Sentinel lymph node positivity in melanoma: Which risk prediction tool is most accurate?

BACKGROUND: Sentinel lymph node biopsy for melanoma determines treatment and prognostic factors and improves disease-specific survival. To risk-stratify patients for sentinel lymph node biopsy consideration, Memorial Sloan Kettering Cancer Center and Melanoma Institute Australia developed nomograms to predict sentinel lymph node positivity. We aimed to compare the accuracy of these 2 nomograms. METHODS: A multi-institutional study of patients with melanoma receiving sentinel lymph node biopsy between September 2018 and December 2022 was performed. The accuracy of the 2 risk prediction tools in determining a positive sentinel lymph node biopsy was analyzed using receiver operating characteristic curves and area under the curve. RESULTS: In total, 532 patients underwent sentinel lymph node biopsy for melanoma; 98 (18.4%) had positive sentinel lymph node. Increasing age was inversely related to sentinel lymph node positivity (P < .01); 35.7% of patients ≤30 years had positive sentinel lymph node compared with 9.7% of patients ≥75 years. When we analyzed the entire study population, accuracy of the 2 risk prediction tools was equal (area under the curveMemorial Sloan Kettering Cancer Center: 0.693; area under the curveMIA: 0.699). However, Memorial Sloan Kettering Cancer Center tool was a better predictor in patients aged ≥75 years (area under the curveMemorial Sloan Kettering Cancer Center: 0.801; area under the curveMelanoma Institute Australia: 0.712, P < .01) but Melanoma Institute Australia tool performed better in patients with a higher mitotic index (mitoses/mm2 ≥2; area under the curveMemorial Sloan Kettering Cancer Center: 0.659; area under the curveMelanoma Institute Australia: 0.717, P = .027). Both models were poor predictors of sentinel lymph node positivity in young patients (age ≤30 years; area under the curveMemorial Sloan Kettering Cancer Center: 0.456; area under the curveMelanoma Institute Australia: 0.589, P = .283). CONCLUSION: The current study suggests that the 2 risk stratification tools differ in their abilities to predict sentinel lymph node positivity in specific populations: Memorial Sloan Kettering Cancer Center tool is a better predictor for older patients, whereas Melanoma Institute Australia tool is more accurate in patients with a higher mitotic index. Both nomograms performed poorly in predicting sentinel lymph node positivity in young patients.

Factors Associated With Upstaging of Melanoma Thickness on Final Excision.

INTRODUCTION: The incidence and risk factors associated with upstaging from initial biopsy to definitive excision in cutaneous melanoma have not been established. The aim of this study was to determine the incidence of tumor stage upstaging and associated risk factors using the National Cancer Database. METHODS: A retrospective study of the National Cancer Database between 2012 and 2016 was performed. The cohort of patients undergoing excision of melanoma with available data comprised 133,592 patients. Differences in characteristics for upstaging were determined using Wilcox rank-sum, chi-square, or Fisher's exact tests. Multivariable analysis was performed using logistic regression to determine factors associated with upstaging. RESULTS: Incidence of upstaging was 5.2%. Upstaged patients were older, male, of non-White race, and of lower education level (P < 0.001). Lesions of the head/neck and lower extremity had increased incidence of upstaging compared to the trunk (P < 0.001). Nodular and acral lentiginous melanoma was associated with higher incidence of upstaging compared to superficial spreading melanoma (P < 0.001). Patients with lymphovascular invasion had increased risk of upstaging (P < 0.001). CONCLUSIONS: Upstaging of melanoma is infrequent but is significantly more prevalent in non-White patients and those with lower educational status. Provider and patient education should include the higher risk of upstaging in these groups and the possible need for further surgical intervention, such as re-excision of margins and sentinel lymph node biopsy.

COVID-19 is Affecting the Presentation and Treatment of Melanoma Patients in the Northeastern United States.

