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Adverse events and complications in patients with oral and oropharyngeal carcinoma treated with chemo- and radio-therapy

Umberto Romeo1*
  • 1 Sapienza University of Rome, Department of Oral Sciences and Maxillofacial Surgery, Italy

Oral and pharyngeal cancer is the seventh most common type of cancer in Europe and the 9th site of cancer death, with an estimated number of 67,000 incident cases and 26,000 deaths in 2004 (Garavello et al., 2010). The annual incidence (per 100,000 person-years) rose to 18.2 in males and 4.9 in females. According to the Italian Ministry of Health, in our country the incidence of oral and oropharyngeal carcinoma is 8.44 new cases out of 100,000 for males and 2.22 for females. Risk factors for oral and oropharyngeal carcinoma are: tobacco, high alcohol consumption, age (V-VII decade of life), family history for cancer, chronic immunosuppression and persistent HPV infection. Some Authors reported in recent years there has been an increase in the incidence of oral and oropharyngeal carcinoma in male patients under the age of 45 who are not exposed to the classic risk factors (Hussein et al., 2017). This suggests that this type of patient may represent a new entity at an epidemiological level whose risk factors and aetiology are not yet well defined. The incidence of oral and oropharyngeal carcinoma in patients under the age of 45 is increased above all in the western world. An exception is the Netherlands showing an inverse trend. The prevalence is highest in Asia and Africa, with about 30% of the population diagnosed with oral or oropharyngeal carcinoma below 45-50 years of age. South and Central America, on the other hand, show a low prevalence, with promising data deriving from Brazil (Hussein et al., 2017). In these patients the onset of carcinoma is more frequently observed in the lingual area for the female sex, especially at the level of the front 2/3 of the tongue, while for the male subjects the oropharynx is more frequently involved and in particular the base of the tongue (1/3 back and tonsils palatine). Males are more affected than females. The aetiology of oral and oropharyngeal carcinoma in patients below 45-50 years of age, although not yet clarified, would be related to the following risk factors: HPV, Genetic factors and impairment of the immune system. To confirm and underline the role of the HPV as important risk factor for the oropharyngeal carcinoma, the eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces, with respect to the previous edition, one separation with respect to the criteria for the staging of HPV-related oropharyngeal carcinomas (p16 positive) compared to those not related to HPV (p16 negative). Early stage neoplasms (stage I and II) are usually treated with surgery or radiotherapy; in advanced lesions usually, a combination of chemotherapy and radiotherapy is used, associated or not with surgical therapy, in particular, for stages III and IV. The different therapeutic treatments (surgical, chemotherapy and radiotherapy) of oropharyngeal carcinoma can lead to some adverse events (AE) and complications. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (CTCAE 2017) The early AE occurs during treatment and are mainly caused by direct damage to the tissues (mucositis, diarrhea, radiation dermatitis, etc.). The late AE occurs following treatment, even after some time, causing permanent damage to the tissues involved (xerostomia, dysgeusia, trismus, etc.). The complication, on the other hand, can identify with a new disease that appears as a consequence of a pre-existing disease (i.e. candidosis and percutaneous endoscopic gastrostomy (PEG) tube infection. There are many therapeutic strategies available today for treating oropharyngeal carcinoma. The choice of the most indicated treatment is based on the evaluation of the carcinoma stage (i.e. grade of differentiation, site, size of the primary tumour, lymph node involvement, bone involvement, possibility of obtaining adequate surgical margins and the presence or absence of metastasis) (De Felice et al., 2017). Patients with head and neck squamous cell carcinoma have three options for the treatment: surgery, chemotherapy and radiotherapy. Each of the treatments can reserve AE and complications. Adverse events and complications to surgical treatment: Cancer surgery can be directed to the removal of the primary tumour, to the surgery of lymphatic metastases of the neck or to a reconstructive surgery (microvascular free tissue). The most common surgical complications that are found are (Suh et al., 2004;Pierangeli et al., 2016;Tenore et al., 2018): - Problems with chewing and swallowing, - Gingival Reactive Lesions, - Lockjaw, - Dysarthria, - Wound infection, - Salivary fistula, - Cervical hematoma, - Failure of devices used during reconstruction (screws and osteosynthesis plates), - Partial free flap necrosis, - Total free flap necrosis (flap failure), - Delayed healing of flap donor site wound, - Necrosis of native facial or neck skin. Adverse events and complications to chemotherapy: Adverse effects may occur in the oral cavity and oropharynx, or on the whole body. At the local level, the most common AE are: oral mucositis (OM) (Figure 1), xerostomia, dysphagia, osteonecrosis of the jaws (Figure 2), pain and oedema. OM is usually accompanied by symptoms such as pain, dysgeusia and dysphagia which in severe cases lead to the inability to feed normally, forcing the patient to resort to parenteral nutrition and the inability to implement normal oral hygiene practices. Adverse events and complications to radiotherapy: Radiotherapy is employed as a primary treatment or as an adjuvant to surgery. The radiation-related complications have a tremendous impact on the quality of life. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and image-guided radiotherapy, can offer precise radiation delivery and reduce the dose to the surrounding normal tissues without compromise of target coverage. However, high doses of radiation in large areas, may result in several undesired reactions that manifest during or after the completion of therapy. Acute dermatitis (Figure 3) is the most common radio-induced side effect during treatment for head and neck cancer but the tissues most involved in radiotherapy in the Head-Neck district are the salivary glands, taste buds, mucous membranes, bones, teeth, temporomandibular joint and muscles. When the radiotherapy is carried out in the district of the pterygoid and masseter muscles, it can easily provoke their involuntary contraction with consequent trismus, characterized by difficulty in the normal opening of the mouth. Another AE is the radio-induced dental caries due to a number of factors: xerostomia, acid salivary pH, increase of cariogenic bacteria. This event can occur 2 to 10 months after the end of the radiation treatment. For this reason, topical fluoride applications, and use of fluoride-containing toothpaste should be continued permanently after radiotherapy to minimize the risk of dental caries.

