Head And Neck Mucosal Melanoma Research Articles

Curative carbon ion radiotherapy in a head and neck mucosal melanoma series: Facing the future within multidisciplinarity

PurposeTo evaluate efficacy and toxicity of carbon ion radiotherapy (CIRT) in locally advanced head and neck mucosal melanoma (HNMM) patients treated at our Institute. Materials and MethodsBetween June 2013 and June 2020, 40 HNMM patients were treated with CIRT. Prescription dose was 65.6-68.8 Gy relative biological effectiveness [RBE] in 16 fractions. Twelve (30%) patients received only biopsy, 28 (70%) surgical resection before CIRT. Immunotherapy was administered before and/or after CIRT in 45% of patients, mainly for distant progression (89%). ResultsMedian follow-up was 18 months. 2-year Local Relapse Free Survival (LRFS), Overall Survival (OS), Progression Free Survival (PFS) and Distant Metastasis Free Survival (DMFS) were 84.5%, 58.6%, 33.2% and 37.3%, respectively. At univariate analysis, LRFS was significantly better for non-recurrent status, < 2 surgeries before CIRT and treatment started < 9 months from the initial diagnosis, with no significant differences for operated versus unresected patients. After relapse, immunotherapy provided longer median OS (17 months vs 3.6, p-value<0.001). Late toxicity ≥ G3 (graded with CTCAE 5.0 scale) was reported in 10% of patients. ConclusionCIRT in advanced HNMM patients is safe and locally effective. Prospective trials are warranted to assess the role of targeted/immune- systemic therapy to improve OS.

Safety of immune checkpoint inhibitors after proton beam therapy in head and neck mucosal melanoma: a case series.

Proton beam therapy (PBT) has shown promising efficacy in treating locally advanced head and neck mucosal melanoma despite its poor prognosis. Although PBT may improve the efficacy of subsequent immune checkpoint inhibitors (ICIs), the safety of ICIs in patients who have previously received PBT has not been established. Hence, this study evaluated the safety of ICIs in patients who had recurrent mucosal melanoma after PBT. Between April 2013 and June 2022, we retrospectively reviewed the medical records of patients diagnosed with cutaneous or mucosal melanoma at the National Cancer Center Hospital East. Seven patients were treated with ICIs after their head and neck mucosal melanoma (HNMM) recurred after PBT. Four of the seven patients experienced grade immune-related adverse events (irAEs). Due to irAE in the irradiation field, two patients had grade 3 hypopituitarism. Other grade 3 or higher irAEs included an increase in serum alanine aminotransferase in two patients and gastritis in one, and two patients discontinued ICI due to the irAEs. All irAEs were resolved with appropriate management. Although administering ICIs after PBT may increase the risk of irAEs, especially in the irradiation field, they appear manageable. These findings could help in the development of a treatment strategy for locally advanced HNMM that includes PBT and subsequent ICIs.

Impact of Treatment Delay in Head and Neck Mucosal Melanoma on Overall Patient Survival.

Objectives Head and neck mucosal melanoma (HNMM) is a rare malignancy with high mortality. This study evaluates the impact of treatment delays on overall survival in HNMM. Design/Setting/Participants A retrospective review of patients with surgically managed HNMM treated with adjuvant radiation was performed from the 2004-2016 National Cancer Database. Main Outcome Measures Durations of diagnosis-to-treatment initiation (DTI), surgery-to-radiotherapy initiation (SRT), duration of radiotherapy (RTD), surgery-to-immunotherapy initiation (SIT), diagnosis-to-treatment end (DTE), and total treatment package (TTP) were calculated. Results A total of 1,011 patients (50.7% female, 90.5% Caucasian) met inclusion criteria. Median DTI, SRT, RTD, SIT, DTE, and TTP were 30, 49, 41, 102, 119, and 87 days, respectively. Only longer DTE was associated with decreased mortality (hazard ratio, 0.720; 95% confidence interval, 0.536-0.965; p = 0.028). Conclusion DTI, SRT, RTD, SIT, and TTP do not significantly affect overall survival in patients with HNMM who undergo surgery and adjuvant radiation. Longer DTE is associated with improved survival in this population. Level of Evidence 4.

