 10.4251/wjgo.v13.i11.1696 -
Frontiers in Immunology 2022The existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC.
METHODS
The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer's perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA.
RESULTS
We identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable.
CONCLUSION
Sintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.
Topics: Humans; Carcinoma, Hepatocellular; Sorafenib; Cost-Effectiveness Analysis; Bevacizumab; Network Meta-Analysis; Biosimilar Pharmaceuticals; Liver Neoplasms; Immunotherapy
PubMed: 36713376
DOI: 10.3389/fimmu.2022.1103055 -
Future Oncology (London, England) May 2022Xevinapant is a first-in-class antagonist of inhibitor of apoptosis proteins, which enhances cancer cell sensitivity to chemotherapy and radiotherapy. In a phase...
Xevinapant is a first-in-class antagonist of inhibitor of apoptosis proteins, which enhances cancer cell sensitivity to chemotherapy and radiotherapy. In a phase II randomized study in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), xevinapant plus standard-of-care cisplatin-based chemoradiotherapy (CRT) showed superior efficacy versus placebo plus CRT. Here, we describe the design of TrilynX (NCT04459715), a randomized, double-blind, phase III study. In total, 700 patients with unresected LA SCCHN will be randomized 1:1 to receive xevinapant or placebo plus standard-of-care CRT followed by xevinapant monotherapy or placebo. The primary end point is event-free survival by blinded independent review committee. Secondary end points include progression-free survival, locoregional control, overall survival and safety.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Head and Neck Neoplasms; Humans; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck
PubMed: 35172587
DOI: 10.2217/fon-2021-1634 -
Cancers Mar 2020Unresectable hepatocellular carcinoma (HCC) was first removed successfully with total hepatectomy and liver transplantation (LT) in a child over five decades ago. Since... (Review)
Review
Unresectable hepatocellular carcinoma (HCC) was first removed successfully with total hepatectomy and liver transplantation (LT) in a child over five decades ago. Since then, children with unresectable liver cancer have benefitted greatly from LT and a confluence of several equally important endeavors. Regional and trans-continental collaborations have accelerated the development and standardization of chemotherapy regimens, which provide disease control to enable LT, and also serve as a test of unresectability. In the process, tumor histology, imaging protocols, and tumor staging have also matured to better assess response and LT candidacy. Significant trends include a steady increase in the incidence of and use of LT for hepatoblastoma, and a significant improvement in survival after LT for HCC with each decade. Although LT is curative for most unresectable primary liver sarcomas, such as embryonal sarcoma, the malignant rhabdoid tumor appears relapse-prone despite chemotherapy and LT. Pediatric liver tumors remain rare, and diagnostic uncertainty in some settings can potentially delay treatment or lead to the selection of less effective chemotherapy. We review the current knowledge relevant to diagnosis, LT candidacy, and post-transplant outcomes for these tumors, emphasizing recent observations made from large registries or larger series.
PubMed: 32204368
DOI: 10.3390/cancers12030720 -
Hepatic Medicine : Evidence and Research 2017Although rare, hepatoblastoma is the most common pediatric liver tumor. Complete resection is a critical component for cure; however, most patients will have tumors that... (Review)
Review
Although rare, hepatoblastoma is the most common pediatric liver tumor. Complete resection is a critical component for cure; however, most patients will have tumors that are not resected at diagnosis. For these patients, administration of neoadjuvant chemotherapy renders tumors resectable in most patients. For patients whose tumors remain unresectable after chemotherapy, liver transplantation is indicated (in the absence of active unresectable metastatic disease). In patients whose tumors remain unresectable after conventional chemotherapy, interventional techniques may serve as a promising option to reduce tumor size, decrease systemic toxicity, decrease need for liver transplantation, and increase feasibility of tumor resection.
PubMed: 28203111
DOI: 10.2147/HMER.S89997 -
Management of Unresectable Localized Pelvic Bone Sarcomas: Current Practice and Future Perspectives.Cancers May 2022Bone sarcomas (BS) are rare mesenchymal tumors usually located in the extremities and pelvis. While surgical resection is the cornerstone of curative treatment, some... (Review)
Review
Bone sarcomas (BS) are rare mesenchymal tumors usually located in the extremities and pelvis. While surgical resection is the cornerstone of curative treatment, some locally advanced tumors are deemed unresectable and hence not suitable for curative intent. This is often true for pelvic sarcoma due to anatomic complexity and proximity to vital structures, making treatment options for these tumors generally limited and not unanimous, with decisions being made on an individual basis after multidisciplinary discussion. Several studies have been published in recent years focusing on innovative treatment options for patients with locally advanced sarcoma not amenable to local surgery. The present article reviews the evidence regarding the treatment of patients with locally advanced and unresectable pelvic BS, with the goal of providing an overview of treatment options for the main BS histologic subtypes involving this anatomic area and exploring future therapeutic perspectives. The management of unresectable localized pelvic BS represents a major challenge and is hampered by the lack of comprehensive and standardized guidelines. As such, the optimal treatment needs to be individually tailored, weighing a panoply of patient- and tumor-related factors. Despite the bright prospects raised by novel therapeutic approaches, the role of each treatment option in the therapeutic armamentarium of these patients requires solid clinical evidence before becoming fully established.
