HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

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Malignant mucosal melanoma of the paranasal sinuses: Two case presentations

Primary mucosal melanoma of the paranasal sinuses is a rare tumor of the head and neck which can be a devastating disease. Cancers arising in the sinonasal cavity are extremely rare, with a poor survival rate. There is inherent difficulty in diagnosing these lesions due to their complex anatomic locations and symptoms which are often confused with more common benign processes. The primary treatment of this rare disease process is resection, except in advanced stages where surgical resection is not an option. Diagnostic accuracy in consideration of size, location, and presence of metastatic disease of these malignant tumors tailors individual patients to different management in order to achieve the longest possible survival.     

Patterns of failure after combined-modality approaches incorporating radiotherapy for sinonasal undifferentiated carcinoma of the head and neck

PURPOSE: To report the clinical outcome of patients treated with combined-modality approaches for sinonasal undifferentiated carcinoma (SNUC) of the head and neck. METHODS AND MATERIALS: The records of 21 patients with SNUC treated with curative intent at the University of California, San Francisco between 1990 and 2004 were analyzed. Patient age ranged from 33 to 71 years (median, 47 years). Primary tumor sites included the nasal cavity (11 patients), maxillary sinus (5 patients), and ethmoid sinus (5 patients). All patients had T3 (4 patients) or T4 (17 patients) tumors. Local-regional treatment included surgery followed by postoperative radiotherapy (PORT) with or without adjuvant chemotherapy for 17 patients; neoadjuvant chemoradiotherapy followed by surgery for 2 patients; and definitive chemoradiotherapy for 2 patients. Median follow-up among surviving patients was 58 months (range, 12-70 months). RESULTS: The 2- and 5-year estimates of local control were 60% and 56%, respectively. There was no difference in local control according to initial treatment approach, but among the 19 patients who underwent surgery the 5-year local control rate was 74% for those with gross tumor resection, compared with 24% for those with subtotal tumor resection (p = 0.001). The 5-year rates of overall and distant metastasis-free survival were 43% and 64%, respectively. Late complications included cataracts (2 patients), lacrimal stenosis (1 patient), and sino-cutaneous fistula (1 patient). CONCLUSION: The suboptimal outcomes suggest a need for more effective therapies. Gross total resection should be the goal of all treatments whenever possible.     

Current management of mucosal melanoma of the head and neck

While mucosal-based melanomas of the head and neck region are uncommon lesions, when they do arise they usually follow an inexorably aggressive course. Experience with these tumors is, necessarily, limited; as such, well-worked out treatment protocols for the treatment of such lesions are in short supply. It appears as though mucosal melanomas (MuMs) develop more frequently in the nasal cavity and paranasal sinus region, and less often in the oral cavity. It seems that the incidence of nodal metastasis is significantly lower for sinonasal MuMs than it is for MuMs of the oral cavity; this observation may influence decisions about performing neck dissection as a function of location of the primary MuM. At present, surgical excision remains the mainstay of treatment; however, anatomical complexities within the region can hamper attempts at complete excision. Radiotherapy has not traditionally been relied on for routine treatment of MuM, although some recent reports have challenged this view. Chemotherapy is, at present, employed principally in the treatment of disseminated disease and for palliation. As a diagnostic matter, MuM belongs to the class of tumors that, on light microscopy, may with some regularity be confused with other malignancies (including sarcomas, plasmacytomas, and carcinomas); as a consequence, this is a diagnosis which is often best confirmed by way of ancillary testing via immunohistochemical studies. A better grasp of the best means of treating MuM will likely come only when large referral centers are able to pool their experiences with these uncommon yet virulent malignancies.     

Malignant mucosal melanoma treated with carbon ion radiotherapy with concurrent chemotherapy: Prognostic value of pretreatment apparent diffusion coefficient (ADC)

Background and purpose

To evaluate the potential of apparent diffusion coefficient (ADC) value before carbon ion radiotherapy (C-ion RT) for malignant mucosal melanoma (MMM) to predict prognosis.

Materials and methods

We recruited 37 patients with MMM in the head and neck treated by C-ion RT with concomitant chemotherapy. Univariate and multivariate analyses of minimum ADC, mean ADC, tumor volume, age, PS, and gender were performed to identify prognostic factors.