Efficacy of immune checkpoint inhibitor treatment for head and neck mucosal melanoma recurrence in patients treated with carbon-ion radiotherapy.

Carbon-ion radiotherapy (C-ion RT) is effective for head and neck mucosal melanoma (HN-MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN-MM are insufficient. To analyze the efficacy and safety of ICI salvage therapy in patients with HN-MM recurrence after C-ion RT. This retrospective study analyzed the medical records of 52 patients with HN-MM treated with C-ion RT between 2012 and 2020. A dose of 57.6 or 64.0 Gy (relative biological effectiveness) was provided in 16 fractions. The primary endpoint was 3-year overall survival (OS) rate. The median follow-up time was 26.8 months for all patients. A total of 29 patients had local recurrence or distant metastasis, and 16 patients who received ICI therapy. The 3-year OS rate in the ICI group (n = 16) and best supportive care group (n = 13) were 53.8% and 0.0%, respectively (p = 0.837); the difference was not statistically significant. There were no deaths after 1 year among patients who underwent ICI therapy. No adverse events associated with C-ion RT were related to or exacerbated by ICI. ICI salvage therapy is effective and safe for patients with HN-MM recurrence after C-ion RT.

Head and neck mucosal melanoma: radiological considerations and UK imaging guidelines.

Awareness of head and neck mucosal melanoma (HNMM) is important, as incorrect work-up can impact on the investigation and management of this rare and aggressive cancer. Following on from the 2020 HNMM UK guidelines, we set out the imaging recommendations and their rationale. To illustrate the key imaging characteristics, we also include a case series from our centre. All HNMM cases managed at our institution from January 2016 to January 2021 were identified, and the available imaging for each patient was reviewed. For each patient, the age, gender and location of primary tumour was recorded together with key staging and diagnostic imaging parameters. A total of 14 patients were identified. The median age was 65years with a female to male ratio of 1.33:1. Primary tumours were sinonasal in location in 93% of cases, with 7% of patients having metastatic neck nodes at presentation and 21% of cases having distant metastatic disease at presentation. This data set is in general concordance with other published series regarding the sinonasal origin of the vast majority of HNMM tumours along with the proportion of patients with metastatic neck nodes and distant metastases at presentation. We recommend dual-modality imaging with computed tomography (CT) and magnetic resonance imaging (MRI) of primary tumours whenever possible. In the systematic staging of HNMM, positron emission tomography (PET)-CT should be strongly considered, together with MRI of the brain. Pre-biopsy imaging of HNMM tumours is advisable whenever possible.

The Impact of Facility Type and Volume on Outcomes in Head and Neck Mucosal Melanoma

To evaluate differences in treatment outcomes for head and neck mucosal melanoma (HNMM) patients seen at academic versus nonacademic centers and high versus low volume facilities. Retrospective cohort study. National Cancer Database. Differences in treatment course and overall survival (OS) by facility type and volume were assessed for 2772 HNMM cases reported by the 2004 to 2017 National Cancer Database. A subgroup analysis was performed with a smaller cohort containing staging data. The analysis employed Kaplan-Meier and Cox proportional hazards models. A higher proportion of patients treated at academic centers within the HNMM cohort waited longer for surgery after diagnosis (p < .001), had negative surgical margins (p < .001), and were readmitted to the hospital within 30 days of surgery (p = .001); these relationships remained significant when controlling for cancer stage. Kaplan-Meier analysis demonstrated higher 5-year OS for patients treated at academic versus nonacademic facilities within the main cohort (32.5% ± 1.3% vs 27.3% ± 1.5%; p = .006) and within the stage-controlled subgroup (34.8% ± 2.1% vs 27.2% ± 2.6%; p = .003). Treatment at high volume versus low volume facilities was associated with improved 5-year OS for main cohort patients (33.5% ± 1.7% vs 28.8% ± 1.2%; p = .016) but not for subgroup patients (35.3% ± 2.7% vs 30.1% ± 2.1%; p = .100). Upon multivariate analysis controlling for demographic and oncologic factors, there was no significant difference in OS by facility type (main cohort: odds ratio [OR] = 1.07, 95% confidence interval [CI] = 1.01-1.21; subgroup: OR = 1.13, 95% CI = 0.97-1.32). Neither facility type nor surgical volume predicts overall survival in HNMM.