BACKGROUND: Covid-19 significantly affected healthcare delivery over the past year, with a shift in focus away from nonurgent care. Emerging data are showing that screening for breast and colon cancer has dramatically decreased. It is unknown whether the same trend has affected patients with melanoma. METHODS: This is a retrospective cohort study of melanoma patients at two large-volume cancer centers. Patients were compared for 8 months before and after the lockdown. Outcomes focused on delay in treatment and possible resultant upstaging of melanoma. RESULTS: A total of 375 patients were treated pre-lockdown and 313 patients were treated post-lockdown (17% decrease). Fewer patients presented with in situ disease post-lockdown (15.3% vs. 17.9%), and a higher proportion presented with stage III-IV melanoma (11.2% vs. 9.9%). Comparing patients presenting 2 months before versus 2 months after the lockdown, there was an even more significant increase in Stage III-IV melanoma from 7.1% to 27.5% (p < 0.0001). Finally, in Stage IIIB-IIID patients, there was a decrease in patients receiving adjuvant therapy in the post lockdown period (20.0% vs. 15.2%). CONCLUSIONS: As a result of the recent pandemic, it appears there has been a shift away from melanoma in situ and toward more advanced disease, which may have significant downstream effects on prognosis and could be due to a delay in screening. Significantly patients have presented after the lockdown, and fewer patients are undergoing the recommended adjuvant therapies. Patient outreach efforts are essential to ensure that patients continue to receive preventative medical care and screening as the pandemic continues.

Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction.

National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time. We hypothesized that integrating clinicopathologic features with the 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more precise SLN risk prediction. METHODS: An integrated 31-GEP (i31-GEP) neural network algorithm incorporating clinicopathologic features with the continuous 31-GEP score was developed using a previously reported patient cohort (n = 1,398) and validated using an independent cohort (n = 1,674). RESULTS: Compared with other covariates in the i31-GEP, the continuous 31-GEP score had the largest likelihood ratio (G2 = 91.3, P < .001) for predicting SLN positivity. The i31-GEP demonstrated high concordance between predicted and observed SLN positivity rates (linear regression slope = 0.999). The i31-GEP increased the percentage of patients with T1-T4 tumors predicted to have < 5% SLN-positive likelihood from 8.5% to 27.7% with a negative predictive value of 98%. Importantly, for patients with T1 tumors originally classified with a likelihood of SLN positivity of 5%-10%, the i31-GEP reclassified 63% of cases as having < 5% or > 10% likelihood of positive SLN, for a more precise, personalized, and clinically actionable SLN-positive likelihood estimate. CONCLUSION: These data suggest the i31-GEP could reduce the number of SLNBs performed by identifying patients with likelihood under the 5% threshold for performance of SLNB and improve the yield of positive SLNBs by identifying patients more likely to have a positive SLNB.

Simultaneous primary invasive breast carcinoma and ipsilateral cutaneous melanoma of the back: Surgical approach and considerations, a case report.

INTRODUCTION AND IMPORTANCE: A patient presented with ipsilateral, synchronous primary malignancies of left upper back melanoma and left breast invasive ductal carcinoma. This complex presentation was managed with a multidisciplinary approach. CASE PRESENTATION: A 61-year-old female presented with multiple cutaneous lesions, revealed to be several foci of melanoma in situ as well as a T4b melanoma of the left upper back. On staging work up, a left breast malignancy was incidentally discovered. Genetic testing did not delineate a relevant mutation to explain the synchronous malignancies. Multidisciplinary surgical planning entailed consideration of the lymphatic drainage patterns of the lesions, with both the upper back melanoma and breast carcinoma expected to drain to the left axilla. Ultimately, simultaneous resections of both malignancies were performed as well as concomitant left sentinel lymph node biopsies utilizing dual tracer technique. CLINICAL DISCUSSION: Currently, cases of synchronous primary cutaneous melanoma and independent, ipsilateral primary breast carcinoma have not been examined, and thus surgical considerations for axillary staging in this circumstance have not been discussed. The existing literature instead explores the incidence and operative challenges of one malignancy following the other after an interval of time. CONCLUSION: This case highlights the utility of a multidisciplinary team for complex oncologic presentations and discusses a creative surgical approach to address two simultaneous primary malignancies involving the left breast and ipsilateral skin of the back. This case emphasizes an exceedingly rare presentation and serves as an important example to educate medical professionals on the innovative and team-based approach to treatment.

Evaluation of a Gene Expression Profiling Assay in Primary Cutaneous Melanoma.

