Immune Status in Merkel Cell Carcinoma: Relationships With Clinical Factors and Independent Prognostic Value.

BACKGROUND: Immunosuppression (IS) currently is not considered in staging for Merkel cell carcinoma (MCC). An analysis of the National Cancer Database (NCDB) was performed to investigate immune status as an independent predictor of overall survival (OS) for patients with MCC and to describe the relationship between immune status and other prognostic factors. METHODS: The NCDB was queried for patients with a diagnosis of MCC from 2010 to 2016 who had known immune status. Multivariable Cox proportional hazards models were used to define factors associated with OS. Secondary models were constructed to assess the association between IS etiology and OS. Multivariable logistic regression models were used to characterize relationships between immune status and other factors. RESULTS: The 3-year OS was lower for the patients with IS (44.6%) than for the immunocompetent (IC) patients (68.7%; p < 0.0001). Immunosuppression was associated with increased adjusted mortality hazard (hazard ratio [HR], 2.36, 95% confidence interval [CI], 2.03-2.75). The etiology of IS was associated with OS (p = 0.0015), and patients with solid-organ transplantation had the lowest 3-year OS (32.7%). Immunosuppression was associated with increased odds of greater nodal burden (odds ratio [OR], 1.70; 95% CI, 1.37-2.11) and lymphovascular invasion (OR, 1.58; 95% CI, 1.23-2.03). CONCLUSIONS: Immune status was independently prognostic for the OS of patients with localized MCC. The etiology of IS may be associated with differential survival outcomes. Multiple adverse prognostic factors were associated with increased likelihood of IS. Immune status, and potentially the etiology of IS, may be useful prognostic factors to consider for future MCC staging systems.

An Anatomical Guide to the Terminal Facial Artery: Lumen Diameter and Associated Anatomy Relevant to Dermatologic Procedures.

BACKGROUND: Dermal filler injection in the vicinity of the terminal facial artery (FA) can lead to vascular compromise with devastating consequences, including tissue necrosis, blindness, and stroke. OBJECTIVE: The purpose of this study was to examine lumen diameter and other anatomical features of the terminal FA relevant to dermal filler injection. MATERIALS AND METHODS: Eighteen embalmed adult cadavers were dissected along the distribution of the terminal FA. Gross and microscopic measurements were taken at predetermined points in its course. RESULTS: Mean lumen diameter was largest at the midpoint between the oral commissure and the lateral supra-alar crease (0.81 ± 0.36 mm; point P1) and smallest at the midpoint between the lateral supra-alar crease and the medial canthus (0.43 ± 0.23 mm; point P3). Mean cutaneous depth was deepest at the lateral supra-alar crease (5.06 ± 1.84 mm; point P2) and most superficial at the midpoint between the lateral supra-alar crease and the medial canthus (3.13 ± 2.07 mm; point P3). CONCLUSION: The large-caliber lumen diameter of the terminal FA creates the potential for intra-arterial injection with commonly used filler needles and blunt-tipped cannulas at all points in its course in the nasolabial fold and midface.

Tumor infiltrating lymphocyte grade in Merkel cell carcinoma: relationships with clinical factors and independent prognostic value.

INTRODUCTION: Surrogate markers of the host immune response are not currently included in AJCC staging for Merkel cell carcinoma (MCC), and have not been consistently associated with clinical outcomes. We performed an analysis of a large national database to investigate tumor infiltrating lymphocyte (TIL) grade as an independent predictor of overall survival (OS) for patients with MCC and to characterize the relationship between TIL grade and other clinical prognostic factors. MATERIAL AND METHODS: The NCDB was queried for patients with resected, non-metastatic MCC with known TIL grade (absent, non-brisk and brisk). Multivariable Cox regression modeling was performed to define TIL grade as a predictor of OS adjusting for other relevant clinical factors. Multinomial, multivariable logistic regression was performed to characterize the relationship between TIL grade and other clinical prognostic factors. Multiple imputation was performed to account for missing data bias. RESULTS: Both brisk (HR 0.55, CI 0.36-0.83) and non-brisk (HR 0.77, CI 0.60-0.98) were associated with decreased adjusted hazard of death relative to absent TIL grade. Adverse clinical factors such as 1-3 positive lymph nodes, lymphovascular invasion (LVI) and immunosuppression were associated with increased likelihood of non-brisk TIL relative to absent TIL grade (p values <.05). Extracapsular extension (ECS) was associated with decreased likelihood of brisk TIL relative to absent TIL grade (p<.05). DISCUSSION: Histopathologic TIL grade was independently predictive for OS in this large national cohort. Significant differences in the likelihood of non-brisk or brisk TIL relative to absent grade were present with regards to LVI, ECS and immune status. TIL grade may be a useful prognostic factor to consider in addition to more granular characterization of TIL morphology and immunophenotype.

Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.

BACKGROUND: Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC. METHODS: This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow-up time was 29 months. OS was described using Kaplan-Meier methods and compared for subgroups by immune status and adjuvant RT using log-rank tests, multivariable Cox regression and interaction effect testing. RESULTS: A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54-0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values > 0.05). CONCLUSIONS: In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC.