880P Phase II trial of the cyclin dependent kinase 4/6 inhibitor SHR6390 in patients with advanced head and neck mucosal melanoma harboring CDK4 amplification

Mucosal melanoma (MM) is a rare but devastating subtype of melanoma with 5-year survival rates ranging from only 16% to 25%. Our previous studies have demonstrated robust anti-tumor effects of CDK 4/6 inhibitors in head and neck MM (HNMM) patients (pts) derived xenograft models with CDK4 amplification. We performed a phase II study to determine the efficiency and safety of SHR6390, a CDK4/6 inhibitor, in pts with HNMM harboring CDK4 amplification.

Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Head and Neck Mucosal Melanoma.

BackgroundAccurate forecasting of the risk of death is crucial for people living with head and neck mucosal melanoma (HNMM). We aimed to establish and validate an effective prognostic nomogram for HNMM.MethodsPatients with HNMM who underwent surgery between 2010 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database for model construction. After eliminating invalid and missing clinical information, 288 patients were ultimately identified and randomly divided into a training cohort (199 cases) and a validation cohort (54 cases). Univariate and multivariate Cox proportional hazards regression analyses were performed in the training cohort to identify prognostic variables. Independent influencing factors were used to build the model. Through internal verification (training cohort) and external verification (validation cohort), the concordance indexes (C-indexes) and calibration curves were used to evaluate the predictive value of the nomogram.ResultsFor the training cohort, five independent risk predictors, namely age, location, T stage, N stage, and surgery, were selected, and nomograms with estimated 1- and 3-year overall survival (OS) and cancer-specific survival (CSS) were established. The C-index showed that the predictive performance of the nomogram was better than that of the TNM staging system and was internally verified (through the training queue: OS: 0.764 vs 0.683, CSS: 0.783 vs 0.705) and externally verified (through the verification queue: OS: 0.808 vs 0.644, CSS: 0.823 vs 0.648). The calibration curves also showed good agreement between the prediction based on the nomogram and the observed survival rate.ConclusionThe nomogram prediction model can more accurately predict the prognosis of HNMM patients than the traditional TNM staging system and may be beneficial for guiding clinical treatment.

Adjuvant Therapy and Prognosticators of Survival in Head and Neck Mucosal Melanoma.

To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). Retrospective database study. The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P= .036). SI (HR 0.425; P= .024) and SRI (HR 0.594; P= .045) were associated with superior OS than SR. Older age (HR 1.607; P< .001), female sex (HR 0.757; P= .006), paranasal sinus localization (HR 1.648; P< .001), T4 classification (HR 1.443; P< .001), N1 classification (HR 2.310; P< .001), M1 classification (HR 3.357; P< .001), and positive surgical margins (HR 1.454; P< .001) were survival prognosticators. Adjuvant radiotherapy use was negatively correlated with older age, oral cavity localization, and M0 or T3 tumors (all P< .05). Adjuvant immunotherapy use was positively correlated with younger age and M1 tumors (all P< .05). Although SR did not confer survival benefits in HNMM patients, SI and SRI yielded greater OS than surgery alone. SRI was associated with superior survival outcomes than SR. Certain demographic and clinical factors were associated with increased mortality risk. Patient age and certain tumor characteristics were predictors of adjuvant radiotherapy or immunotherapy use. 4 Laryngoscope, 132:584-592, 2022.

Adjuvant radiotherapy plus systemic chemotherapy in resected head and neck mucosal melanoma.

e18042 Background: The median over survival (OS) of resected head and neck mucosal melanoma (HNMM) is 49.0 months. About 65% of patients experience local recurrence or distant metastasis after surgery. Therefore, adjuvant therapy is critical to improve the poor prognosis. Methods: Data regarding HNMMs with radical surgery (stage III-IVa, AJCC HNMM 8th version) between September 1, 2006 and February 28, 2020 at Peking University Cancer Hospital was collected retrospectively. Postoperative radiotherapy was usually prescribed as GTV 60-70Gy/CTV 60Gy/30f. Patients were divided into four groups by the adjuvant regimens: radiotherapy+chemotherapy (RC), chemotherapy (C), radiotherapy (R) and observation (O). Results: In total, 368 patients were enrolled, including 104 RC,114 C, 53 R, 97 O, respectively. After median follow-up of 63.9 mo (range: 0.9-146.7), the median local relapse-free survival (LRFS) was 10.1 mo (95%CI: 6.7-13.6) in the O group, as compared with 65.9 mo (95%CI: 31.7-100.1, P＜0.001) in the R group, 75.6 mo (95%CI: 50.1-101.0, P＜0.001) in the C group, and 84.6 mo (95%CI: 48.5-120.8, P＜0.001) in the RC group. The median distant metastasis-free survival (DMFS) was 13.7 mo (95%CI: 8.0-19.5) in the O group, 15.3 mo (95%CI: 8.7-21.9, P = 0.898) in the R group, as compared with 25.7 mo (95%CI: 14.6-36.8, P = 0.001) in the C group, 49.3 mo (95%CI: 32.6-66.0, P＜0.001) in the RC group. Estimated OS was 36.4 mo (95%CI: 24.0-48.8) in the O group, as compared with 30.8 mo (95%CI: 23.0-38.6, P = 0.733) in the R group, 40.8 mo (95%CI: 34.8-46.8, P = 0.289) in the C group, 58.2 mp (95%CI: 36.4-79.9, P = 0.002) in the RC group. Primary location, age, gender, UICC staging and adjuvant regimens were included for multivariate Cox analysis. With regard to OS, UICC stage and RC were the prognostic factors. With regard to DMFS, UICC stage, RC and C were the prognostic factors. With regard to LRFS, UICC stage, RC, R, C were the prognostic factors. Conclusions: It is the largest study on the role of adjuvant radiotherapy and chemotherapy on HNMM till now. The results demonstrate that postoperative radiotherapy improves LRFS but has no impact on DMFS, while adjuvant radiotherapy plus chemotherapy prolongs OS. It further validates the clinical practice of UICC stage of HNMM, which might shed lights on the study of the whole mucosal melanoma.

Clinical characterization and treatment of head and neck mucosal melanoma: a Chilean experience

Head and neck mucosal melanoma (HNMM) is a rare disease with a poor prognosis. The aim of this research was to analyze clinical characteristics and prognostic factors in a Latin American cohort. A retrospective chart review of patients with HNMM treated between 2008 and 2019 was conducted. Demographic characteristics, tumor characteristics, surgical treatment, adjuvant therapy, and oncologic outcomes were recorded. Twenty HNMMs were identified; 60% were in men. The most frequent primary location was the nasal cavity (10; 50%). Regional disease was uncommon and limited to the oral cavity. The median overall survival was 29 months; the 3- and 5-year overall survival rates were 37.2% and 26.6%, respectively. Univariate analysis revealed that predictors of a worse overall survival were paranasal location (hazard ratio [HR], 4.61; 95% confidence interval [CI], 1.61-18.40; P=.030), positive lymph nodes (HR, 6.00; 95% CI, 1.30-27.7; P=.022), positive margins (HR, 4.32; 95% CI, 1.08-17.2; P=.039), bone invasion (HR, 3.27;95% CI, 1.05-10.1; P=.041), and lymphovascular invasion (HR, 3.82; CI, 1.03-14.2; P=.045). Three-year recurrence-free survival was 17.3%, and most of the recurrences were with distant disease. HNMM is an infrequent disease with an aggressive behavior. Survival outcomes are related to location of the primary disease, regional spread, lymphovascular invasion, and bone invasion.

CDK4 and TERT amplification in head and neck mucosal melanoma.

