THE MULTIDISCIPLINARY TEAM APPROACH

It can be challenging to manage patients who have been diagnosed with malignant nasal tumors, undergone tumor debulking in a low-volume service, and later been referred for further treatment at a tertiary cancer center. Although infrequent, such management may reduce the chance of cure and confer unjustified detriment to the patient. According to the guidelines of the National Comprehensive Cancer Network and the European Society for Medical Oncology, MDTs are equal-level structures that include clinicians who play various roles, and have different areas of specialization and degrees of expertise. An MDT thus enables the creation of a network in which the patient is at the center of the decision-making process.6–8 At presentation, the focus is to determine the stage of the disease (early, intermediate, or locally-advanced) and the role of surgery in its management. The objective is to make a correct diagnosis and provide patients with the best possible treatment.9

The head and neck cancer MDT includes physicians and paramedical staff from multiple disciplines.10 This tumor board is directed toward attaining a comprehensive evaluation of cancer patients from different points of view.11 Tumor board discussions incorporate information based on the fields of expertise, experience, and knowledge of all the participating specialists, including surgery, medical oncology, radiation oncology, radiology, nuclear medicine, and pathology.12 The entire team is thus able to arrive at a wide-ranging assessment of a patient’s case, at one time, rather than over the course of several days and a number of separate visits with specialists.9,12


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As regards melanomas, in comparison to conventional care, the MDT approach has been shown to reduce healthcare costs by optimizing treatments and reducing treatment-associated adverse events.13 In the best settings, an MDT workup will ensure accurate assessment, evidence-based decision-making, and the most advantageous treatment planning and delivery

THE ROLE OF THE MULTIDISCIPLINARY TEAM WORKOUT

Studies in non-small-cell lung cancer and breast cancer showed that MDTs led to changing treatment decisions in half of the patients, and eventually improved the survival of those individuals.15,16

A number of studies have reported outcomes from the MDT approach in head and neck cancers. A prospective study by Wheless et al17 evaluated the tumor characteristics and treatment plans for 120 patients who were presented to MDT meetings of the head and neck tumor board in a tertiary academic hospital, 84 with malignant and 36 with benign tumors. The multidisciplinary head and neck tumor board conferences were attended by multiple (3 to 5) head and neck surgeons, a medical oncologist, and a radiation oncologist. When needed, representatives of other specialties were also present (eg, neurosurgery, plastic surgery, pathology, radiology; dental, oral and maxillofacial surgery, and social work). Compared to pre-conference decisions, the board’s results showed changes in tumor diagnoses, disease stage, or treatment plans in about 27% of the studied cases. Changes in treatment were significantly more common in cases of malignancy, occurring for 24% of patients versus 6% of those with benign tumors. Such changes were largely due to escalations in management related to multimodality care. Approximately 7% of these patients required a further diagnostic work-up before definitive treatment planning could advance.17

Another study that examined the role of the MDT approach in treatment decision making in head and neck cancers analyzed the retrospective data of 781 head and neck cancer patients.9 Staging or restaging by imaging, pathology, or immunohistochemical or molecular analyses was deemed necessary for 49% of the patients.9 Immediately following MDT evaluation, diagnoses were changed in 3% of the patients without any further need for additional diagnostic investigations. Treatment plans were modified for 10% of the patients. Notably, restaging was required more for those with rare, rather than common cancer types (60% vs 43%).9

Compared to patients who are managed by one physician at a time, MDT-managed cancer patients have better survival outcomes18 and shorter wait times before obtaining consultations with other experts or securing treatment.19 Moreover, they benefit from a more vigorous treatment decision making process because they have rapid access to several expert opinions.20

One large-scale British study compared the outcomes of head and neck cancer patients with and without an MDT approach during two time periods: 1996–1997 (556 patients) and 1999–2000 (727 patients). Patients assessed by an MDT exhibited improved survival (1997: P=0.1; 2000: hazard ratio 0.7, P=0.02). This suggests a correlation between patient care in a multidisciplinary clinic and patient survival.18

Ganti et al analyzed SNMM patients in a large national database to better understand treatment modalities applied and approaches taken with these individuals.3 In a univariate analysis, the study found that, due to the aggressiveness of the disease, a significant predictor of survival was the time between an SNMM diagnosis and initiation of treatment. These data emphasize the importance of fast, multidisciplinary discussion, staging, and treatment decision-making to improve survival.3