Results

The 3-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 81.1%, 37.6% and 65.3%, respectively, with a median follow-up period of 19.0 months. In univariate analyses, lower minimum ADC (?0.6380 × 10⁻³ mm²/s) and lower mean ADC (?1.1523 × 10⁻³ mm²/s) were unfavorable prognostic factors for distant metastasis (p = 0.029 and p = 0.014, respectively), and lower minimum ADC was an unfavorable prognostic factor for overall survival (p = 0.019). However, there was no significant prognostic factor of local control including ADC value. In multivariate analyses, only minimum ADC was selected as a prognostic factor of distant metastasis-free survival and overall survival (p = 0.015 and p = 0.006, respectively).

Conclusion

Minimum ADC can be a prognostic factor of MMM in the head and neck after C-ion RT.     

Malignant mucosal melanoma of the head and neck — a review

Mucosal melanomas comprise about 1% of all malignant melanomas and exhibit far more aggressive behaviour than that of skin melanomas: they are more inclined to metastatize into regional and distant sites or recur locally, regionally or in distant locations, resulting in a high rate of cause-specific death. Mucosal melanomas in the head and neck region account for half of all mucosal melanomas, occurring mainly in the upper respiratory tract, oral cavity and pharynx. They appear with equal gender distribution and with a peak incidence in the age range 60-80 years. In consequence of their hidden location, they are usually diagnosed in a locoregionally advanced clinical stage, with a rate of 5-48% of regional and 4-14% of distant dissemination. The typical therapeutic approach is surgery, postoperative irradiation and systemic therapy. Local control with either surgery or radiotherapy is frequently (60- 70%) achieved, but the rates of local, regional and distant recurrences are high (50-90%, 20-60% and 30-70%, respectively). The reported 5-year actual survival rates are poor (17-48%), which is attributed mainly to a haematogenous dissemination. These characteristics demonstrate that identification of the precursor lesions and more effective local and systemic approaches are needed to improve the therapeutic results.     

放射性黏膜损伤的营养治疗策略

黏膜损伤是头颈肿瘤放疗中最常见的并发症,主要表现为口腔疼痛、吞咽困难、进食减少以及继发性感染,严重时可导致治疗中断,影响治疗疗效和患者生活质量。伤口修复依赖营养,不合理的营养方案影响修复进程。因此,促进黏膜损伤的快速修复,合理的营养策略十分重要。本文基于目前放射性黏膜损伤和营养素对黏膜修复作用及其机制的研究,针对放射性黏膜损伤的流行病学、病理生理机制、临床表现和营养策略进行综述,为临床提供参考。     

头颈部原发性黏膜恶性黑色素瘤患者PD－L 1表达及其临床相关因素分析

目的：探讨头颈部原发性黏膜恶性黑色素瘤患者程序性细胞死亡配体1（PD－L1）表达及其临床意义。方法：研究采用免疫组化检测45例头颈部原发性黏膜恶性黑色素瘤样本PD－L1表达,分析其表达与患者临床病理学特征及疾病预后的关系。结果：所有患者均接受手术切除治疗联合干扰素治疗。随访患者5年生存率为44．4％（20／45）,平均生存期为51个月,无复发生存期为23个月。免疫组化染色证实57．8％（26／45）肿瘤样本为 PD －L1高表达,显著多与临近非肿瘤组织（P＝0．0037）。PD－L1表达与患者年龄（P＝0．09）、性别（P＝0．16）、肿瘤分布（P＝0．08）无关,而PD－L1阳性患者的无复发生存期显著短于阴性患者（P＝0．027）。多变量分析证实PD－L1高表达是头颈部原发性黏膜恶性黑色素瘤患者预后不良独立标志物。结论：PD－L1高表达与头颈部原发性黏膜恶性黑色素瘤进展和预后不良密切相关,可以作为该疾病的预后标志物。     

