Current oncology reports
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Current oncology reports · Apr 2020
ReviewLiver Transplantation for Cholangiocarcinoma: Insights into the Prognosis and the Evolving Indications.
Cholangiocarcinoma (CCA) is a rare malignancy of the biliary ducts that can be classified as intrahepatic, perihilar, or distal based on anatomic location. Although surgical resection can be curative, complete excision with negative margins is often difficult to achieve. In patients with unresectable disease, long-term survival is rarely seen with medical therapy alone. A multimodal treatment approach, including liver transplantation (LT) for select patients with unresectable CCA, should be considered. ⋯ While currently only an approved indication for early, liver-limited, perihilar cholangiocarcinoma, promising results have been achieved for LT in localized intrahepatic disease. The absolute indication for transplant for intrahepatic tumors is currently the subject of multiple investigations. Continued advances in neoadjuvant/adjuvant therapy and better understanding of tumor biology may further augment the number of candidates for surgical therapies, with liver transplant acting as a promising tool to improve patient outcomes. Thorough consideration for any expansion in the indication for liver transplant in malignancy is necessary in order to balance patient outcomes with utilization of the scarce donor organ resources.
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Current oncology reports · Feb 2020
ReviewDashing Decades of Defeat: Long Anticipated Advances in the First-line Treatment of Extensive-Stage Small Cell Lung Cancer.
Small cell lung cancer (SCLC) is an exceptionally lethal subtype of lung cancer. For patients with extensive-stage (ES) disease, which is the majority of patients, platinum-doublet chemotherapy has been the standard of care for decades. Dozens of phase III trials have failed to improve survival over standard platinum plus etoposide. Recent results, however, have met with long-overdue success. This manuscript reviews the new standards of care for ES-SCLC. ⋯ Two recent phase III trials have shown an improvement in overall survival with concurrent immunotherapy and chemotherapy. In IMpower 133, the addition of the anti-PD-L1 antibody atezolizumab to carboplatin plus etoposide significantly improved both progression-free survival (PFS) and overall survival (OS). This was the first trial in over 30 years to improve survival. In CASPIAN, concurrent durvalumab, another anti-PD-L1 antibody, also led to an improvement in survival. While there is clearly a need to further improve outcomes, the improvement in survival with the addition of atezolizumab or durvalumab to platinum-doublet chemotherapy is a major advance. We now have new standards of care and the potential of a more meaningful benefit for patients with advanced SCLC.
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Urothelial carcinoma (UC) is a common malignancy with an urgent need for more effective and less toxic treatment strategies. Antibody-drug conjugate (ADC) represents a novel therapeutic approach, which combines the high specificity of monoclonal antibodies covalently linked with highly active cytotoxic agents. UC is an appropriate candidate for these drugs, as it expresses unique cell surface antigens that allow for specific targeting of these cells. We hereby present a review of the current literature and future perspectives of ADC treatment in early-stage and metastatic UC. ⋯ Several ADCs are in advanced stages of development and approval, such as intravesical oportuzumab monatox in BCG-refractory non-muscle invasive bladder cancer and enfortumab vedotin and sacituzumab govitecan in pretreated metastatic UC. Other agents are in earlier stages of development, including some promising anti-Her2 agents. The favorable toxicity profile of these agents led to several combination strategies, especially with checkpoint inhibitors. In light of the encouraging results presented in this review and the recent FDA approval of enfortumab vedotin, ADCs will likely be incorporated in the management of UC in the near future.
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The palliative care population is a complex and heterogeneous one. While transfusion therapy is a readily available intervention for many patients, inadequate knowledge for accurately identifying which patient subsets at end-of-life will benefit from a transfusion, along with an unclear understanding of the magnitude of attendant risks of transfusion in those receiving palliative care, complicates the risk-benefit assessment of this therapy. In this brief review, the current literature surrounding transfusion of red cells and platelets in the palliative care patient population will be reviewed and recommendations provided. ⋯ Benefits of transfusion therapy include subjective relief of fatigue and dyspnea, and improved sense of wellness, amongst other findings. However, these responses are not durable and there are currently no validated, objective metrics that correlate with symptomatic improvements. It is clear that transfusion-associated adverse reactions are underestimated in those receiving palliative care, with reaction rates similar to the general patient population. Additionally, based on the high mortality rates reported soon after transfusion, the impact of these blood components must be considered as an exacerbating or causative factor of mortality when evaluating declining condition or death. Hematinics are rarely assessed in anemic palliative care patients or, when measured, are often not corrected. The decision to transfuse palliative care patients is multifactorial, and benefits, risks, patient wishes, blood component inventories, and alternatives to transfusion should all be considered. There are many unknowns regarding transfusion in palliative care. Critical next steps for optimizing blood component therapy in this population include high-quality trials that help to identify validated measures of objective functional changes that parallel patient-reported outcomes and subsets of patients receiving end-of-life care that will most likely be positively impacted by transfusion therapy.
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Both conventional and novel approaches to early detection of ovarian cancer are reviewed in the context of new developments in our understanding of ovarian cancer biology. ⋯ While CA125 as a single value lacks adequate specificity or sensitivity for screening, large studies have shown that a 2-stage strategy which tracks CA125 change over time and prompts transvaginal ultrasound (TVS) for a small subset of women with abnormally rising biomarker values achieves adequate specificity and detects a higher fraction of early-stage disease. Sensitivity could clearly be improved in both blood tests and in imaging. Metastasis can occur from ovarian cancers too small to increase blood levels of protein antigens and a significant fraction of ovarian cancers arise from the fimbriae of fallopian tubes that cannot be imaged with TVS. Autoantibodies, miRNA, ctDNA, DNA methylation in blood, and cervical mucus might improve sensitivity of the initial phase and magnetic relaxometry and autofluorescence could improve imaging in the second phase. Enhancing the sensitivity of two-stage strategies for early detection could reduce mortality from ovarian cancer.