Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases. Herein, we summarized the relevant evidence and provided an algorithm for decision-making in MCC management based on the latest 2021 National Comprehensive Cancer Network guidelines. Additionally, we report current active MCC clinical trials in the United States. The initial management of MCC is dependent upon the pathology of the primary tumor and presence of metastatic disease. Patients with no clinical evidence of regional lymph node involvement generally require sentinel node biopsy (SLNB) while clinically node-positive patients should undergo fine needle aspiration (FNA) or core biopsy and full imaging workup. If SLNB or FNA/core biopsy are positive, a multidisciplinary team should be assembled to discuss if additional node dissection or adjuvant therapy is necessary. Wide local excision is optimal for primary tumor management and SLNB remains the preferred staging and predictive tool in MCC. The management of MCC has progressively improved in the last decade, particularly due to the establishment of immunotherapy as a new treatment option in advanced MCC. Ongoing trials and prospective studies are needed to further establish the best practices for MCC management.

Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st-3rd, 2022-Naples, Italy).

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and acquire resistance to immunotherapy and molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been shown to improve prognosis compared to monotherapy. The number of new combinations treatment under development for melanoma provides options for the number of patients to achieve a therapeutic benefit. Many diagnostic and prognostic assays have begun to show clinical applicability providing additional tools to optimize and individualize treatments. However, the question on the optimal algorithm of first- and later-line therapies and the search for biomarkers to guide these decisions are still under investigation. This year, the Melanoma Bridge Congress (Dec 1st-3rd, 2022, Naples, Italy) addressed the latest advances in melanoma research, focusing on themes of paramount importance for melanoma prevention, diagnosis and treatment. This included sessions dedicated to systems biology on immunotherapy, immunogenicity and gene expression profiling, biomarkers, and combination treatment strategies.

Prophylactic Lymphaticovenous Anastomosis Performed with Lymphadenectomy is Oncologically Safe for Melanoma.

BACKGROUND: A major concern of lymphaticovenous anastomosis (LVA), which has not been studied, is increased risk of metastasis. Melanoma patients with macrometastatic lymph node disease represent a high-risk group for recurrence and metastasis. On the basis of a literature review, this present study is the first to evaluate the impact of prophylactic LVA on cancer survival and recurrence. METHODS: This was a comparison study of patients with cutaneous melanoma who underwent therapeutic lymphadenectomy alone (comparison group) or combined with prophylactic LVA (LVA group) between 2014 and 2020. A single surgeon performed all cancer resections, therapeutic lymphadenectomies, and LVA. Exclusion criteria included non-melanoma skin cancers, stage IV cancers before lymphadenectomy, microscopic lymphatic disease (i.e., positive sentinel node biopsy was the sole indication for lymph node dissection), or follow-up time less than 12 months unless the patient died earlier owing to melanoma-related complications. RESULTS: This study included 23 patients in the LVA group and 22 consecutive patients in the comparison group. The two groups were similar in age, sex, and cancer stages. The comparison group had longer follow-up times (median 67.62 versus 29.73 months in the LVA group; p < 0.01). Average size of largest metastatic lymph node was 45.91 ± 35.03 mm and 44.54 ± 23.32 mm in the LVA and comparison groups, respectively (p = 0.99). There were no differences in OS, DMFS, and RFS times after more than 2 years of follow-up since the index surgery. CONCLUSION: Prophylactic LVA performed for macrometastatic melanoma is not a strong risk factor for relapse and metastasis. LEVEL OF EVIDENCE: II Therapeutic.

Immune status does not independently influence cutaneous squamous cell carcinoma metastasis and death when stratified by tumor stage: A dual-center retrospective cohort analysis of primary N0 disease.