白细胞介素-11预防和治疗头颈部肿瘤放疗导致口腔黏膜反应的疗效观察

目的 探讨预防和治疗头颈部肿瘤放疗性口腔黏膜反应的有效方法.方法 对2008年3月至2010年3月间50例头颈部肿瘤放疗患者随机分组对照观察.在放射治疗期间,观察组给予白细胞介素-11(IL-11)局部雾化吸入,对照组未给予IL-11.结果 观察组患者对IL-11耐受性良好,并在降低口腔黏膜反应程度、减轻疼痛和增进患者食欲等方面效果显著(P<0.05).患者的疼痛时间由对照组的4.5 d±1.3 d减为观察组的2.3 d±1.0 d,愈合时间由对照组的7.3 d±1.5 d减为观察组的4.1 d±1.7 d,差异有统计学意义(P<0.05).结论 IL-11对预防和治疗头颈部肿瘤放疗性口腔黏膜反应有显著疗效,可减轻放疗性口腔黏膜反应给患者带来的痛苦,提高了生活质量.     

Patterns of failure in patients with cutaneous head and neck melanoma

IntroductionThe incidence of head and neck melanoma is increasing. Various factors influence prognosis.ObjectiveWe sought to investigate the subgroup of patients with head and neck melanoma who fail primary treatment and to define the patterns of failure.MethodsThe database of a tertiary medical center was reviewed for patients diagnosed and surgically treated for cutaneous head and neck melanoma in 1995–2014. Regional disease failure was defined as disease confirmed in positive SLNB at first assessment or at recurrence.ResultsThe cohort included 141 patients followed for a median duration of 6.8 years (range 1–20 years). Median tumor thickness was 2.1 mm (range 0.5–12 mm). Ulceration was documented in 38 patients (26.9%). Sentinel lymph node biopsy (SLNB) was positive in 18 patients (12.8%). Total disease failure rate was 32.6% with similar rates of regional (n = 26, 18.4%) and distal (n = 22, 15.6%) failure. Most patients (86.3%) with systemic recurrence had a negative SNLB as did 6/26 patients (23%) with regional failure. Forty-three patients (30.4%) died during follow-up, half of them (23 patients, 16.3%) of melanoma. On multivariate analysis, Breslow thickness was the only significant predictor of outcome.ConclusionsThe pattern of treatment failure in patients with head and neck melanoma relate predominantly to Breslow thickness. The high false-negative rate of SNLB and the relatively high rate of systemic failures in patients with negative SNLB indicate a low predictive value of this procedure. Efforts to detect systemic disease during follow-up need to be intensified.     

A cohort analysis of surgically treated primary head and neck lentigo maligna (melanoma): Prognostic value of melanoma subtype and new insights in the clinical value of guideline adherence

BackgroundKnowledge about lentigo maligna (melanoma) (LM/LMM) and its associated prognostic clinicopathological characteristics are limited compared to that of non-LM/LMM subtypes. The current study aimed to determine the clinical relevance of the LM/LMM subtype and its influence on recurrence and survival outcomes.MethodsAll consecutive cases of primary cutaneous head and neck LM/LMM treated by wide local excision over a ten-year period were retrospectively reviewed and compared to non-LM/LMM. Clinical outcome and prognostic factors were assessed by cumulative incidence and competing risk analyses.ResultsA total of 345 patients were identified. Specific clinicopathological characteristics such as lower median Breslow thickness (1.6 mm versus 2.1 mm; P = 0.013), association with diagnostic sampling errors (17.3% versus 5.2%; P = 0.01), and increased risk of local recurrences due to incomplete resection (18.7% versus 2.3%; P < 0.001), were significantly associated with LM/LMM. Guideline adherence was similar between the two study groups. The positive nodal status at baseline for LMM was low compared to non-LM/LMM (4.2% vs 17.9%; P = 0.037). The LMM subtype, facial localization, and reduced surgical margins (i.e., guideline non-adherence) were not shown to be independent prognostic factors for disease-free, melanoma-specific, or overall survival after correction for competing risks such as patient age and Breslow thickness.ConclusionsThe LMM subtype was not shown to be prognostically different from non-LM/LMM when corrected for other variables of influence such as patient age and Breslow thickness. Reduced resection margins did not seem to affect disease-free, and melanoma-specific survival and warrant LM/LMM-specific guidelines. Further research is needed to evaluate the value of SLNB in LMM patients.     

Management of Clitoral Melanoma Presenting as an Exophytic Clitoral Mass: A Case Report and Review of the Literature

Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract.