European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations). To improve response rates and to overcome resistance, novel second- and third-generation immuno-oncology drugs are currently evaluated in ongoing phase I/II trials (either alone or in combination) including novel inhibitory compounds (e.g. TIM-3, VISTA, LAG-3, IDO, KIR) and newly developed co-stimulatory antibodies (e.g. CD40, GITR, OX40, CD137, ICOS). ⋯ Although initial phase I/II clinical trials of agonistic and novel antagonistic drugs have shown highly promising results in the absence of disabling toxicity, both in single-agent studies and in combination with chemotherapy or other immune system targeting drugs; however, numerous questions remain about dose, schedule, route of administration and formulation as well as identifying the appropriate patient populations. In our view, with such a wealth of potential mechanisms of action and with the ability to fine-tune monoclonal antibody structure and function to suit particular requirements, the second and third wave of immuno-oncology drugs are likely to provide rapid advances with new combinations of novel immunotherapy (especially co-stimulatory antibodies). Here, we will review the mechanisms of action and the clinical data of these new antibodies and discuss the major issues facing this rapidly evolving field.
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Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients diagnosed with MM is not represented in these trials. ⋯ Over half of the patients evaluated for systemic treatment of MM are not represented in phase III registration immunotherapy trials. The data reveal a huge knowledge gap regarding the usefulness of new immunotherapies in the 'real-world' patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.
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Review Meta Analysis
Lymph node yield after rectal resection in patients treated with neoadjuvant radiation for rectal cancer: A systematic review and meta-analysis.
The lymph node status represents a major prognostic factor in colorectal cancer. However, it was demonstrated that neoadjuvant chemoradiotherapy (CRT) decreases the numbers of lymph nodes in the specimen. Several studies describe less than 12 lymph nodes in the resected specimen of rectal cancer patients after neoadjuvant radiation. This meta-analysis quantifies the influence of neoadjuvant CRT or radiotherapy (RT) only on the lymph node yield in rectal cancer patients. ⋯ Neoadjuvant CRT or RT only in rectal cancer patients leads to a decrease in lymph node harvest of approximately four and two lymph nodes, respectively. We therefore stress the importance of intensifying all efforts from involved subspecialities (i.e. surgeons and pathologists) to reach the benchmark harvest of 12 resected lymph nodes according to current guidelines.
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MANIFESTO-CALL TO ACTION.
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Posttreatment detection of recurrence may lead to salvage treatment and prognostic prediction in patients with head and neck squamous cell carcinoma (HNSCC). We evaluated the diagnostic and prognostic values of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) after definitive treatment of HNSCC. ⋯ Posttreatment 18F-FDG PET/CT surveillance helps to properly detect recurrence and to predict the survival following treatment of HNSCC.