Lumen Diameter and Associated Anatomy of the Superior Labial Artery With a Clinical Application to Dermal Filler Injection.

BACKGROUND: Vascular compromise and subsequent tissue necrosis is a rare but disfiguring complication of dermal filler injection that frequently occurs in regions of the lip and nasolabial fold supplied by the superior labial artery (SLA). OBJECTIVE: The purpose of this study was to examine lumen diameter and other anatomical features of the SLA relevant to dermal filler injection in the clinical setting. MATERIALS AND METHODS: Eighteen adult cadavers were dissected. Detailed measurements of the SLA were taken at predetermined points along its course. RESULTS: Lumen diameter of the SLA was largest at the labial commissure (0.85 ± 0.34 mm; Point P1) and smallest at the midline (0.56 ± 0.21 mm; Point P4). The deepest mean cutaneous depth of the SLA was at its branch point from the facial artery (5.49 ± 1.95 mm; SLA branch point), whereas the most superficial mean cutaneous depth was at the midpoint between the labial commissure and peak of Cupid's bow (4.29 ± 1.54 mm; Point P2). CONCLUSION: The variable, superficial course of the SLA and its large caliber place it at significant risk for intra-arterial injection with dermal filler at all points along its course.

Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database.

BACKGROUND: We performed an analysis of the National Cancer Database to determine optimal doses of conventionally-fractionated adjuvant radiotherapy for patients with stage I/II or III Merkel cell carcinoma. METHODS: The cohort included 2735 patients with resected Merkel cell carcinoma of the head and neck, trunk or extremities receiving radiotherapy. Exclusion criteria included doses of radiotherapy <30 or >80 Gy, or dose per fraction >200 or <180 cGy. Recursive partitioning analysis and spline models were used to select dose thresholds. Multivariable Cox regression was performed to validate thresholds with respect to overall survival. RESULTS: Recursive partitioning analysis models defined a threshold of 57 Gy for stage I/II Merkel cell carcinoma, above which 3-year overall survival rate was decreased (P < 0.0001). The 3-year overall survival rate for patients receiving 50.0-57.0 Gy (81.2%) was greater compared to doses of 30.0-49.9 Gy (75.3%) or >57.0 Gy (70%, P < 0.0001). Doses > 57.0 Gy were associated with an increased hazard of death (1.31, confidence interval 1.07-1.60) with respect to doses of 50.0-57.0 Gy. Doses < 50.0 Gy for stage III Merkel cell carcinoma were associated with worsened 3-year overall survival (P < 0.0001) and increased hazard of death (2.01, confidence interval 1.43-2.82) with respect to doses between 50.0 and 57.0 Gy. CONCLUSIONS: Our results support doses of 50-57 Gy for most patients with stage I/II Merkel cell carcinoma receiving conventionally-fractionated adjuvant radiotherapy. In contrast to a prior National Cancer Database analysis, our results suggest doses ≥ 50 Gy should be strongly considered for patients with stage III Merkel cell carcinoma regardless of anatomic subsite.

Utility and accuracy of endobronchial ultrasound as a diagnostic and staging tool for the evaluation of mediastinal adenopathy.

BACKGROUND: Endobronchial ultrasound (EBUS) is an emerging technology for mediastinal evaluation which is less invasive than cervical mediastinoscopy, the traditional gold standard. The purpose of our study is to evaluate the utility and accuracy of EBUS as a diagnostic and staging tool at our regional teaching institution. METHODS: We retrospectively reviewed the institutional thoracic surgery database for all patients undergoing EBUS between August, 2008 and March, 2011. RESULTS: 190 patients underwent EBUS. 87 (46 %) patients underwent EBUS for diagnosis only; 73 (38 %) for staging only; and 30 (16 %) for both diagnosis and staging. Diagnoses obtained by diagnostic EBUS included non-small cell lung cancer--n = 36 (31 %); other cancer--n = 22 (19 %); sarcoid/granulomatous--n = 8 (7 %); benign lymphoid tissue--n = 50 (43 %); and was nondiagnostic in one case (1 %). For staging EBUS 53 (51 %) patients had benign lymph node tissue. 103 patients had a benign result at the time of EBUS. Fifty-six (54 %) of these patients underwent subsequent mediastinal lymph node dissection or mediastinoscopy for tissue confirmation with the remainder undergoing follow up surveillance chest CT scans. Two patients had a false negative EBUS. Both false negative studies sampled levels 4L, 4R, and 7. The overall false negative rate was 2 % for all benign results, and 4 % for those benign results confirmed with lymph node dissection or mediastinoscopy. The sensitivity and specificity of diagnostic EBUS was 97 and 100 %. The sensitivity and specificity for staging EBUS was 98 and 100 %. In those patients (n = 103) undergoing a staging EBUS, a mean of 2.6 nodal stations were sampled, with 59 % (n = 61) of these patients having three lymph node stations sampled and 33 % (n = 30) had two lymph node stations sampled. CONCLUSION: We found that EBUS is a highly accurate and minimally invasive manner in which to both diagnose mediastinal masses and stage the mediastinum.