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Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention. The goal of this study was to develop a clinically viable protocol for extraoral PBMT. Monte Carlo modeling was used to predict the distribution of 850 nm light for four treatment sites, using anatomical data obtained from MRI and optical properties from the literature. Simulated incident light power density was limited to 399 mW/cm2 to ensure treatment safety and to prevent tissue temperature increase. The results reveal that total tissue thickness determines fluence rate at the oral mucosa, whereas the thickness of individual tissue layers and melanin content are of minor importance. Due to anatomical differences, the fluence rate varied greatly among patients. Despite these variations, a universal protocol was established using a median treatment time methodology. The determined median treatment times required to deliver efficacious dose between 1 and 6 J/cm2 were within 15 min. The developed PBMT protocol can be further refined using the combination of pretreatment imaging and the Monte Carlo simulation approach implemented in this study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oral mucositis (OM) remains a significant unmet need for patients being treated with standard concomitant chemoradiation (CRT) regimens for head and neck cancers (HNC). OM's pathogenesis is complex and includes both direct and indirect damage pathways. In this paper, the field is reviewed with emphasis on the initiating and sustaining role of oxidative stress on OM's pathobiology. A hypothesis is presented which suggests that based on OM's clinical and biological trajectory, mucosal damage is largely the consequence of cumulative CRT-induced biological changes overwhelming physiologic self-protective mechanisms. Furthermore, an individual's ability to mount and maintain a protective response is dependent on interacting pathways which are primarily determined by a multiplex consisting of genomics, epigenomics, and microbiomics. Effective biologic or pharmacologic OM interventions are likely to supplement or stimulate existing physiologic damage-control mechanisms. [ABSTRACT FROM AUTHOR]

Opinion Statement: Despite its history as one of the most impactful toxicities associated with cytotoxic cancer therapy, oral mucositis (OM) remains an unmet clinical need which affects hundreds of thousands of patients. Descriptions of its complex pathogenesis have provided mechanistic targets which are being exploited to develop an effective therapeutic intervention. Favorable results of recently completed clinical trials in which agents focused on interrupting the early stages of the mucositis biological cascade were assessed provide reason for optimism, not only for oral mucositis but also for halo indications which share its pathobiogenesis. [ABSTRACT FROM AUTHOR]

Toxicities associated with cancer treatment have been recognized since the first patients were treated with cytotoxic therapy and have been redescribed, discussed, categorized, and re-categorized for decades. Simultaneously, the limited success and toxicities of many cytotoxic treatment regimens necessitated the introduction of new approaches to cancer treatment which have largely been driven by advances in understanding of cancer biology. Cancer therapies have continuously evolved to include novel radiation delivery technologies, an expanding range of cytotoxic agents, and new targeted drugs and immunotherapies [[1]-[4]]. Spending for oncology drug development led all other clinical indications last year and this quest for advanced therapeutics will continue, catalyzed by improvement in patient outcomes and the vast commercial potential of successful cancer treatments [[7]]. [Extracted from the article]

An editorial is presented on data sharing from control cohorts in pharma-sponsored clinical trials. Topics include advances in prevention and management of old and new toxicities beginning with patient data for identifying the nature, severity, and frequency of potential toxicities; and data collection showing activity trackers, online food diaries, online cognitive test batteries, and weighing scales with a bioelectrical impedance analysis system.

Goals Oral mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n=3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced oral mucositis. Materials and methods We collected blood, saliva, and oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day -10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of oral mucositis was determined using the Oral Mucositis Index. Severity of pain due to oral mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Main results Mean mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Conclusions Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced mucositis. [ABSTRACT FROM AUTHOR]