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References

1. De Felice, F., De Vincentiis, M., Valentini, V., Musio, D., Mezi, S., Lo Mele, L., Terenzi, V., D'aguanno, V., Cassoni, A., Di Brino, M., Tenore, G., Bulzonetti, N., Battisti, A., Greco, A., Pompa, G., Minni, A., Romeo, U., Cortesi, E., Polimeni, A., and Tombolini, V. (2017). Follow-up program in head and neck cancer. Crit Rev Oncol Hematol 113, 151-155. 2. Garavello, W., Bertuccio, P., Levi, F., Lucchini, F., Bosetti, C., Malvezzi, M., Negri, E., and La Vecchia, C. (2010). The oral cancer epidemic in central and eastern Europe. Int J Cancer 127, 160-171. 3. Hussein, A.A., Helder, M.N., De Visscher, J.G., Leemans, C.R., Braakhuis, B.J., De Vet, H.C.W., and Forouzanfar, T. (2017). Global incidence of oral and oropharynx cancer in patients younger than 45 years versus older patients: A systematic review. Eur J Cancer 82, 115-127. 4. Pierangeli, A., Cannella, F., Scagnolari, C., Gentile, M., Sciandra, I., Antonelli, G., Ciolfi, C., Russo, C., Palaia, G., Romeo, U., and Polimeni, A. (2016). Frequent detection of high human papillomavirus DNA loads in oral potentially malignant disorders. Clin Microbiol Infect 22, 95 e99-95 e15. 5. Suh, J.D., Sercarz, J.A., Abemayor, E., Calcaterra, T.C., Rawnsley, J.D., Alam, D., and Blackwell, K.E. (2004). Analysis of outcome and complications in 400 cases of microvascular head and neck reconstruction. Arch Otolaryngol Head Neck Surg 130, 962-966. 6. Tenore, G., Mohsen, A., Pompa, G., Brauner, E., Cassoni, A., Valentini, V., Polimeni, A., and Romeo, U. (2018). Gingival Reactive Lesions in Orally Rehabilitated Patients by Free Revascularized Flap. Case Rep Dent 2018, 2474706.

Keywords: Oral Cancer (OC), OSCC (oral squamous cell carcinoma), side effects and complications, chemotherapy, Radiotheapy

Conference: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.

Presentation Type: oral presentation

Topic: Oral Diseases

Citation: Romeo U (2019). Adverse events and complications in patients with oral and oropharyngeal carcinoma treated with chemo- and radio-therapy. Front. Physiol. Conference Abstract: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine.. doi: 10.3389/conf.fphys.2019.27.00087

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Received: 27 Nov 2018; Published Online: 09 Dec 2019.

* Correspondence: Prof. Umberto Romeo, Sapienza University of Rome, Department of Oral Sciences and Maxillofacial Surgery, Rome, Lazio, 00185, Italy, marcomascitti86@hotmail.it