BACKGROUND: Although immunocompromised patients have a higher risk of developing cutaneous squamous cell carcinomas, it is unknown whether immune status is an independent risk factor for poor outcomes. OBJECTIVE: To compare cutaneous squamous cell carcinoma outcomes in immunocompromised and immunocompetent patients when controlling for T-stage. METHODS: We performed a retrospective cohort study at 2 tertiary care centers, examining 989 primary tumors from 814 immunocompromised patients (solid organ transplant: 259 [31.7%], chronic lymphocytic leukemia: 113 [13.9%]) and 6608 tumors from 4198 immunocompetent patients. Our primary outcome was the composite of disease-specific death or tumor metastasis ("poor outcomes"). RESULTS: Immunocompromised patients had 50% more high T-stage tumors (ie, Brigham and Women's Hospital stage T2b and T3), than immunocompetent patients (3.3% vs 4.9%, respectively; P < .001). Significant predictors of poor outcomes included tumor stage (sub hazards ratio [SHR], 14.8 for high T-stage tumors; 95% confidence interval [CI], 8.0-27.6; P < .001) and male sex (SHR, 2.3; 95% CI, 1.4-3.8; P = .002). Immune status was not a significant predictor (SHR, 1.04; 95% CI, 0.69-1.6; P = .85). LIMITATIONS: This study is retrospective. CONCLUSION: Although immunocompromised patients had 50% more high T-stage tumors than immunocompetent patients, immunocompromised patients had a similar chance of metastasis and disease-specific death when adjusting for T-stage in our cohort of primary tumors.

Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

BACKGROUND: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not. OBJECTIVE: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions. METHODS: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold. RESULTS: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death. LIMITATIONS: Multicenter, retrospective study. CONCLUSION: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.

BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors.

AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-ß receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-ß. In preclinical studies with an immunocompetent mouse model, AdAPT-001 eradicated directly treated 'cold' tumors as well as distant untreated tumors, and, from its induction of systemic CD8+ T cell-mediated antitumor immunity, protected the mice from rechallenge with tumor cells. AdAPT-001 also sensitized resistant tumors to checkpoint blockade. This manuscript describes the rationale and design of the first-in-human phase I, dose-escalation and dose-expansion study of AdAPT-001 alone and in combination with a checkpoint inhibitor in adults with treatment-refractory superficially accessible solid tumors.

The purpose of this study is to find out more about the experimental oncolytic virus called AdAPT-001 that has been designed to selectively eliminate cancer cells. The virus is also designed to make a particular protein called a TGF-ß trap, which neutralizes TGF-ß, an overproduced chemical in cancer cells that puts the immune system into a comatose state. This article discusses a clinical trial called BETA PRIME for patients with no other standard treatment options. The trial will explore different doses of AdAPT-001 both alone and in combination with an approved checkpoint inhibitor or another immunotherapy, which blocks the 'off' signal on immune cells, to determine the safest and best dose. Clinical Trial Registration: NCT04673942 (ClinicalTrials.gov).

Youngest Composite Full-Face Transplant: A Model for Vascularized Composite Allograft in Younger Populations.

BACKGROUND: The field of face transplantation continues to evolve, with more complex defects being addressed, and, at the same time, increased outcome expectations. Given our unique long-term experience in this field, we consented one of the youngest patients to undergo a full-face transplant. METHODS: An 18-year-old woman presented with complete destruction of her central face and craniofacial structures. She had coexisting major injuries, including pituitary gland, visual axis, and motor control. After extensive rehabilitation and reconstruction techniques, the patient underwent face transplant on May 4, 2017, at the age of 21 years. RESULTS: The total operative time for the recipient was 26 hours. There were no major perioperative complications. Since transplant, the patient has undergone 3 revision surgeries. She is near completely independent from a daily life activity standpoint. She has had 1 episode of rejection above grade II that was successfully treated with a short-term increased in immunosuppression. CONCLUSIONS: Contrary to data in solid organ transplantation where youth is associated with increased risk of rejection, our current algorithm in immunosuppression, combined with this patient's compliance, has led to only 1 rejection episode beyond grade II. This successful transplant can serve as a model for future vascularized composite transplants in younger populations.

Maxillary and Mandibular Healing After Facial Allotransplantation.

INTRODUCTION: Facial transplantation has emerged as a viable option in treating devastating facial injuries.Despite the high healing rate of Le Fort III and bilateral sagittal split osteotomies (BSSO) in nontransplant patients, few studies have reported assessment of maxillary and mandibular healing in face transplant patients compared with nontransplant patients. The aim of this study was to examine differences in bone healing in our patients. PATIENTS AND METHODS: A retrospective chart review was conducted of facial allotransplantation patients at the Cleveland Clinic from December 2008 to inception. Demographics such as age, date of birth, and sex were recorded. Additional variables included procedures, revisions, reoperations, medications, and bone stability and healing. Computed tomography (CT) images assessed the alignment of skeletal components, bony union quality, and stability of fixation. RESULTS: Three patients were included: 2 had Le Fort III segment transplantation, and 1 had transplantation of both a Le Fort III segment and mandibular BSSO. The Le Fort III segment in all patients exhibited mobility and fibrous union at the Le Fort III osteotomy on CT. In contrast, the BSSO healed uneventfully after transplantation and revision surgery, with bony union confirmed by both CT and histology of the fixation area between the donor and recipient mandible bilaterally. No patients with midfacial fibrous union required revision of the nonunion as they were clinically asymptomatic. CONCLUSION: Le Fort osteotomy demonstrates inferior healing in facial transplantation compared with the nontransplant population. In contrast, the successful healing in the mandible is likely owing to the high density of rich cancellous bone.