PubMed: 35626150
DOI: 10.3390/cancers14102546 -
Current Oncology (Toronto, Ont.) Apr 2023Surgery is the cornerstone of treatment for retroperitoneal sarcoma (RPS). Surgery should be performed by a surgical oncologist with sub-specialization in this disease... (Review)
Review
Surgery is the cornerstone of treatment for retroperitoneal sarcoma (RPS). Surgery should be performed by a surgical oncologist with sub-specialization in this disease and in the context of a multidisciplinary team of sarcoma specialists. For primary RPS, the goal of surgery is to achieve the complete en bloc resection of the tumor along with involved organs and structures to maximize the clearance of the disease. The extent of resection also needs to consider the risk of complications. Unfortunately, the overarching challenge in primary RPS treatment is that even with optimal surgery, tumor recurrence occurs frequently. The pattern of recurrence after surgery (e.g., local versus distant) is strongly associated with the specific histologic type of RPS. Radiation and systemic therapy may improve outcomes in RPS and there is emerging data studying the benefit of non-surgical treatments in primary disease. Topics in need of further investigation include criteria for unresectability and management of locally recurrent disease. Moving forward, global collaboration among RPS specialists will be key for continuing to advance our understanding of this disease and find more effective treatments.
Topics: Humans; Neoplasm Recurrence, Local; Sarcoma; Treatment Outcome; Retroperitoneal Neoplasms; Soft Tissue Neoplasms
PubMed: 37232807
DOI: 10.3390/curroncol30050349 -
Frontiers in Oncology 2019The prognosis of stage IV gastric cancer (GC) is poor, with palliative chemotherapy remaining the main therapeutic option. Studies increasingly indicate that patients... (Review)
Review
The prognosis of stage IV gastric cancer (GC) is poor, with palliative chemotherapy remaining the main therapeutic option. Studies increasingly indicate that patients with unresectable stage IV GC, who undergo gastrectomy with radical intention after responding to several regimens of combined chemotherapy, can achieve good survival outcomes. Thus, surgery aiming at radical resection for unresectable stage IV GC after combined chemotherapy has received increasing attention in recent years. This novel therapeutic strategy was defined as conversion surgery in patients with unresectable stage IV GC and it can associate with significant improved survival when R0 resection can be achieved. Despite the recent advances in conversion surgery for patients with unresectable stage IV GC, selection criteria for combination chemotherapy regimens, indications for conversion surgery, optimal timing to surgery, and postoperative chemotherapy all remain controversial. This article reviews the current state of conversion surgery for unresectable stage IV GC.
PubMed: 31788445
DOI: 10.3389/fonc.2019.01158 -
Journal of Clinical Medicine Nov 2020With the development of systemic treatments with high response rates, including tyrosine kinase inhibitors and immune checkpoint inhibitors, some patients with... (Review)
Review
With the development of systemic treatments with high response rates, including tyrosine kinase inhibitors and immune checkpoint inhibitors, some patients with unresectable lung cancer now have a chance to undergo radical resection after primary treatment. Although there is no general consensus regarding the definition of "unresectable" in lung cancer, the term "resectable" refers to technically resectable and indicates that resection can provide a favorable prognosis to some extent. Unresectable lung cancer is typically represented by stage III and IV disease. Stage III lung cancer is a heterogeneous disease, and in some patients with technically resectable non-small cell lung cancer (NSCLC), multimodality treatments, including induction chemoradiotherapy followed by surgery, are the treatments of choice. The representative surgical intervention for unresectable stage III/IV NSCLC is salvage surgery, which refers to surgical treatment for local residual/recurrent lesions after definitive non-surgical treatment. Surgical intervention is also used for an oligometastatic stage IV NSCLC. In this review, we highlight the role of surgical intervention in patients with unresectable NSCLC, for whom an initial complete resection is technically difficult. We further describe the history of and new findings on salvage surgery for unresectable NSCLC and surgery for oligometastatic NSCLC.
PubMed: 33260352
DOI: 10.3390/jcm9123881 -
Chinese Clinical Oncology Dec 2019Asia suffers a particularly large prevalence of the world's hepatocellular carcinoma (HCC), accounting for nearly 72.5% of the newly diagnosed 609,596 cases and 72.4% of... (Review)
Review
Asia suffers a particularly large prevalence of the world's hepatocellular carcinoma (HCC), accounting for nearly 72.5% of the newly diagnosed 609,596 cases and 72.4% of the 566,269 deaths. The majority of HCC patients is diagnosed at unresectable stages in Asia despite efforts to improve availability of screening. Although the Barcelona Clinic Liver Cancer (BCLC) staging algorithm is accepted worldwide, various staging systems and guidelines have been proposed in Asian regions. Embolotherapy has been endorsed by many Asian guidelines and is the most common treatment across all stages of HCC. There are considerable discrepancies of the allocation of embolotherapy for unresectable HCC in Asia. This review will focus on the indication and contraindication, technique variances, combination regimen, and when to start, repeat or stop embolotherapy for unresectable HCC with the hope to provide insights into TACE application to patients at any HCC stage.
Topics: Carcinoma, Hepatocellular; Embolization, Therapeutic; Female; Humans; Liver Neoplasms; Male
PubMed: 31865712
DOI: 10.21037/cco.2019.11.01