Oral Cancer and Complications of Cancer Therapies _ _____________________________________________
immunologically compromised. Oral candidiasis has different manifestations and degrees of severity. Angular cheilitis occurs when these organisms infect the commissures of the lips and the surrounding skin. The affected areas are sore and can crack and bleed easily. Treatment with a topical antifungal (such as miconazole) that is usually successful in the immunocompetent patient may not be successful in patients with cancer. Pseudomembranous candidiasis features white to yellow-white raised plaques that may occur on any oral surface. These plaques may be wiped away from the underlying mucosal sur- face and an erythematous base will be revealed. This fungal infection can spread to the pharynx and esophagus by direct extension. Organisms that infect an area of mucositis have a portal for hematogenous dissemination and cause invasive candidiasis. Treatment with the swish-and-swallow regimen of nystatin may not work as well, or as quickly, in the immu- nocompromised patient [72]. Systemic antifungals, such as fluconazole, caspofungin, micafungin, anidulafungin, or lipid formulation of amphotericin B, may be necessary [82]. Another antifungal medication, voriconazole, is also available, but the side effects associated with its use are more severe and it offers little advantage over fluconazole as initial therapy [82]. The resistance of fungal organisms to these medications is becom- ing an increasing problem. Systemic antifungal medications should be prescribed with care, as they can interact with many other medications to produce serious side effects. Patients with impaired liver function may be unable to take these medica- tions due to the risk for potentially fatal hepatotoxicity [51]. Prosthetic appliances that are made of acrylic should also be treated to destroy any inhabitant fungal organisms [82]. Some patients (e.g., neutropenic patients) benefit from a course of prophylactic antifungal medication (in recommended order: fluconazole, posaconazole, caspofungin) during chemotherapy [82]. Itraconazole is available for prophylaxis but is not rec- ommended, except in the instance of fluconazole-refractory disease [82]. Isavuconazole, an expanded-spectrum antifungal approved in 2015, has excellent in vitro activity against Candida species [82; 83]. Viral Infections The activation of herpes simplex virus or varicella zoster virus (shingles) is a common occurrence in immunocompromised patients [84]. These viruses reside and lie dormant in the gan- glia of neurons until a triggering event or stressor stimulates their activation. In immunocompromised patients, these viral infections are more susceptible to systemic or organ dissemina- tion [85]. Because they reside in the actual nerve, these viruses cannot be destroyed by any medical procedure. Intraoral herpetic lesions may appear as large ulcerative areas and can resemble mucositis. Only a culture for this virus dis- tinguishes between the two. When varicella zoster manifests facially, it follows the sensory distribution of either the right or left trigeminal nerve. The affected areas are much larger than those infected with the herpes simplex virus, and there is a
commensurate increase in pain. The skin is most commonly involved, although the mandibular division of the trigeminal nerve may allow for an intraoral manifestation. Analgesic and antiviral medications will decrease the symptoms associated with the outbreak. The ultimate goal of therapy in cases of post chemotherapy varicella zoster is to prevent or control systemic and/or organ dissemination, as the majority of mortalities related to varicella zoster are attributable to these complications [85]. Acyclovir is recommended, especially for immunosuppressed patients [85; 86; 87; 88]. Valacyclovir or famciclovir may also be used [86; 87; 88]. Brivudin is contrain- dicated for patients receiving chemotherapy as the risk of fatal interaction with certain chemotherapeutic agents has been established [85; 86; 88]. Brivudin is not currently available in the United States [51]. Unlike the healing pattern for the her- pes simplex virus, varicella zoster may leave scars upon healing and may have painful exacerbations of posthealing neuralgia. If the ophthalmic branch of the trigeminal nerve is involved, an ophthalmologist should be consulted as involvement of the cornea may lead to corneal scarring and blindness [85].
MEDICATION-RELATED OSTEONECROSIS OF THE JAW
The use of large doses of IV bisphosphonates, as is common among patients with multiple myeloma or metastatic breast cancer, has been linked to the development of jaw osteone- crosis [89]. This phenomenon was previously referred to as bisphosphonate-related osteonecrosis of the jaw. However, the preferred term is now medication-related osteonecrosis of the jaw (MRONJ), which is favored due to the rise in osteonecrosis cases associated with other antiresorptive (denosumab) and antiangiogenic therapies [90; 91]. MRONJ is diagnosed by the presence of three characteristics [90]: • Current or previous treatment with antiresorptive or antiangiogenic agents • Exposed bone or bone that can be probed through an intraoral or extraoral fistula(e) in the maxillofacial region that has persisted for more than eight weeks • No history of radiation to the jaws or obvious metastatic disease to the jaws The risk of developing MRONJ increases with extended use of the medications. According to one meta-analysis, the majority of cases (60%) were precipitated by tooth extraction or oral surgery, which may involve trauma to the alveolar bone during the procedure as well as complications arising during recovery [89; 92; 93]. Among patients with jaw osteonecrosis who have not had oral surgery or tooth extraction, the use of dental pros- theses or other oral problems are often present [94]. The results of one study suggest that the accurate diagnosis of MRONJ at the time of extraction is critical, and that an additional category of MRONJ that encompasses cases of bony necrosis found in the extraction socket during tooth extraction procedures may be needed. The study results also suggest that the routine
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