BACKGROUND: A significant proportion of deaths from cutaneous melanoma occur among patients with an initial diagnosis of stage 1 or 2 disease. The Decision-Dx Melanoma (DDM) 31-gene assay attempts to stratify these patients by risk of recurrence. This study aimed to evaluate this assay in a large single-institution series. METHODS: A retrospective chart review of all patients who underwent surgery for melanoma at a large academic cancer center with DDM results was performed. Patient demographics, tumor pathologic characteristics, sentinel node status, gene expression profile (GEP) class, and recurrence-free survival (RFS) were reviewed. The primary outcomes were recurrence of melanoma and distant metastatic recurrence. RESULTS: Data from 361 patients were analyzed. The median follow-up period was 15 months. Sentinel node biopsy was performed for 75.9% (n = 274) of the patients, 53 (19.4%) of whom tested positive. Overall, 13.6% (n = 49) of the patients had recurrence, and 8% (n = 29) had distant metastatic recurrence. The 3- and 5-year RFS rates were respectively 85% and 75% for the class 1A group, 74% and 47% for the class 1B/class 2A group, and 54% and 45% for the class 2B group. Increased Breslow thickness, ulceration, mitoses, sentinel node biopsy positivity, and GEP class 2B status were significantly associated with RFS and distant metastasis-free survival (DMFS) in the univariate analysis (all p < 0.05). In the multivariate analysis, only Breslow thickness and ulceration were associated with RFS (p < 0.003), and only Breslow thickness was associated with DMFS (p < 0.001). CONCLUSION: Genetic profiling of cutaneous melanoma can assist in predicting recurrence and help determine the need for close surveillance. However, traditional pathologic factors remain the strongest independent predictors of recurrence risk.

Concomitant Aorto-Caval Reconstruction for Inferior Vena Cava Leiomyosarcoma.

BACKGROUND: Leiomyosarcoma of the inferior vena cava (IVC) is a rare smooth muscle neoplasm typically presenting in the fifth to sixth decades of life with both intraluminal and extraluminal growth patterns. Surgical resection remains the gold standard for nonmetastatic disease and often requires vascular reconstruction. We present an atypical case of leiomyosarcoma involving both the IVC and infrarenal abdominal aorta necessitating reconstruction with intraoperative veno-venous bypass. METHODS: A 63-year-old man initially presenting with back pain was found to have a large mass adjacent to the IVC on MRI, subsequently confirmed to be leiomyosarcoma by biopsy. After 6 months of neoadjuvant chemotherapy, the patient was taken for resection. However, intraoperatively the tumor was found to involve the aorta necessitating combined aorto-caval reconstruction. To facilitate en-bloc resection of the tumor, the aorta was reconstructed first followed by the inferior vena cava using veno-venous bypass. RESULTS: Postoperatively, the patient was taken to the intensive care unit for resuscitation and had an uncomplicated hospital course. He was discharged to rehab 6 days postoperatively and at one year remains free of significant tumor burden with patent aorto-caval bypass grafts. CONCLUSIONS: Primary leiomyosarcoma of the IVC is estimated to have aortic involvement in <10% of cases and concurrent aorto-caval reconstruction can be a well-tolerated option in good surgical candidates. Furthermore, veno-venous bypass can be a useful tool for accomplishing successful oncologic resections. With interdisciplinary collaboration between surgical oncologists, urologists, and vascular surgeons, difficult pathologies can be addressed with good patient outcomes.

Esophagectomy for cancer in octogenarians: should we do it?

PURPOSE: Inconsistent data exists regarding esophagectomy outcomes in octogenarians undergoing transhiatal esophagectomy for esophageal cancer. METHODS: A retrospective review was performed for esophagectomy cancer patients between 2000 and 2012 at our tertiary referral center. Outcome data for octogenarians was compared to younger patients aged 20 to 79 years. A case-matched group of patients younger than 80 years old (n = 33) was included based on the Charlson comorbidity index with the octogenarian group (n = 33). Endpoints included operative morbidity and mortality as well as short- and long-term survival. RESULTS: Thirty-three octogenarians met inclusion criteria. The median age was 82 years, and 79% were male; 76% had adenocarcinoma, 87% had distal esophageal, and 52% had poorly differentiated tumors. Stages 0 through III were observed in 6, 18, 27, and 48% of octogenarians, respectively. Neoadjuvant therapy was administered to 70% of patients, with 48% experiencing downstaging. Transhiatal esophagectomy was performed in 82% of patients, with R0 resection in 94%. The mean hospital stay was 18 days, with morbidity and mortality rates 56 and 9%, respectively, not significantly different from 13-day hospital stay, 45% morbidity, and 9% mortality in younger patients. Cardiac, pulmonary, and surgical site complications occurred in 24, 27, and 6% of octogenarians, respectively. Anastomotic leak occurred in 18% and reoperations in 3%. The median, 3-year survival, and 5-year survival were 21 months, 55.9%, and 37.1%, respectively. Overall survival was worse for octogenarians (p < 0.001). CONCLUSIONS: Postoperative mortality, morbidity, and length of stay in octogenarians are comparable to younger patients, while the overall survival is worse. With appropriate patient selection, good outcomes can be accomplished in octogenarians undergoing esophagectomy for cancer.