Successful Treatment of Life-Threatening COVID-19 Infection in a Face Transplant Recipient.

ABSTRACT: Recent literature suggests that severe COVID-19 is associated with an exaggerated immune response during viral infection, resulting in cytokine storm. Although elevated plasma interleukin 6 (IL-6) has been reported in severe COVID-19 infections, and treatment with anti-IL-6 (tocilizumab) has demonstrated promising outcomes both domestically and abroad, reports remain limited and therapeutic regimens vary considerably. Furthermore, research pertaining to transplant recipients, COVID-19 infection, and anti-IL-6 therapy remains underdeveloped. Herein, we report the successful treatment of the only reported facial vascularized composite allograft (VCA) recipient who contracted severe COVID-19 and the first reported VCA recipient with COVID-19 infection that received anti-IL-6 immunotherapy resulting in an excellent recovery despite his multiple preexisting and COVID-19-related comorbidities-adult respiratory distress syndrome, acute renal failure requiring hemodialysis, and concomitant sepsis due to extensive drug-resistant bacterial pneumonia upon presentation. To date, he has not demonstrated any anti-IL-6 drug-related adverse effects. This preliminary report also suggests that our immunosuppressed VCA patients can indeed demonstrate a robust cytokine response during COVID-19 infection and may also respond favorably to emerging anticytokine immune therapies. We hope that our experience proves helpful to other centers that might encounter critically ill VCA recipients in the ongoing COVID-19 pandemic and in the years to follow.

Molecular risk prediction in cutaneous melanoma: A meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients.

BACKGROUND: Multiple studies have reported on the accuracy of the prognostic 31-gene expression profile test for cutaneous melanoma. Consistency of the test results across studies has not been systematically evaluated. OBJECTIVE: To assess the robustness of the prognostic value of the 31-gene expression profile. METHODS: Raw data were obtained from studies identified from systematic review. A meta-analysis was performed to determine overall effect of the 31-gene expression profile. Clinical outcome metrics for the 31-gene expression profile were compared with American Joint Committee on Cancer staging. RESULTS: Three studies met inclusion criteria; data from a novel cohort of 211 patients were included (n = 1,479). Five-year recurrence-free and distant metastasis-free survival rates were 91.4% and 94.1% for Class 1A patients and 43.6% and 55.5% for Class 2B patients (P < .0001). Meta-analysis results showed that Class 2 was significantly associated with recurrence (hazard ratio 2.90; P < .0001) and distant metastasis (hazard ratio 2.75; P < .0001). The 31-gene expression profile identified American Joint Committee on Cancer stage I to III patient subsets with high likelihood for recurrence and distant metastasis. Sensitivity was 76% (95% confidence interval 71%-80%) and 76% (95% confidence interval 70%-82%) for each end point, respectively. When 31-gene expression profile and sentinel lymph node biopsy results were considered together, sensitivity and negative predictive value for distant metastasis-free survival were both improved. CONCLUSION: The 31-gene expression profile test consistently and accurately identifies melanoma patients at increased risk of metastasis, is independent of other clinicopathologic covariates, and augments current risk stratification by reclassifying patients for heightened surveillance who were previously designated as being at low risk.

Incidence and outcomes of cutaneous angiosarcoma: A SEER population-based study.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, malignant tumor of vascular mesenchymal origin accounting for less than 1% of all sarcomas. OBJECTIVE: To examine epidemiologic trends and outcomes in CAS. METHODS: In this retrospective, population-based study, patients with CAS were identified from the Surveillance Epidemiology and End Results database. Age, sex, and race-standardized incidence rates (IRs) were calculated. Survival was assessed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 811 patients with CAS, 43% had a prior primary cancer. CAS IR for patients without prior primary cancers dropped from 5.88 per 100,000 in 1973 to 1984 to 2.87 per 100,000 in 2005 to 2014. In those with prior primary cancers, IR rose from 0.03 per 100,000 in 1973 to 1984 to 2.25 per 100,000 in 2005 to 2014. On multivariate analysis, patients older than 70 years of age had a higher risk of death compared with those younger than 50 years (hazard ratio, 2.16; 95% confidence interval 1.33-3.57; P = .002), and distant disease was associated with increased risk of death compared with localized disease (hazard ratio, 1.50; 95% confidence interval, 1.11-2.03; P = .008). Receipt of surgery and/or radiation therapy was not associated with survival. LIMITATIONS: Potential selection and miscoding bias, retrospective nature. CONCLUSION: CAS rates are rising among those with other prior primary cancers. Survival is not affected by current therapeutic strategies, highlighting the need for additional treatment options.

Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria.

BACKGROUND: A substantial number of patients who relapse and die from cutaneous melanoma (CM) are categorized as being at low risk by traditional staging factors. The 31-gene expression profile (31-GEP) test independently stratifies metastatic risk of patients with CM as low (Class 1, with 1A indicating lowest risk) or high (Class 2,with 2B indicating highest risk). OBJECTIVE: To assess risk prediction by the 31-GEP test within 3 low-risk (according to the American Joint Committee on Cancer) populations of patients with CM: those who are sentinel lymph node (SLN) negative, those with stage I to IIA tumors, and those with thin (≤1 mm [T1]) tumors. METHODS: A total of 3 previous validation studies provided a nonoverlapping cohort of 690 patients with 31-GEP results, staging information, and survival outcomes. Kaplan-Meier and Cox regression analysis were performed. RESULTS: The results included the identification of 70% of SLN-negative patients who experienced metastasis as Class 2, the discovery of reduced recurrence-free survival for patients with thin tumors and Class 2B biology compared with that of those with Class 1A biology (P < .0001); and determination of the 31-GEP test as an independent predictor of risk compared with traditional staging factors in patients with stage I to IIA tumors. LIMITATIONS: Diagnoses spanned multiple versions of pathologic staging criteria. CONCLUSIONS: The 31-GEP test identifies high-risk patients who are likely to experience recurrence or die of melanoma within low-risk groups of subpopulations of patients with CM who have SLN-negative disease, stage I to IIA tumors, and thin tumors.

Predictors of sentinel lymph node positivity in thin melanoma using the National Cancer Database.

BACKGROUND: Sentinel lymph node biopsy (SLNB) specimens are often obtained from patients for further staging after these patients have undergone melanoma excision. Limited data regarding predictors of SLNB positivity in thin melanoma are available. OBJECTIVE: We sought to evaluate predictors of SLNB positivity in thin melanoma. METHODS: Patients with cutaneous melanoma with a Breslow thickness ≤1.00 mm who received a SLNB were identified from the National Cancer Database between 2004 and 2014 (n = 9186). Predictors of SLNB positivity were analyzed using logistic regression. RESULTS: In a multivariate analysis, patients <60 years of age (P < .001) and Breslow thickness >0.8 mm (P = .03) were at increased risk for positive sentinel lymph node (SLN). Moreover, on multivariate analysis, the presence of dermal mitoses increased the odds of SLN positivity by 95% (odds ratio [OR] 1.95 [95% confidence interval {CI} 1.53-2.5], P < .001), ulceration by 63% (OR 1.63 [95% CI 1.21-2.18], P < .001), and Clark level IV to V by 48% (OR 1.48 [95% CI 1.19-1.85]). Patients without ulceration but with dermal mitoses had 92% (OR 1.92 [95% CI 1.5-2.48], P < .001) increased SLN positivity. LIMITATIONS: Limited survival data are available. CONCLUSIONS: Younger age, a Breslow thickness >0.8 mm, the presence of dermal mitoses, ulceration, and Clark level IV to V are positive predictors of positive SLN. While the new American Joint Committee on Cancer system has removed dermal mitotic rate from staging, continued evaluation of dermal mitotic rate could be valuable for guiding surgical decision making about SLNB.

