Application of big data analyses to compare the impact of oral and gastrointestinal mucositis on risks and outcomes of febrile neutropenia and septicemia among patients hospitalized for the treatment of leukemia or multiple myeloma.

PURPOSE: Oral ulcerative mucositis (UM) and gastrointestinal mucositis (GIM) have been associated with increased likelihood of systemic infection (bacteremia and sepsis) in patients being treated for hematological malignancies. To better define and contrast differences between UM and GIM, we utilized the United States 2017 National Inpatient Sample and analyzed patients hospitalized for the treatment of multiple myeloma (MM) or leukemia. METHODS: We utilized generalized linear models to assess the association between adverse events-UM and GIM-among hospitalized MM or leukemia patients and the outcome of febrile neutropenia (FN), septicemia, burden of illness, and mortality. RESULTS: Of 71,780 hospitalized leukemia patients, 1255 had UM and 100 GIM. Of 113,915 MM patients, 1065 manifested UM and 230 had GIM. In an adjusted analysis, UM was significantly associated with increased risk of FN in both the leukemia (aOR = 2.87, 95% CI = 2.09-3.92) and MM cohorts (aOR = 4.96, 95% CI = 3.22-7.66). Contrastingly, UM had no effect on the risk of septicemia in either group. Likewise, GIM significantly increased the odds of FN in both leukemia (aOR = 2.81, 95% CI = 1.35-5.88) and MM (aOR = 3.75, 95% CI = 1.51-9.31) patients. Similar findings were noted when we restricted our analysis to recipients of high-dose condition regimens in preparation for hematopoietic stem-cell transplant. UM and GIM were consistently associated with higher burden of illness in all the cohorts. CONCLUSION: This first use of big data provided an effective platform to assess the risks, outcomes, and cost of care of cancer treatment-related toxicities in patients hospitalized for the management of hematologic malignancies

Using real world data to advance the provision of supportive cancer care: Mucositis as a case study

Purpose of review: For decades, clinical decision making and practice has been largely informed by data generated through randomized clinical trials (RCTs). By design, RCTs are highly restricted in both scope and scale, resulting in narrow indications and iterative advances in clinical practice. With the transition to electronic health records, there are now endless opportunities to utilize these ‘real world’ data (RWD) to make more substantive advances in our understanding that are, by nature, more applicable to reality. This review discusses the current paradigm of using big data to advance and inform the provision of supportive cancer care, using mucositis as a case study. Recent findings: Global efforts to synthesize RWD in cancer have almost exclusively focused on tumor classification and treatment efficacy, leveraging on routine tumor pathology and binary response outcomes. In contrast, clinical notes and billing codes are not as applicable to treatment side effects which require integration of both clinical and biological data, as well as patient-reported outcomes. Summary: Cancer treatment-induced toxicities are heterogeneous and complex, and as such, the use of RWD to better understand their etiology and interaction is challenging. Multidisciplinary cooperation and leadership are needed to improve data collection and governance to ensure the right data is accessible and reliable.Hannah R. Wardill, Steve T. Sonis, and Nicole M.A. Blijleven

Local and systemic pathogenesis and consequences of regimen-induced inflammatory responses in patients with head and neck cancer receiving chemoradiation

Treatment-related toxicities are common among patients with head and neck cancer, leading to poor clinical outcomes, reduced quality of life, and increased use of healthcare resources. Over the last decade, much has been learned about the pathogenesis of cancer regimen-related toxicities. Historically, toxicities were separated into those associated with tissue injury and those with behavioural or systemic changes. However, it is now clear that tissue-specific damage such as mucositis, dermatitis, or fibrosis is no longer the sole consequence of direct clonogenic cell death, and a relationship between toxicities that results in their presentation as symptom clusters has been documented and attributed to a common underlying pathobiology. In addition, the finding that patients commonly develop toxicities representing tissue injury outside radiation fields and side effects such as fatigue or cognitive dysfunction suggests the generation of systemic as well as local mediators. As a consequence, it might be appropriate to consider toxicity syndromes, rather than the traditional approach, in which each side effect was considered as an autonomous entity. In this paper, we propose a biologically based explanation which forms the basis for the diverse constellation of toxicities seen in response to current regimens used to treat cancers of the head and neck

Antimicrobial therapy to prevent or treat oral mucositis.

Item does not contain fulltextOral mucositis represents a significant source of morbidity after chemotherapy and radiation therapy. Since infection may have an important role in the pathophysiology of oral mucositis, several antimicrobial agents have been investigated for their efficacy in preventing and treating this disease. We sought to establish the weight of evidence for antimicrobial treatment and identified 31 prospectively designed clinical trials of which 13 reported some benefit and 15 did not. No clear pattern was identified regarding patient type, cancer treatment, or type of antimicrobial agent used, and inconsistent assessment of oral mucositis made comparison of outcomes difficult. Newer drugs, such as the topical antimicrobial peptide iseganan HCl initially showed promise in reducing mucositis and the related oral pain but the results of a phase 3 trial were disappointing and the line of enquiry was abandoned altogether. Hence, there is a need to better understand the role of the microflora in the cause of oral mucositis if an antimicrobial agent for prevention and treatment of this disease is to be developed

Assessment of oral mucositis in clinical trials: Impact of training on evaluators in a multi-centre trial

In the assessment of mucositis, the inter-evaluator variability needs to be minimised and would likely to be best accomplished by training. The aim of this study was to evaluate the effect of training on concordance of evaluators in scoring oral mucositis. The evaluators were informed about the pathobiology and clinical appearance of mucositis and were trained in scoring mucositis according the Oral Mucositis Assessment Scale (OMAS). The effect of the training was evaluated by a pre- and post-training test. Each test consisted of 15 slides depicting oral mucositis. The pre- and post-training scores were compared to the reference standard. During 8 months at 6 meetings, 65 evaluators were trained. The mean percentage correctly scored slides according the OMAS increased significantly between the pre- and post-training test (P<0.001). Training evaluators in scoring oral mucositis has a significant improvement on the outcome of mucositis assessment

Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients

Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our investigation identified a substantial number of LLLT-activated pathways that have been strongly associated with negative tumor outcomes including proliferation, invasion, angiogenesis, metastases and cancer-treatment resistance. In light of these findings, we suggest an investigational strategy to assure that LLLT’s anti-mucositis efficacy is independent of its possible potential to enhance threatening tumor behaviors. Included are appropriate pre-clinical modeling, short- and long-term follow-up of LLLT-treated patients, and the requirement for consistency of LLLT parameters

The effectiveness of commonly used mouthwashes for the prevention of chemotherapy-induced oral mucositis: a systematic review.

Contains fulltext : 49764.pdf (publisher's version ) (Closed access)Daily chlorhexidine mouthwash is often recommended for preventing chemotherapy-induced oral mucositis. Povidone-iodine, NaCl 0.9%, water salt soda solution and chamomile mouthwash are also recommended. However, the effectiveness of these mouthwashes is unclear. Therefore, we performed a systematic review to assess the effectiveness of mouthwashes in preventing and ameliorating chemotherapy-induced oral mucositis. Based on study quality, three out of five randomized controlled trials were included in a meta-analysis. The results failed to detect any beneficial effects of chlorhexidine as compared with sterile water, or NaCl 0.9%. Patients complained about negative side-effects of chlorhexidine, including teeth discoloration and alteration of taste in two of the five studies on chlorhexidine. The severity of oral mucositis was shown to be reduced by 30% using a povidone-iodine mouthwash as compared with sterile water in a single randomized controlled trial. These results do not support the use of chlorhexidine mouthwash to prevent oral mucositis