Alimentary tract (AT) mucositis is a serious problem complicating cancer treatment, however, its pathobiology remains incompletely understood. Nuclear factor-κB (NF-κB) and pro-inflammatory cytokines are considered to have important roles in its development. This has been previously demonstrated in different sites of the AT following administration of irinotecan in an animal model using the Dark Agouti rat. The aim of the present study was to determine whether the changes that occur in the AT are affected by the type of mucotoxic drug. Female DA rats were given a single dose of either methotrexate (1.5 mg/kg intramuscularly) or 5-fluorouracil (150 mg/kg intraperitoneally). Rats were killed at 30, 60, 90 min, 2, 6, 12, 24, 48 and 72 h. Control rats received no treatment. Samples of oral mucosa, jejunum and colon were collected. Haematoxylin and eosin stained sections were examined with respect to histological evidence of damage and standard immunohistochemical techniques were used to demonstrate tissue expression of NF-κB, TNF, IL-1β and IL-6. Both MTX and 5-FU administration caused histological evidence of tissue damage in the AT as well as changes in tissue expression of NF-κB and specific pro-inflammatory cytokines. This study, however, demonstrated that there were differences in the timing of histological changes as well as the timing and intensity of pro-inflammatory cytokine tissue expression caused by the different drugs. The results from this study suggest that there are differences in the mucositis pathobiology caused by different drugs. This may have important ramifications for the management of mucositis particularly with respect to the development of treatment regimens for mucositis. Further investigations are required to determine the exact pathways that lead to damage caused by the different drugs. [ABSTRACT FROM AUTHOR]

The pathobiology of alimentary tract (AT) mucositis is complex and there is limited information about the events which lead to the mucosal damage that occurs during cancer treatment. Various transcription factors and proinflammatory cytokines are thought to play important roles in pathogenesis of mucositis. The aim of this study was to determine the expression of nuclear factor-κB (NF-κB), tumor necrosis factor (TNF) and interleukins-1β (IL-1β) and -6 (IL-6) in the AT following the administration of the chemotherapeutic agent irinotecan. Eighty-one female dark Agouti rats were assigned to either control or experimental groups according to a specific time point. Following administration of irinotecan, rats were monitored for the development of diarrhoea. The rats were killed at times ranging from 30 min to 72 h after administration of irinotecan. Oral mucosa, jejunum and colon were collected and standard immunohistochemical techniques were used to identify NF-κB, TNF, IL-1β and IL-6 within the tissues. Sections were also stained with haematoxylin and eosin for histological examination. Irinotecan caused mild to moderate diarrhoea in a proportion of the rats that received the drug. Altered histological features of all tissues from rats administered irinotecan were observed which included epithelial atrophy in the oral mucosa, reduction of villus height and crypt length in the jejunum and a reduction in crypt length in the colon. Tissue staining for NF-κB, TNF and IL-1β and IL-6 peaked at between 2 and 12 h in the tissues examined. This is the first study to demonstrate histological and immunohistochemical evidence of changes occurring concurrently in different sites of the AT following chemotherapy. The results of the study provide further evidence for the role of NF-κB and associated pro-inflammatory cytokines in the pathobiology of AT mucositis. The presence of these factors in tissues from different sites of the AT also suggests that there may be a common pathway along the entire AT causing mucositis following irinotecan administration. [ABSTRACT FROM AUTHOR]

Oral and gastrointestinal mucositis is a toxicity of many forms of radiotherapy and chemotherapy. It has a significant impact on health, quality of life and economic outcomes that are associated with treatment. It also indirectly affects the success of antineoplastic therapy by limiting the ability of patients to tolerate optimal tumoricidal treatment. The complex pathogenesis of mucositis has only recently been appreciated and reflects the dynamic interactions of all of the cell and tissue types that comprise the epithelium and submucosa. The identification of the molecular events that lead to treatment-induced mucosal injury has provided targets for mechanistically based interventions to prevent and treat mucositis. [ABSTRACT FROM AUTHOR]

This article examines the use of palifermin in myelotoxic therapy-induced oral mucositis. Oral mucositis is among the common toxicities of myeloablative regimens used for conditioning prior to hematopoietic stem cell transplantation. Patients with mucositis have more days of opioid and antibacterial use, more days of fever and use of total parenteral nutrition, than do patients without the condition. Palifermin is the first approved drug that effectively modulates the course and duration of the condition. Its cytoprotective activities relating to DNA strand breaks and inhibition of apoptosis are likely to contribute to its efficacy.