Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology ("stomatitis," "mucosal inflammation," "mucositis") and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis. Oral toxicities of targeted therapies often display very characteristic features which clearly differ from classic oral injuries observed with cytotoxic chemotherapy and/or radiotherapy. In addition, they frequently affect more than 20% of treated patients and can lead to a significant morbidity or permanent treatment discontinuation. Oral mucosal toxicities described in this review include mTOR inhibitor-associated stomatitis (mIAS); stomatitis, benign migratory glossitis, and osteonecrosis of the jaw associated with multi-targeted kinase inhibitors of the VEGF and PDGF receptors; mucositis induced by EGFR inhibitors (in monotherapy or in combination with head and neck radiotherapy and/or chemotherapy); hyperkeratotic lesions with BRAF inhibitors; pigmentary changes and lichenoid reactions secondary to imatinib; and more recent data on the "Osler-Weber-Rendu-like syndrome" described with the antibody-drug conjugate, TDM-1. Finally, we provide, to our knowledge, the first available structured data on oral toxicities induced by the new recently FDA- and EMA-approved monoclonal antibodies targeting PD-1. Clinical management of these targeted therapy-related oral changes is also discussed.

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Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors

https://escholarship.org/content/qt6bp7g2jf/qt6bp7g2jf.pdf?t=qamtde

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions.

Background: Though people of color (POC) are less likely to become afflicted with skin cancer, they are much more likely to die from it due to delay in detection or presentation. Very often, skin cancer is diagnosed at a more advanced stage in POC, making treatment difficult.The purpose of this research was to improve awareness regarding skin cancers in people of color by providing recommendations to clinicians and the general public for early detection and photo protection preventive measures. Methods: Data on different types of skin cancers were presented to POC. Due to limited research, there are few resources providing insights for evaluating darkly pigmented lesions in POC. Diagnostic features for different types of skin cancers were recorded and various possible risk factors were considered. Results: This study provided directions for the prevention and early detection of skin cancer in POC based on a comprehensive review of available data. Conclusions: The increased morbidity and mortality rate associated with skin cancer in POC is due to lack of awareness, diagnosis at a more advanced stage and socioeconomic barriers hindering access to care. Raising public health concerns for skin cancer prevention strategies for all people, regardless of ethnic background and socioeconomic status, is the key to timely diagnosis and treatment.

http://journal.waocp.org/article_42292_1cf9393faff2d663ee5c6b16948e9bc7.pdf

Skin Cancer Concerns in People of Color: Risk Factors and Prevention

BACKGROUND The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). METHODS Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. RESULTS Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4+ T cells (76.59% vs 52.85%; P < .05), CD8+ T cells (62.94% vs 29.76%; P < .05), and CD3+ T cells (69.72% vs 45.49%; P < .05) in an A-CCRT-P (after treatment with radiotherapy plus chemotherapy plus the probiotic combination) group. High-throughput sequencing results indicated that CCRT had obviously disturbed the intestinal diversity of patients in an A-CCRT (after treatment with radiotherapy plus chemotherapy plus a placebo) group, whereas the probiotic combination distinctly restored the microbial diversity in the A-CCRT-P group toward that of healthy people and a B-CCRT-P (before the treatment of radiotherapy plus chemotherapy plus the probiotic combination) group. CONCLUSIONS A probiotic combination significantly enhances the immune response of patients and reduces the severity of OM through modification of gut microbiota.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.31907

A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of “key species”, in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the ...

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract

With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia–Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.

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Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma

Vijay Anand Reddy

Papers

Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma