Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy.

BACKGROUND: A 31-gene genetic expression profile (31-GEP; Class 1 = low risk, Class 2 = high risk) developed to predict outcome in cutaneous melanoma (CM) has been validated by retrospective, industry-sponsored, or small series. METHODS: Tumor features, sentinel node biopsy (SNB) results, and outcomes were extracted from a prospective database of 383 C M patients who underwent SNB and had a 31-GEP run on their primary tumor. Groups were compared by uni- and multi-variable analysis. Relapse-free and distant metastasis-free survival (RFS, DMFS) were estimated by Kaplan-Meier method. RESULTS: Breslow thickness, T stage, and SNB positivity were significantly higher in Class 2 patients. Recurrence rates were higher for Class 2 vs Class 1 patients and highest in patients who were Class 2 and SNB positive. GEP class was predictive of RFS and DMFS and independently predicted relapse in AJCC "low risk" (stages IA-IIA) patients. CONCLUSIONS: 31-GEP adds prognostic information in CM patents undergoing SNB.

Relationship of patient age to tumor factors and outcomes among patients undergoing sentinel node biopsy for melanoma.

INTRODUCTION: Patient age has been intermittently associated with demographics and outcomes in cutaneous melanoma. We looked at the association of age and patient demographics, tumor features, and melanoma-related outcomes in patients undergoing sentinel lymph node (SLN) biopsy for melanoma. METHODS: We reviewed demographics (age, gender), tumor features (mean Breslow thickness, ulceration, SLN positivity rates), and outcomes (all-site relapse, progression to stage IV, death from melanoma, complications) from a university-based prospective database of 1633 patients. Patients were grouped by decade of age and the impact of age was examined by univariable and multivariable analyses. RESULTS: Increasing age was directly associated with number of patients referred for SLN biopsy, male gender, head and neck (H&N) tumor location, mean Breslow thickness, tumor ulceration, and with all -site relapse, progression to stage IV, death from melanoma and complication rates. Increasing age was indirectly associated with SLN positivity rates. Comparing ages <30 with ages >60, these trends reached statistical significance for male gender, H&N location, SLN positivity, all-site relapse, progression to stage IV (development of metastases) and death from melanoma. CONCLUSIONS: Referrals for SLN biopsy increase with increasing patient age, yet increasing age is associated with lower SLN positivity rates. This occurs despite the fact that older patients have thicker, more ulcerated tumors, and higher melanoma-related relapse and death rates.

Reduction of lymphocele rate in patients undergoing sentinel node biopsy for melanoma by intraoperative placement of plant-based hemostatic powder: Results of a prospective trial.

BACKGROUND: Lymphocele is a complication of sentinel node biopsy (SNB) for melanoma. Plant-based hemostatic powder (PBHP) may have a lymphostatic benefit. We studied whether PBHP placed intraoperatively could reduce lymphocele rates. METHODS: We performed an open label, prospective, IRB -approved, before- and-after, matched control trial of PBHP placed into the wound in patients undergoing SNB of groin or axillary nodes for melanoma staging. Patient/tumor features and lymphocele rates were compared by standard statistical tests. RESULTS: 66 control and 66 treatment (49 axillary and 17 groin in each arm) SNBs were performed in 61 and 55 patients, respectively, for a total 132 SNBs in 116 patients. Patient and tumor features were similar between groups. Nineteen lymphoceles occurred (14.4%); lymphocele rates were 22.2% (14/66) in the control group and 7.6% (5/66) in the treatment group (p = 0.026). The reduction in lymphocele rates between arms was greater for axillary than for groin sites (87.5% vs. 33%); the axillary reduction was statistically significant (p = 0.030). CONCLUSIONS: Intra-operative placement of PBHP reduced the rate of lymphoceles in patients undergoing SNB for melanoma.

Impact of Gene Expression Profiling on Decision-Making in Clinically Node Negative Melanoma Patients after Surgical Staging.

INTRODUCTION: The surgeon's role in the follow-up of pathologic stage I and II melanoma patients has traditionally been minimal. Melanoma genetic expression profile (GEP) testing provides binary risk assessment (Class 1-low risk, Class 2-high risk), which can assist in predicting metastasis and formulating appropriate follow up. We sought to determine the impact of GEP results on the management of clinically node negative cutaneous melanoma patients staged with sentinel lymph node biopsy (SLNB). METHODS: A retrospective review of prospectively gathered data consisting of patients seen from September 2015 - August 2016 was performed to determine whether GEP class influenced follow-up recommendations. Patients were stratified into four groups based on recommended follow-up plan: Dermatology alone, Surgical Oncology, Surgical Oncology with recommendation for adjuvant clinical trial, or Medical and Surgical Oncology. RESULTS: Of ninety-one patients, 38 were pathologically stage I, 42 stage II, 10 stage III, and 1 stage IV. Combining all stages, GEP Class 1 patients were more likely to be followed by Dermatology alone and less like to be followed by Surgical Oncology with recommendation for adjuvant trial compared to Class 2 patients (P less than 0.001). Among stage 1 patients, Class 1 were more likely to follow up with Dermatology alone compared to Class 2 patients (82 vs. 0%; P less than 0.001). Among stage II patients, GEP Class 1 were more likely to follow up with Dermatology alone (21 vs 0%) and more Class 2 patients followed up with surgery and recommendations for adjuvant trial (36 vs 64%; P less than 0.05). There was no difference in follow up for stage III patients based on the GEP results (P=0.76). CONCLUSION: GEP results were significantly associated with the management of stage I-II melanoma patients after staging with SLNB. For node negative patients, Class 2 results led to more aggressive follow up and management. J Drugs Dermatol. 2018;17(2):196-199.

