Kendallcruz4313
To summarize targeted therapies and immunotherapy as treatment for advanced/metastatic biliary tract cancers and discuss ongoing clinical trials.
For the first time since gemcitabine-cisplatin was set as the standard of care in first-line advanced/metastatic biliary tract cancers in the ABC-02 trial, the combination of durvalumab and gemcitabine-cisplatin has demonstrated a statistically significant improvement of median overall survival in the TOPAZ-1 phase 3 trial. The ABC-06 trial showed a significant increase of median overall survival for FOLFOX and active symptom control compared with active symptom control alone in second-line regardless of molecular and genetic alterations. However, faced with a heterogeneous cancer, patient prognosis remains poor, leaving room for new, personalized, treatment options such as targeted therapies. Efficacy of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors has been demonstrated in different phase 2 trials for previously treated intrahepatic cholangiocarcinomas harboring FGFR2 fusions. Ivosidenib increases significantly median progression-free survival in previously treated cholangiocarcinomas with isocitrate dehydrogenase-1 (IDH-1) mutation. Other targeted therapies are tested for tumors with HER2 amplifications/mutations, BRAFV600E mutations or KRASG12C mutations.
In this review, we aim to follow the changes in the treatment of these tumors, moving from very few chemotherapy options to immunotherapy and targeted therapies in the context of molecular selection of biliary tract cancers subtypes.
In this review, we aim to follow the changes in the treatment of these tumors, moving from very few chemotherapy options to immunotherapy and targeted therapies in the context of molecular selection of biliary tract cancers subtypes.
Circulating tumour DNA (ctDNA) is an appealing minimally invasive tool with significant theranostic potential. In this review, we highlighted recent studies evaluating three major applications of ctDNA in gastrointestinal malignancies.
ctDNA demonstrated a strong prognostic value in colorectal and gastroesophageal cancers in assessing minimal residual disease after radical surgery. ctDNA-guided interventional studies are ongoing.Tracking clonal dynamics with early identification of response and resistance to therapies is of particular interest in gastrointestinal cancers especially for established targeted therapies such as antiepidermal growth factor receptor (EGFR), BRAF inhibitors and immune checkpoint inhibitors.Early cancer detection via ctDNA approaches is encouraging and of particular relevance in gastrointestinal cancers in view of limited screening programmes and yet poor outcomes of metastatic patients.
Although feasible and powerful tool, the clinical utility of ctDNA to guide patients' management is challenging to demonstrate and requires further investigations in large interventional clinical trials.
Although feasible and powerful tool, the clinical utility of ctDNA to guide patients' management is challenging to demonstrate and requires further investigations in large interventional clinical trials.
Giant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more important role came into play for systemic therapy including denosumab and bisphosphonates over the last decade.
In diagnostics, focus has been on H3F3A (G34) driver mutations present in GCTB. The most frequent mutation (G34W) can be detected using immunohistochemistry and is highly specific in differentiating GCTB from other giant cell containing tumors. PD-L1 expression can be used as biological marker to predict higher recurrence risks in GCTB patients.The use of bisphosphonate-loaded bone cement is under investigation in a randomized controlled trial. A new technique consisting of percutaneous microwave ablation and bisphosphonate-loaded polymethylmethacrylate cementoplasty was proposed for unresectable (pelvic) GCTB.Increased experience with use of denosumab raised concern on elevated recurrence rates. However, conclusions of omized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab. PD-L1 could be a potential new therapy target in GCTB.
To summarize the development of modified T-cell therapies in sarcomas and discuss relevant published and ongoing clinical trials to date.
Numerous clinical trials are underway evaluating tumor-specific chimeric antigen receptor T cells and high affinity T-cell receptor (TCR)-transduced T cells in sarcomas. Notably, translocation-dependent synovial sarcoma and myxoid/round cell liposarcoma are the subject of several phase II trials evaluating TCRs targeting cancer testis antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen-A4 (MAGE A4), and response rates of up to 60% have been observed for NY-ESO-1 directed, modified T cells in synovial sarcoma. Challenges posed by modified T-cell therapy include limitations conferred by HLA-restriction, non-immunogenic tumor microenvironments (TME), aggressive lymphodepletion and immune-mediated toxicities restricting coinfusion of cytokines.
Cellular therapy to augment the adaptive immune response through delivery of modified T cells is an area of novel therapeutic development in sarcomas where a reliably expressed, ubiquitous target antigen can be identified. Therapeutic tools to improve the specificity, signaling, proliferation and persistence of modified TCRs and augment clinical responses through safe manipulation of the sarcoma TME will be necessary to harness the full potential of this approach.
