Background
Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non−immune ...checkpoint inhibitor (non‐ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited.
Methods
A comprehensive review was conducted on dermatologic toxicities associated with different classes of non‐ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta‐analyses; and case series/reports.
Results
Dermatologic toxicities were associated with several types of non‐ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non‐ICI mAbs. Immunobullous reactions were rare and a subset of non‐ICI mAbs were associated with the development of vitiligo cAEs.
Conclusion
Dermatologic toxicities of non‐ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non‐ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.
Background: Involvement of the central nervous system (CNS) by mycosis fungoides (MF) is rare; however, it portends a poor prognosis. While aggressive multimodality therapy may improve outcomes, the ...role of radiation therapy (RT) is not well defined. Objectives: We sought to explore the efficacy of RT in the management of CNS involvement by MF. Method: We retrospectively identified five patients with MF and CNS involvement who received cranial or craniospinal RT at a single institution. Patient characteristics, disease features, radiographic findings, treatments delivered, and outcome data were extracted from the electronic medical record. Results: All 5 patients had neurologic deficits at RT initiation, and 4 experienced at least a partial improvement. Of 4 patients evaluated by MRI after RT completion, 3 had complete resolution of CNS disease within the irradiated field. At the time of last follow-up, all patients had died of MF. The median time to death was 7.4 months (range 1.0–21 months) from their diagnosis with CNS involvement and 1.2 months (range 0.4–7.1 months) from the end of RT treatment. Conclusions: We observed high rates of radiographic response and palliation of neurological symptoms. Nonetheless, all patients succumbed to their disease shortly after treatment, confirming the poor prognosis of this condition. Our findings suggest that RT may play a valuable palliative role for these patients.
The ability to develop a comprehensive panel of treatment predicting factors would significantly improve our ability to stratify patients for cytotoxic or targeted therapies, and prevent patients ...receiving ineffective treatments. We have investigated if a recently developed genome-wide haploid genetic screen can be used to reveal the critical mediators of response to anticancer therapy. Pancreatic cancer is known to be highly resistant to systemic therapy. Recently epigenetic changes have been shown to be a key determinant in the maintenance of subpopulations of cancer cells with high-level resistance to cytotoxic therapy. We show that in human pancreatic cancer cell lines, treatment with the potent class I histone deacetylase inhibitor, entinostat, synergistically enhances gemcitabine-induced inhibition of cell proliferation and apoptosis. Using a genome-wide haploid genetic screen, we identified deoxycytidine kinase (DCK) as one of the genes with the highest degree of insertional enrichment following treatment with gemcitabine and entinostat; DCK is already known to be the rate-limiting activating enzyme for gemcitabine. Immunoblotting confirmed loss of DCK protein expression in the resistant KBM7 cells. CRISPR/Cas-9 inactivation of DCK in pancreatic cancer cell lines resulted in resistance to gemcitabine alone and in combination with entinostat. We have identified gemcitabine and entinostat as a potential new combination therapy in pancreatic cancer, and in this proof-of-principle study we have demonstrated that a recently developed haploid genetic screen can be used as a novel approach to identify the critical genes that determine treatment response.
OBJECTIVES:
To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk ...stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments.
DESIGN:
Secondary analysis of three annual 24-hour point-prevalence study periods.
SETTING:
The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019.
PATIENTS:
We screened all patients presenting to the emergency department and on the general wards.
MEASUREMENTS AND MAIN RESULTS:
We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points.
CONCLUSIONS:
Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.
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