Patients with sentinel lymph node positive melanoma: Who needs completion lymph node dissection?

INTRODUCTION: Completion lymph node dissection (CLND) for melanoma after positive sentinel lymph node biopsy (SLNB) was recently shown to improve regional but not overall survival, likely due to the majority of patients harboring no further nodal disease. We sought to determine predictors of non-sentinel node (NSN) positivity. METHODS: Retrospective review of prospectively collected data on melanoma patients undergoing SLNB. RESULTS: 116 patients underwent 119 CLNDs. The incidence of NSN positivity was 17.6%; the average number of positive NSNs in those cases was 1.5. Cervical and inguinofemoral location were most likely to yield positive NSN(s) (40% each). Conversely, the axilla was least likely at 18% (p < 0.001). The average number of nodes harvested was 13 for NSN negative cases and 20 for NSN positive cases (p = 0.005). Tumor thickness increased the probability of positive NSN(s) (OR 1.2, p = 0.02). CONCLUSIONS: Tumor thickness and nodal basin were predictors of NSN metastasis, factors that could help determine which patients may benefit from CLND. Further, CLNDs with fewer nodes may inadequately clear residual nodal disease.

Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?

OBJECTIVE: There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. METHODS: Retrospective review of a prospectively collected multi-institutional melanoma database. RESULTS: Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. CONCLUSIONS: PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.

Nonvisualized sentinel lymph nodes on lymphoscintigraphy in melanoma: predictive factors and surgical outcomes.

PURPOSE: Preoperative lymphoscintigraphy is the standard for the identification of sentinel lymph nodes (SLNs) in melanoma. The impact of negative scintigraphy [nonvisualization (NV) of the SLN] on surgical outcomes is inadequately reported in the literature. The objectives of this study were to determine the incidence, predictive factors, and surgical outcomes of NV in clinically node-negative melanoma patients. PATIENTS AND METHODS: A retrospective review of a prospective, Institutional Review Board approved, melanoma sentinel node database from January 2005 to August 2015 was performed. RESULTS: Twenty-seven of the 897 (3%) patients had negative scintigraphy. Single-photon emission computed tomography/computed tomography was performed in addition to planar imaging in four patients and failed to locate the SLN in all cases. NV was associated with older age (71 vs. 59 years, P<0.001), head and neck primaries (41%), and previous operations adjacent to the primary tumor or nodal beds (37%). NV was not associated with sex, BMI, or T stage. Despite a negative scintigram, the SLN was still found at operation in 10 of the 27 (37%) patients using the hand-held gamma probe, with one (10%) patient having nodal metastasis. Two patients with NV had nodal recurrence, with a mean follow-up of 3 years. DISCUSSION: Preoperative lymphoscintigraphy in clinically node-negative melanoma patients is associated with a low NV rate. Predictors for NV include age, head and neck location, and previous operations at adjacent sites. NV should not preclude surgical exploration as the SLN can still be found at operation in over one-third of patients.

Hard Copy Durable Patient Cancer Education Materials: Do They Still Matter?

Traditional hard copy information materials are still present in our cancer clinics. While their actual impact on patient care often goes un-assessed, it is important to understand their role in today's electronic age where information can easily be obtained from various sources. It has remained the practice in our melanoma clinic to provide an information booklet to all of our new patients. The purpose of this study was to evaluate how useful this booklet was, as well as determine the current resources our patients use to gather cancer information. All patients referred to the clinic in the previous 3 years were pooled from our prospective, IRB-approved, melanoma sentinel node database. Of these 205 patients, a valid email address was listed for 147. A ten-question survey was emailed to all of these patients, who were not told ahead of time that their experience with the booklet would be studied. Seventy-seven of the 147 (52 %) patients polled responded. Fifty-eight (75 %) remembered receiving the booklet at their initial consultation. Forty-four (76 %) of those patients rated it as extremely or very useful, and no patients reported the booklet as not useful at all. Eighty-eight percent of respondents found the information to be clear and helpful. Sixty-four percent remembered the provider reviewing the material with them, and nearly all of these patients found that helpful. When asked to rank the importance of the various resources for obtaining cancer information, providers were ranked as most important, followed by the information booklet and Internet information sites. Internet blogs and friends and family were rated as the least important sources of information. Even in the current electronic age, our results indicate that information shared by providers, including the hard copy education booklet, was the most important source of information for our newly referred melanoma patients.