Recent high-throughput sequencing studies have revealed frequent CDK4 and TERT amplification in mucosal melanoma, suggesting that they are potential therapeutic targets. In this study, we investigated the statuses of CDK4 and TERT in head and neck mucosal melanoma (HNMM) with the aim of providing preclinical data to support future clinical trials. In total, 29 HNMM samples were collected, including 16 oral mucosal melanoma (OMM) samples and 13 nasal cavity/sinuses melanoma (SNMM) samples. Fluorescence in situ hybridization was used to analyze CDK4 and TERT amplification, and immunohistochemistry was used to analyze CDK4 and TERT protein expression patterns. CDK4 expression was knocked down in the ME cells (an OMM cell line), and changes in cell cycle were analyzed. Cell viability assays were performed to determine the sensitivity of ME to abemaciclib (a CDK4 inhibitor) combined with dacarbazine (an anti-melanoma chemotherapy drug). We detected five samples exhibited CDK4 amplifications and nine samples exhibited TERT amplifications in our HNMM series, and found that CDK4 amplification tended to occur in combination with TERT amplification. Amplifications of CDK4 and TERT were more common in OMM than in SNMM. Amplifications of CDK4 and TERT were associated with greater CDK4 and TERT protein expression levels. CDK4 knockdown led to delayed G1/S phase transition in ME cells. Furthermore, ME cells were sensitive to abemaciclib (IC50 =5.23nM). Abemaciclib and dacarbazine synergistically inhibited ME cells' viability. We confirmed high frequencies of CDK4 and TERT amplification in OMM. Combined therapy with a CDK4/6 inhibitor and anti-melanoma chemotherapeutic agents will be a reasonable strategy for future clinical trials concerning unresectable or metastatic OMM.

Prognostic value and therapeutic implications of nodal involvement in head and neck mucosal melanoma.

The prognostic significance of nodal involvement is not well established in head and neck mucosal melanoma (HNMM). A retrospective, monocentric study was performed on 96 patients with HNMM treated between 2000 and 2017. At diagnosis, seventeen patients (17.8%) were cN1, with a higher risk for HNMM arising from the oral cavity (p = 0.01). cN status had no prognostic value in patients with nonmetastatic resectable HNMM. No occult nodal metastasis was observed in the cN0 patients after a nodal dissection (ND). The nodal recurrence rate was similar in the cN1 and the cN0 patients. No isolated nodal recurrences were noted. Among the patients who underwent a ND, no benefit of this procedure was noted. cN1 status is not a prognostic factor in patients with resectable HNMM. Elective ND should not be systematically performed in cN0 HNMM.

Prognostic values of treatment modalities on head and neck mucosal melanomas in elderly patients: a population-based analysis.

BackgroundHead and neck mucosal melanoma (HNMM) is defined as a rare malignant tumor derived from melanocytes. There is no consensus regarding the treatment protocol for HNMM in elderly patients.MethodsThe National Cancer Institute’s Surveillance, Epidemiology, and End Results database was used to identify elderly patients diagnosed with HNMM from 1975 to 2016. The chi-squared test was used to compare patient characteristics. The reverse Kaplan-Meier method was used to estimate the median follow-up time. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival (OS) and disease-specific survival (DSS) of the groups. Cox regression analysis was used to evaluate the risk factors for OS and DSS of HNMM.ResultsOur retrospective study included 828 elderly patients with HNMM, and the 5-year OS and DSS rates were 22.4% and 27.4%, respectively. After adjusting for other variables in multivariate analysis, patients undergoing radiotherapy alone had worse OS [hazard ratio (HR) =1.449, 95% confidence interval (CI): 1.010–1.742, P=0.006] and DSS (HR =1.656, 95% CI: 1.257–2.181, P<0.001) than those undergoing surgery alone. No significant difference in OS (HR =0.892, 95% CI: 0.753–1.056, P=0.183) or DSS (HR =0.917, 95% CI: 0.764–1.101, P=0.354) was observed for patients undergoing surgery with or without radiotherapy. Our analysis of the subgroup of patients with complete clinical staging information demonstrated that the effects of surgery alone on OS (HR =0.734, 95% CI: 0.562–0.958, P=0.023) were inferior to those of surgery with radiotherapy, but no significant difference was noted compared with radiotherapy alone.ConclusionsThe survival of elderly patients with HNMM is increased with the combination of surgery and radiotherapy compared with surgery alone and radiotherapy alone. In addition, the population-based analysis demonstrated that combination therapy exhibited an obviously increased usage rate from 1975 to 2016, representing a mainstream treatment modality.

Mucosal Melanoma of the Head and Neck: A Retrospective Review and Current Opinion.