Cellular therapy to augment the adaptive immune response through delivery of modified T cells is an area of novel therapeutic development in sarcomas where a reliably expressed, ubiquitous target antigen can be identified. Therapeutic tools to improve the specificity, signaling, proliferation and persistence of modified TCRs and augment clinical responses through safe manipulation of the sarcoma TME will be necessary to harness the full potential of this approach.
The objective of this article is to summarize new treatment strategies of desmoid tumors.
Desmoid tumor has an unpredictable evolution that may spontaneously regress or stabilize. A shift toward an initial frontline active surveillance has been acknowledged by experts. Surveillance monitoring should be performed frequently after the diagnosis to avoid missing a significant progression and then spaced in case of stabilization. Treatment is based on significant tumor growth or symptoms. Recent guidelines recommend commencing medical treatment. Kinase inhibitors and cytotoxic agents are the two classes of drugs where studies included progressive desmoid tumors and should be selected to guide medical practice. In a randomized trial, 2 years progression-free survival (PFS) was significantly better in the sorafenib group (81 versus 36% in the placebo group). In another randomized phase 2, 6 months PFS was 83.7% with pazopanib versus 45% with methotrexate and vinblastine. In a retrospective study, including progressive desmoid tumors, methotrexate + vinca alkaloids achieved 75 months median PFS. Cryotherapy is an alternative option in desmoid tumors with compatible locations and tumor sizes. Following medical treatment or cryotherapy failure, superficial sites represent the best indications for surgery in cases of continuous progression. learn more In the event of a contra-indication or failure of medical treatment, in locations where surgery would be mutilating and incomplete, radiotherapy is an effective option.
Active surveillance with planned imaging has become the first-line management in desmoid tumor.
Active surveillance with planned imaging has become the first-line management in desmoid tumor.
To review current knowledge and recent advances in retroperitoneal sarcoma management.
Surgery, radiotherapy, and medical treatments of retroperitoneal sarcomas should take into account the peculiarities of each histotype and the unique anatomical site. Surgery remains the mainstay of treatment and the only chance of cure for these diseases. In low-grade retroperitoneal sarcomas, like well differentiated liposarcoma, where the leading cause of death is dominated by local rather than distant relapses, treatment of the primary tumor encompasses extended surgery with multiorgan resection and evaluation of preoperative radiotherapy. Conversely, surgery is usually more conservative and without radiotherapy in those retroperitoneal sarcomas, such as leiomyosarcoma, characterized by a high risk of metastatic spread that prompted also the evaluation of neoadjuvant, histotype-driven chemotherapy. Surgery might have a role also for relapsed disease, despite long-term disease control probability declines at each recurrence. In advanced stages, anthracyclines still retain a key role and all medical treatment strategies should follow the specific chemosensitivity of each histotype to improve patient's outcomes.
The rarity and heterogeneity in biological behavior and clinical presentation of retroperitoneal sarcomas deserves a multidisciplinary and histotype-driven treatment at all stages of the disease to be performed in highly specialized centers.
The rarity and heterogeneity in biological behavior and clinical presentation of retroperitoneal sarcomas deserves a multidisciplinary and histotype-driven treatment at all stages of the disease to be performed in highly specialized centers.
Diffuse-type tenosynovial giant cell tumor (dt-TGCT) is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic, require multiple surgical procedures during their lifetime, and have reduced quality of life (QoL). Surgery is the main treatment with relapse rates ranging from 14 to 55%. The treatment strategy for patients with dt-TGCT is evolving. The purpose of this review is to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of dt-TGCT as well as related therapeutic implications.
TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumor, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as pexidatinib, imatinib, nilotinib, DCC-3014 (vimseltinib), and the monoclonal antibody RG7155 (emactuzumab).
In conclusion, D-TGCT impairs patients' QoL. The evidence that the pathogenetic loop of D-TGCT can be inhibited has changed the therapeutic armamentarium for this condition. Clinical trials of agents that target CSF1R are currently ongoing. All this new evidence should be taken into consideration within multidisciplinary management.
In conclusion, D-TGCT impairs patients' QoL. The evidence that the pathogenetic loop of D-TGCT can be inhibited has changed the therapeutic armamentarium for this condition. Clinical trials of agents that target CSF1R are currently ongoing. All this new evidence should be taken into consideration within multidisciplinary management.