Axillary web syndrome: an underappreciated complication of sentinel node biopsy in melanoma.

OBJECTIVE: Axillary web syndrome (AWS) is known to occur after axillary dissection and has been reported after axillary sentinel lymph node biopsy (ASLNB) for breast cancer. However, the incidence and outcomes of AWS after ASLNB for melanoma are unknown. METHODS: A retrospective review of prospectively collected, clinically node-negative patients undergoing ASLNB for melanoma at a single institution during a 14-year period was conducted to determine the incidence of AWS. Features pertaining to patients (age and gender), primary tumor (location, Breslow's depth), and nodes (number removed, positive node rate) were correlated with the occurrence of AWS. RESULTS: Of the 465 patients undergoing ASLNB, 21 (4.5%) developed AWS postoperatively. In comparison, the incidence of other complications in this population were infection 3%, bleeding 1.5%, wound dehiscence .8%, lymphocele 5%, and lymphedema .4%. There was no statistical difference between patients with or without AWS in terms of tumor thickness, location of primary (upper extremity vs trunk), average number of sentinel nodes removed, positive SLNB rates (10% vs 12%), patient age, or gender. All cases of AWS resolved with expectant management; none required surgical intervention. CONCLUSIONS: AWS is a notable complication of ASLNB for melanoma, with an incidence as high or higher than "standard" complications. AWS should, therefore, be included in the preoperative discussion of possible complications of ASLNB. Traditional patient, tumor, and nodal factors are not predictive of AWS. Patients should be counseled that AWS usually responds to symptomatic treatment and resolves with time.

Merkel cell carcinoma: what makes a difference?

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor that may spread via lymphatics and can therefore be staged with sentinel lymph node biopsy (SLNB). MCC is radiosensitive and chemosensitive, although the role of adjuvant therapy is still unclear. We examined the impact of different treatments on the outcome of MCC. METHODS: We performed a retrospective review of state cancer registry data from California, Oregon, and Washington of patients diagnosed with primary skin MCC between 1988 and 2012 (n = 4,038). Data were analyzed using Cox regression and Kaplan-Meier methods to examine disease-specific survival. RESULTS: Patients with positive nodes or no documented nodal evaluation had worse survival compared with node-negative patients. No nodal evaluation had decreased survival compared with lymph node evaluation by SLNB. Completion lymph node dissection conferred improved survival in patients with a positive SLNB. In clinically node-negative patients who had a positive SLNB, radiation and chemotherapy did not affect survival. CONCLUSIONS: Lymph node evaluation is an important component to MCC treatment. The role of adjuvant radiation and chemotherapy needs further evaluation.

Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

BACKGROUND: The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. METHODS: A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. RESULTS: Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. CONCLUSIONS: Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management.

Effect of biopsy type on outcomes in the treatment of primary cutaneous melanoma.

BACKGROUND: Surgical excision remains the primary and only potentially curative treatment for melanoma. Although current guidelines recommend excisional biopsy as the technique of choice for evaluating lesions suspected of being primary melanomas, other biopsy types are commonly used. We sought to determine the impact of biopsy type (excisional, shave, or punch) on outcomes in melanoma. METHODS: A prospectively collected, institutional review board-approved database of primary clinically node-negative melanomas (stages cT1-4N0) was reviewed to determine the impact of biopsy type on T-staging accuracy, wide local excision (WLE) area (cm(2)), sentinel lymph node biopsy (SLNB) identification rates and results, tumor recurrence, and patient survival. RESULTS: Seven hundred nine patients were diagnosed by punch biopsy (23%), shave biopsy (34%), and excisional biopsy (43%). Shave biopsy results showed significantly more positive deep margins (P < .001). Both shave and punch biopsy results showed more positive peripheral margins (P < .001) and a higher risk of finding residual tumor (with resulting tumor upstaging) in the WLE (P < .001), compared with excisional biopsy. Punch biopsy resulted in a larger mean WLE area compared with shave and excisional biopsies (P = .030), and this result was sustained on multivariate analysis. SLNB accuracy was 98.5% and was not affected by biopsy type. Similarly, biopsy type did not confer survival advantage or impact tumor recurrence; the finding of residual tumor in the WLE impacted survival on univariate but not multivariate analysis. CONCLUSIONS: Both shave and punch biopsies demonstrated a significant risk of finding residual tumor in the WLE, with pathologic upstaging of the WLE. Punch biopsy also led to a larger mean WLE area compared with other biopsy types. However, biopsy type did not impact SLNB accuracy or results, tumor recurrence, or disease-specific survival (DSS). Punch and shave biopsies, when used appropriately, should not be discouraged for the diagnosis of melanoma.