Sentinel lymph node biopsy in Merkel cell carcinoma: Predictors of sentinel lymph node positivity and association with overall survival.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive malignancy with high rates of recurrence and metastasis. OBJECTIVE: To evaluate predictors of sentinel lymph node (SLN) positivity in MCC using the National Cancer Database. METHODS: The National Cancer Database, from 2012 to 2014, was used to identify 3048 patients with MCC, of whom 1174 received an SLN biopsy. Predictors of SLN positivity were evaluated using logistic regression. Overall survival was evaluated using a Cox proportional hazards model. RESULTS: Of patients who underwent SLN biopsy, those with primary lesions on the trunk (odds ratio, 1.98; 95% confidence interval [CI], 1.23-3.17; P = .004), tumor-infiltrating lymphocytes (odds ratio, 1.58; 95% CI, 1.01-2.46; P = .04), or lymphovascular invasion (odds ratio, 3.45; 95% CI, 2.51-4.76; P < .001) were more likely to have positive SLNs on multivariate analysis. Overall survival was negatively affected by age ≥75 years (hazard ratio [HR], 2.55; 95% CI, 1.36-4.77; P = .003), male sex (HR, 1.78; 95% CI, 1.09-2.91, P = .022), immunosuppression (HR, 3.51; 95% CI, 1.72-7.13; P = .001), and SLN positivity (HR, 3.15; 95% CI, 1.98-5.04; P < .001). LIMITATIONS: Lack of disease-specific survival and potential selection bias from a retrospective data set. CONCLUSIONS: Truncal MCC, tumor-infiltrating lymphocytes, and presence of lymphovascular invasion were independent predictors of positive SLNs. Overall survival was negatively affected by advancing age, male sex, immunosuppression, and SLN positivity.

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy.

Decreased T-Cell Programmed Death Receptor-1 Expression in Pregnancy-Associated Melanoma.

INTRODUCTION: Pregnancy depends on tolerance of an immunologically foreign fetus through type 1 T-cell suppression. Worse melanoma outcomes have been described within 1 year of childbirth. We assessed immunopathologic factors that may account for the observed negative impact of pregnancy on outcome. MATERIALS AND METHODS: Women of child-bearing age with ≥24 months follow-up were identified from our Institutional Melanoma Registry. Women with available primary tumor blocks were compared [history of childbirth within 1 year of diagnosis (CB1Y) (n = 18) vs. nonpregnant age-matched controls (n = 13)]. Immunohistochemical staining with quantification of immune infiltrates: CD68 tumor-associated macrophages, CD3 tumor-infiltrating T cells, and PD-1 activated/exhausted T cells; and hematolymphangiogenesis: CD31/D2-40 blood vessels and D2-40 lymphatics was performed by 2 blinded dermatopathologists. RESULTS: CB1Y tumors showed decreased CD3 tumor-infiltrating T cells (P < 0.05) with significantly reduced PD1 expression (P ≤ 0.05). The CD3:PD1 ratio was higher in CB1Y (P < 0.05). Other tested parameters did not significantly differ between the 2 groups. DISCUSSION: As PD1 expression is induced during type 1 T-cell activation, these data suggest that immune ignorance or suppression may predominate in CB1Y. Further studies are required to identify interventions that may promote tumor-associated T-cell inflammation in such patients.

Challenges in Microsurgical Reconstruction for Craniofacial Osteomyelitis With Resultant Osteonecrosis.

INTRODUCTION: Chronic osteomyelitis is characterized by compromised blood supply and eventual osteonecrosis. Definitive treatment requires aggressive resection of affected bone. The resultant defect poses a unique challenge to reconstructive surgeons. Much of the literature on craniofacial osteomyelitis focuses on infection eradication, rather than subsequent reconstruction. This article reports representative cases from our experience with free flap reconstruction for defects secondary to chronic osteomyelitis of the craniofacial skeleton. METHODS/RESULTS: The authors selected 5 of the most difficult reconstructive cases of craniofacial osteomyelitis from our experience in a single tertiary referral institution with a follow-up of at least 6 months. Three of the 5 cases arose in the setting of previous head and neck cancer treated with resection and radiation therapy. One case had a previous surgical craniotomy complicated by osteomyelitis and multiple failed alloplastic reconstructions. The final case was due to multiple gunshots to the head, with subsequent cerebral and cranial abscess (>1000cc). In each case, the defect was successfully treated with free tissue transfer. Two cases required creation of recipient vessels with an arteriovenous loop. CONCLUSIONS: Free tissue transfer provides a versatile and effective tool in the reconstruction of extensive craniofacial osteomyelitis defects. Furthermore, the addition of vascularized tissue can protect against further episodes of osteomyelitis. Finally, arteriovenous loops can be employed successfully when prior radiation and infection of the wound bed precludes the use of local recipient target vessels.

Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients.

BACKGROUND: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. METHODS: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. RESULTS: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). CONCLUSIONS: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.