Surgical Management of Melanoma.

The surgical management of melanoma has undergone considerable changes over the past several decades, as new strategies and treatments have become available. Surgeons play a pivotal role in all aspects of melanoma care: diagnostic, curative, and palliative. There is a high potential for cure in patients with early-stage melanoma and the selection of an appropriate operation is very important for this reason. Staging the nodal basin has become widespread since the adoption of sentinel lymph node biopsy (SLNB) for the management of melanoma. This operation provides the best prognostic information that is currently available for patients with melanoma. The surgeon plays a central role in the palliation of symptoms resulting from nodal disease and metastases, as melanoma has a propensity to spread to almost any site in the body.

Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma.

Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment.

Developments in the treatment of locally advanced and metastatic squamous cell carcinoma of the skin: a rising unmet need.

Squamous cell carcinoma of the skin (SCCS) is a common malignancy with potentially devastating consequences in patients with locally advanced or metastatic disease. Its rising incidence, primarily a result of an aging population and increased ultraviolet (UV) radiation exposure, characterize an emerging unmet need. A firm understanding of the biology of this disease, likely distinct from that of other squamous malignancies because of the influence of UV radiation, is necessary in the evaluation of treatment paradigms. Careful recognition of high-risk features pertaining to tumor and host characteristics is paramount to proper management. However, a lack of standardization in guidelines in this regard creates a challenge for physicians. Questions persist regarding additional evaluation and treatment for advanced disease such as the roles for sentinel lymph node biopsy and the adjuvant use of radiation and chemotherapy. With respect to advanced disease, multiple combinations of chemotherapy have been tested with variable success, but no rigorous randomized studies have been conducted. In addition, EGFR inhibitors such as cetuximab and erlotinib have displayed antitumor activity and as such, warrant further investigation. In sum, the treatment of locally advanced and metastatic SCCS is a ripe area for clinical investigation. This article summarizes the current understanding of disease biology and emerging questions in the management of this disease.

Tracheobronchial injury in the setting of an esophagectomy for cancer: postoperative discovery a bad omen.

BACKGROUND: A tracheobronchial injury is an uncommon complication of an esophagectomy. Differences in outcomes may exist for patients with injuries detected intraoperatively and postoperatively. METHODS: A retrospective review was performed for patients who underwent an esophagectomy for cancer at Jackson Memorial Hospital/University of Miami from January 2000 to June 2012. RESULTS: An injury to the tracheobronchial tree occurred in 7 of 425 patients (1.6%). The majority of the operations were performed via a transhiatal approach (87.8%). Patients with airway injuries were older (median 73 vs. 63), more likely to have squamous cell carcinoma (85.7% vs. 17.9%), and with proximal tumors (85.7% vs. 14.1%). When given, the type of neoadjuvant treatment consisted of chemoradiotherapy in all patients who suffered an injury, whereas it was only administered to 21.3% of patients without an injury. There were no deaths among three patients in whom the injury was identified intraoperatively. Mortality occurred in three of four patients (75.0%) with an injury detected postoperatively. CONCLUSIONS: Patients with proximal tumors and radiation administration as a component of neoadjuvant treatment are more likely to suffer a tracheobronchial injury. An aggressive reoperative approach is warranted in patients with injuries that are discovered postoperatively.

Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease.

BACKGROUND AND OBJECTIVES: Discovery of incidental gallbladder cancer (IGC) has become more frequent due to adoption of laparoscopy. Gallbladder spillage during operation can disseminate cancer and worsen the prognosis. METHODS: Patients who underwent laparoscopic or open cholecystectomy for benign gallbladder disease January 1996 to August 2011 at two tertiary care facilities were reviewed. Unmatched controls were randomly selected in 2:1 ratio. Preoperative variables were compared between the two groups. RESULTS: Sixty-seven patients with IGC were identified and compared to 134 controls. Mean age was 68 for index cases and 49 for controls; 70% of cases and 75% of controls were female. Multivariate analysis showed that higher risk of IGC was significantly associated with age ≥ 65 (OR = 10.61, P < 0.0001), dilated bile ducts (OR = 4.76, P = 0.0028), and presence of gallbladder wall thickening (OR = 4.39, P = 0.0003). This model yielded a very good area under the curve of receiver operating characteristic (AUC = 0.83) for discriminating the patients with IGC from controls. CONCLUSIONS: IGC is more likely to be found in patients when age is ≥65, with dilated bile ducts and gallbladder wall thickening. Preoperative suspicion of gallbladder cancer should prompt the surgeon to be more careful not to perforate the gallbladder during laparoscopic approach, and to have a lower threshold for conversion if necessary.