Taken together, the accumulating data on the treatment of head and neck cancer, especially the less common entities, indicate that the MDT approach is required for initial management. This allows for better definition of patient stage and adjusting the treatment plan, accordingly.9

THE AUTHORS’ PERSPECTIVE ON IMPLEMENTING THE MULTIDISCIPLINARY APPROACH

At our tertiary academic head and neck center, we conduct two MDT meetings weekly to discuss head and neck cancer and skull base tumors. The head and neck tumor board is comprised of head and neck surgeons, a medical oncologist, a radiation oncologist, a radiologist, a nuclear imaging specialist, a reconstructive surgeon, and a maxillofacial surgeon. The skull base tumor board is complemented by a neurosurgical team. The aim of these meetings is, first and foremost, to determine the best treatments for patients. In addition, they have educational value.

The role of each member of the MDT is defined and known, and the opinions of the surgeons and oncologists have equal weight regarding the best course of treatment. All verdicts are made by a joint decision.

THE MOLECULAR PROFILE OF SNMM

Considerable variation exists in the genetic alterations within the subtypes of melanoma, such as cutaneous, mucosal, and uveal.21 The majority of skin melanomas show an increased number of BRAF mutations, particularly BRAFV600E. On the other hand, a greater number of KIT gene alterations in SNMM and a complete lack of BRAFV600E alterations have been demonstrated.22–24

According to various scientific studies, the somatic oncogenic mutations that characterize SNMM are as follows: KIT, 0–40%; NRAS, 10–50%; and BRAF, 0–10%.25,26 In all tumors obtained from 17 mucosal melanoma patients, fluorescent in-situ hybridization assays showed amplification of the Ras-responsive element binding protein 1 (RREB1) gene in chromosome 6p25. The loss of proto-oncogene MYB, and the cell cycle regulator, cyclin D1 (CCND1) was reported in 76% and 15% of patients with mucosal tumors, respectively.25,27 The absence of the tumor suppressor genes PTEN and p16 was observed in SNMM patients as well, though no alterations were seen in PIK3CA, which is commonly associated with the loss of PTEN.28 Inhibition of expression or complete loss of PTEN was observed in about 40% of the patients, which compares with inhibition of p16 in 50%.25 Furthermore, the overexpression of pAkt and pERK due to alterations of multiple proteins in this signaling cascade resulted in the combined activation of PI3K/Akt and RAS-MAPK signaling pathways.24,25 High levels of pAkt1, which are frequently seen in SNMM patients, can serve as individual prognostic markers.29 Moreover, in non-metastatic BRAFV600E//Cdkn2aNull mouse, overexpression of pAkt1 was shown to be responsible for lung and brain metastasis, which gives further insight into molecular mechanisms driving melanoma progression.30 The identification and characterization of these mutations are essential as they provide potential targeting opportunities for systemic therapy. Inhibition of the effectors in the aforementioned signaling pathways will aid in the development of effective forms of therapy tailored for SNMM patients.

From an epigenetic standpoint, SNMM is known to have a specific pattern of chromosomal alterations, which are absent in cutaneous and uveal melanoma.31 In tumors obtained from SNMM patients, 100%, 93%, and 57% gains have been reported in chromosome arms 1q, 6p, and 8q, respectively. Furthermore, ploidy analysis showed significant clear and high copy gains in 75% of triploid and tetraploid tumors.31,32 Another aspect of SNMM is the high frequency of telomerase reverse transcriptase promoter mutations, which has been observed in 8% of SNMM patients. This results in higher transcriptional activity and an increased number of driver mutations.33 The current clinical significance of these alterations is unknown. However, they can facilitate the characterization of tumors and may eventually serve as therapeutic targets.

The identification of the mitochondrial expression profile in mucosal melanomas paved the way for the development of new mitochondrial biomarkers which could be utilized as potential targets for treating this disease.34 The overexpression mitochondrial biomarkers like antimitochondrial fission protein 1 (FIS1) and mitofusin‐2 (MFN2) has been observed in sinonasal melanoma patients. The former resulted in higher rates of vascular invasion in mucosal melanomas and the latter showed higher rates of distant metastasis, and both are responsible for reducing overall survival rates.35,36

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