Introduction: Head and Neck Mucosal Melanoma (HNMM) is an uncommon malignancy that arises in decreasing order in the nasal cavity, the paranasal sinuses, and the oral cavity. Although radical surgery followed by eventual radiotherapy is acknowledged as the mainstay treatment, patients with advanced stages or multi-focal tumors benefit from new systemic therapies. We wish to share our experience with these treatments and review the current literature.Materials and Methods: We present a case review of every patient treated in our center for an HNMM over the past 10 years, including every patient treated in our center for an HNMM over the past 10 years. We analyzed clinical characteristics, treatment modalities, and outcomes.Results: We included eight patients aged from 62 to 85 years old. We found six MM in the nasal cavity, one in the sphenoidal sinus, and one in the piriform sinus. Six patients underwent endoscopic surgery with negative margins, six underwent radiotherapy with variable modalities. Immunotherapy or targeted therapy was given in cases extensive tumors without the possibility of a surgical treatment or in two patient as an adjuvant treatment after R0 surgery. The three-year overall survival was 50%, and three patients (37.5%) are in remission.Conclusions: HNMM is associated with poor oncologic outcomes regarding the concerned patients of our review, as reported in the literature. New treatments such as immunotherapies or targeted therapies have not significantly changed the prognosis, but they may offer new interesting perspectives.Our small series of cases seems to confirm that surgical resection with negative margins improves overall survival.

The effectiveness of radiotherapy in the treatment of head and neck mucosal melanoma: Systematic review and meta-analysis.

Mucosal melanoma (MM) is a rare condition with a poor prognosis. Surgery is the corner stone of treatment, however, radiotherapy has been commonly employed as a treatment strategy and recent studies suggesting that survival outcomes may be improving are emerging. A systematic review and meta-analysis comparing risk ratios of radiotherapy and surgery and radiotherapy (SRT) with surgery for 5-year overall survival, local recurrence and distant metastasis in head and neck mucosal melanoma (HNMM). SRT has a lower risk of death compared to surgery [RR 0.93 [95% CI = 0.87, 0.98] (P = .01)] and a reduced risk of local recurrence [RR 0.63 [95% CI = 0.48, 0.82] (P = .005)]. SRT has no effect on distant metastasis. Radiotherapy has worse survival when compared to surgery [RR 1.2 [95% CI = 1.03, 1.33] (P = .0006)]. SRT confers a moderate survival advantage in HNMM compared to surgery. This is most likely secondary to reduced local recurrence.

Analysis of prognostic factors for survival in patients with head and neck mucosal melanoma

Objective:To analysis the clinical and histopathological features, and the effect of surgical treatment and adjuvant therapy for the survival in patients of head and neck mucosal melanoma（HNMM）. Method:A retrospective analysis was conducted on the clinical data of 46 patients with HNMM, and the factors related to survival were analyzed. Kaplan-Meier analysis was used for survival analysis. Log-rank test was used for univariate analysis, and COX proportional hazard model was used for multivariate analysis. Result:The 3 and 5 year cumulative survival rates of 46 patients with HNMM were 47.5% and 34.1%, respectively, and the median survival time was 36 months. Univariate analysis revealed that the factors affecting survival rates in patients with HNMM included tumor staging, surgical margins, postoperative targeted therapy, distant metastasis and local recurrence（P<0.05）. Multiple factor COX regression analysis showed that distant metastasis, tumor staging, surgical margins were independent risk factors for survival rates in patients with HNMM, and postoperative targeted therapy was the protective factor. Conclusion:HNMM is of high malignancy and low survival rate. Early diagnosis and complete surgical resection are the primary methods to improve the survival, and postoperative targeted therapy may be an intervention to improve the survival.

Efficacy and safety of primary surgery with postoperative radiotherapy in head and neck mucosal melanoma: a single-arm Phase II study.

