Key findings:

The abstract highlights mucositis as a prevalent and painful side effect of cancer treatment, affecting the gastrointestinal tract's epithelial cells. It underscores the significance of preventive oral hygiene and stepwise treatment strategies, including oral rinses, topical anesthetics, and systemic analgesics, to manage symptoms and minimize treatment disruptions.

What is known and what is new?

Mucositis, common among cancer patients, affects the gastrointestinal tract's epithelial cells, predominantly in the oral cavity. While its debilitating nature and impact on treatment are known, the abstract emphasizes a comprehensive approach to management, highlighting preventive oral care and stepwise treatment strategies to alleviate pain and minimize treatment disruptions, potentially improving patient outcomes.

What is the implication, and what should change now?

Mucositis significantly impacts cancer patients' quality of life and treatment outcomes, often leading to treatment delays or modifications. Healthcare providers should prioritize preventive measures such as comprehensive oral care and adopt effective pain management strategies to alleviate patient suffering and ensure uninterrupted delivery of life-saving treatments, thereby improving overall treatment efficacy and patient well-being.

Oral mucositis (also known as inflammation of the oral mucosa) is a painful and debilitating side effect of cancer chemotherapy and radiotherapy (for patients with head and neck cancer).  Oral mucositis is characterized by erythema, oedema, mucosal shedding, ulceration, and pseudomembrane formation.  Severe symptoms can interrupt the delivery of treatment, increase the prolonged use of narcotics and antibiotics, increase the length of hospital stays, cause disruptions in eating (leading to the NG tube feeding), and increase the total cost of care [1-4].

Clinical features of mucositis and severity of mucositis in radiation patients are dose-dependent.  After a cumulative dose of 10–20 Gy, hyperkeratinization occurs.  After one week of therapy (>20 Gy ), patchy erythema results.  After two to three weeks of therapy (or ~30 Gy), mucosal atrophy, ulceration, oedema, and even bleeding.  Signs and symptoms persist until two to six weeks following the completion of therapy [5].

Traditionally, mucositis was believed to result from both direct and indirect toxicity to epithelial cells, interfering with the division and maturation of mucosal epithelial cells [6]. Direct mucositis was considered to be the direct damage that occurred to the rapidly dividing basal cell layers of the epithelium, resulting in clonogenic cell death, atrophy, and ulceration.  Indirect toxic effects that lead to exacerbation of mucositis include the release of inflammatory mediators (that is, cytokines), granulocytopenia, and secondary infection [7].

Oral mucositis is believed to involve five successive phases:  initiation, message generation, signaling and amplification, ulceration, and healing.  In the initiation phase, chemotherapy and radiotherapy generate reactive oxygen species (ROS), which damage cells, tissues, and blood vessels directly. This initiation leads to the next phases of message generation and signaling and amplification, in which secondary mediators of injury (such as nuclear factor kappa-B (NF-κB)) are stimulated.  This stimulation leads to the up-regulation of genes that produce pro-inflammatory cytokines—such as tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6)—which lead to additional tissue injury and apoptosis.  Simultaneously, the pro-apoptotic ceramide pathway is activated, matrix metalloproteinase is up-regulated, fibronectin is broken down, and macrophages are activated.  In the signaling and amplification phase, a series of positive feedback loops cause further up-regulation of the aforementioned inflammatory cytokines such as TNF-α and effector proteins induced in signaling pathways.  These damaging events are concentrated in the submucosa and basal epithelium, resulting in a deceptively normal clinical appearance. When the basal epithelial cell layers experience sufficient injury and death, marked ulceration is observed, accompanied by profound pain and inflammation. The diagnosis of mucositis is generally based on clinical findings [8].

Figure 1: RTOG criteria for mucositis

Dentist's Role:

Dentists are involved in treating cancer patients, due to the role of oral hygiene in the prevention of oral mucositis and systemic infection. Dentists can provide preventative treatment prior to and during cancer therapy or provide direct treatment once mucositis is established. An initial dental prophylaxis must be done several weeks before the initiation of treatment; dental treatment must be completed at least one week before therapy begins.  After the initiation of therapy, dentists must perform regular follow-up sessions.

Prevention:

With mucositis, as with all complications of cancer treatment, the goal is to prevent it from occurring. 

Oral hygiene and care- Most preventive approaches focus on oral mucositis and generally include practicing good oral hygiene and keeping the mucosal area clean, dry, and free from possible sources of infection. Clinicians can prescribe oral rinses, such as bicarbonate or saline-containing products [9].

Cryotherapy- The theory behind oral cooling of the mouth is that the resulting vasoconstriction reduces blood flow to the epithelium, reducing the amount of chemotherapeutic drugs delivered to the mucosal cells [10, 11].

Antiseptic and antimicrobials- It prevents the colonization of potentially pathogenic bacteria, fungi, and viruses and prevents or lessens the severity of oral mucositis. Povidone-iodine is an antibacterial agent that has been shown to decrease radiotherapy-induced mucositis [12, 13].

Anti-inflammatories- Benzydamine inhibits the production of effects of inflammatory cytokines such as TNF-α and also have analgesic and anesthetic properties [3, 14-16]. 

Cytokines/growth factors- Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are hematopoietic growth factors that promote local accumulation of neutrophils in the mucosa and can induce endothelial and keratinocyte proliferation.

Palifermin, a recombinant human keratinocyte growth factor, induces epithelial cell proliferation, differentiation, and migration in normal epithelial tissue.  When administered intravenously, palifermin has reduced the incidence and severity of oral mucositis in chemotherapy and stem cell transplant patients [17-20].

Parasympathomimetic- Saliva has both mucoprotective and antimicrobial effects that can prevent the incidence and severity of oral mucositis. Oral administration of pilocarpine is very useful in treating radiation-induced xerostomia. As parasympathomimetic, they increase secretion from exocrine glands (that is, sweat, salivary, lacrimal, gastric) [21, 22].

Treatment:

If mucositis does occur, the goal remains to keep the area clean and free from possible infectious sources. Therefore, oral rinses and antiviral or antifungal medications may still be used. In addition, changing all possible oral medications to IV forms to minimize patient discomfort. A bland, soft diet is recommended for oral mucositis patients.  Acidic, spicy, salty, coarse, or dry foods should be avoided completely. (Figure 1)

The main focus of mucositis treatment should be adequate management of pain and palliation of symptoms. With this in mind, the National Comprehensive Cancer Network (NCCN) Task Force on Prevention and Management of Mucositis in Cancer Care suggests a stepwise approach for the treatment of mucositis pain.

Gabapentin- Another alternative for the treatment of mucositis pain in patients with head and neck cancer who are undergoing concomitant chemotherapy and radiation is gabapentin. It can be used for the treatment of neuropathic pain.

Mucositis is a common and painful side effect of treatment for many cancer patients. Although preventive strategies and good oral hygiene are the key, the focus of treatment should be pain management. A stepwise approach is suggested based on NCCN findings. This strategy may include oral rinses, topical anaesthetics, and systemic analgesics. However, individual patient factors should be considered in the selection of appropriate pain-management strategies. 

Funding: No funding sources.

Conflict of interest: None declared.

Ethical approval: The study was approved by the Institutional Ethics Committee of Indira Gandhi Medical College, Shimla.

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