BackgroundThere still remains no well-established treatment strategy for head and neck mucosal melanoma (HNMM). We aim to evaluate the effectiveness and safety of primary surgery with postoperative radiotherapy for this disease.Patients and methodsA single-arm, Phase II clinical trial was conducted at Sun Yat-Sen University Cancer Center. Patients with nonmetastatic, histologically proven HNMM were prospectively enrolled. Patients received primary surgery followed by intensity-modulated radiotherapy with an equivalent dose at 2 Gy per fraction of 65–70 Gy to CTV1 (high-risk regions including tumor bed) and 50–55 Gy to CTV2 (low-risk regions). Additional use of adjuvant chemotherapy (AC) depended on consultation from a multidisciplinary team. This trial is registered with ClinicalTrials.gov, number NCT03138642.ResultsA total of 33 patients were enrolled and analyzed between July 2010 and November 2016. There were 18 (54.5%) patients with T3 disease and 15 (45.5%) patients with T4a disease. The median age at diagnosis was 58 years (range 27–83 years), and 61% of the cohort were males. The overall median follow-up duration was 25.3 months (range 5.3–67.1 months). The 3-year overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were 44.4, 91.7, 78.1, and 41.7%, respectively. Patients with T4a disease showed significantly inferior OS (P=0.049) and DMFS (P=0.040) than those with T3 disease. Prophylactic neck radiation (PNR) was nearly associated with superior RRFS (P=0.078). However, there was no significant difference in OS, LRFS, RRFS, and DMFS for patients treated with or without AC (P>0.05 for all). Toxicities were generally mild to moderate.ConclusionPrimary surgery with postoperative radiotherapy yielded excellent local control and acceptable toxicity profile for HNMM. Nevertheless, high rates of distant metastases resulted in limited survival.

Mucosal melanoma of the cranio-facial region: Surgical challenges and therapeutic options

ObjectiveAlthough current therapeutic options for cutaneous melanoma (CM) are constantly improving survival, mucosal melanoma (MM) remains a rare tumor disease with a poor clinical outcome. While radical surgery is the gold standard, clear margin resections in the head and neck area are particularly critical due to high density of vulnerable structures. Adjuvant therapeutic options increases local control and data on the effect of systemic agents is sparse. The aim of this study was to elucidate surgical challenges in the craniofacial area and to evaluate the effect of local and systemic therapy in Head and Neck Mucosal Melanoma (HNMM). MethodsIn total, 21 patients with nasal mucosal malignant melanoma were included in this study over the course of 20 years in two German tertiary referral centers. Patient characteristics and conducted therapy as well as clinical outcomes were analyzed retrospectively. ResultsBy performing survival analysis for multimodal therapies, we observed a superiority effect of interferon therapy compared to surgery with radiation and surgery alone in the first therapeutic approach. However, patients treated with surgery alone in a recurrent setting showed the best outcome. ConclusionBoth, Interferon and radiation as adjuvant therapies, demonstrated survival benefits in initial treatment compared to surgery alone. Analysis after recurrence, however, revealed salvage surgery as a reliable and powerful tool to prolong post-recurrence survival without exposing palliative patients to the risk of severe adverse events from systemic therapies.

KIT, NRAS and BRAF mutations in head and neck (upper aerodigestive tract) mucosal melanoma (a study of 21 cases)

Objective . Determination of mutation rates in KIT, NRAS and BRAF genes in 21 samples of mucosal melanoma of the upper aerodigеstive tract. Background. Head and neck mucosal melanomas (or upper aerodigestive tract mucosal melanomas) are rare and aggressive tumors of melanocytic origin. Head and neck mucosal melanoma (HNMM) comprises over 50 % of all mucosal melanomas. The aim was to determine the KIT, NRAS and BRAF mutation frequencies in 21 series of primary HNMM. Methods . Microdissected tumour cells were used from 21 formalin-fixed paraffin-embedded tumours. The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing. Results. Overall, 19 % (4 out of 21) of HNMMs harboured KIT, NRAS or BRAF mutations. Mutations in these oncogenes occurred in a mutuаlly exclusive manner. Both NRAS and BRAF mutations were identified at a similar frequency of 4,75 % each (1 and 1 out of 21), whereas KIT mutations were detected in 9,5 % (2 out of 21) of the HNMMs. KIT mutations were located in exon 11. Conclusion. Our findings shоw that NRAS and BRAF mutations, which are aсcessible for present targeted thеrapies, are only rarеly present in HNMMs, whereas KIT mutations seem to be relatively more frequent.