Adjuvant therapy of gastrointestinal stromal tumors.

PURPOSE OF REVIEW: The treatment of gastrointestinal stromal tumors (GISTs) with tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib, has produced improved outcomes and survival. However, patients with high-risk tumors still have unacceptably high rates of recurrence and disease progression. In the current review, we examine the various strategies for optimizing the treatment of GISTs. RECENT FINDINGS: Extended duration of treatment (36 months) with adjuvant imatinib resulted in improved recurrence-free survival and overall survival, whereas discontinuation of the TKI led to relapse of disease in most high-risk patients. High-dose therapy of imatinib was beneficial for patients with KIT exon 9 mutations. Patients with KIT exon 11 mutations experienced the most improvement in outcomes from adjuvant imatinib. SUMMARY: The extended duration of TKI treatment, dose optimization, mutation status, and the effects of TKI discontinuation have recently been examined in more detail. As our understanding of TKI therapy grows, an individualized approach to each patient should lead to better outcomes.

Role of sentinel lymphadenectomy in thin cutaneous melanomas with positive deep margins on initial biopsy.

INTRODUCTION: Breslow thickness (BRES) on initial melanoma biopsy determines need for sentinel lymph node (SLN) biopsy. In presence of positive deep margins, BRES is indeterminate. We hypothesized that thin (BRES <0.76 mm) melanomas with positive deep margins and thicker melanomas (BRES 0.76-2.0 mm) have statistically similar risk of SLN metastasis. METHODS: Retrospective review was performed of adult patients undergoing wide excision plus SLN biopsy for melanoma from 01/2004 to 05/2010. Group 1 (BRES <0.76 mm and positive deep margins) was compared to Group 2 (BRES 0.76-2.0 mm, regardless of margin status). Primary outcome was presence of SLN metastasis. RESULTS: 260 patients were eligible, 72 (28%) in Group 1 and 188 (72%) in Group 2. Average age was 57 years, with 120 (46%) females. SLNs were positive in 6/72 (8.3%) patients in Group 1 and 17/188 (9.0%) patients in Group 2 (P=0.86). The two groups were not statistically different by multivariate analysis (P=0.49). In multivariate model, Clark's level IV (P=0.009) was only predictive factor of SLN metastasis. CONCLUSIONS: Melanoma patients with thin BRES but positive deep margins carry risk of SLN metastasis similar to patients with thicker melanomas. Positive deep margins should be considered in decision to perform SLN biopsy. Clark's level IV was significantly associated with SLN metastasis.

Laparoscopic splenectomy: outcome and efficacy for massive and supramassive spleens.

BACKGROUND: Massive and supramassive splenomegaly are relative contraindications to pure laparoscopic splenectomy (LS). METHODS: A retrospective review of adult patients was conducted for splenectomy occurring from 1999 to 2009. Massive and supramassive spleens were defined as craniocaudad length ≥ 17 cm or weight ≥ 600 g and craniocaudad length ≥ 22 cm or weight ≥ 1,600 g, respectively. RESULTS: LS was done for 22 and open splenectomy for 21 patients, of which 12 and 14 were supramassive. Spleen weight and craniocaudad length were comparable. LS was associated with lower blood loss (308 vs 400 mL, P = .24), shorter length of stay (3 vs 4.5 days, P = .054), and similar morbidity (17% vs 14%). Two reoperations and 1 death occurred with open splenectomy. Operative times were longer for LS (195 vs 105 min, P = .008), while the conversion rate was 25%. CONCLUSIONS: In cases of massive and supramassive splenomegaly, better outcomes are accomplished with LS than open splenectomy, and are comparable to hand-assisted LS.

Identification of accessory spleens during laparoscopic splenectomy is superior to preoperative computed tomography for detection of accessory spleens.

BACKGROUND: Missed accessory spleen (AcS) can cause recurrence of hematologic disease after splenectomy. The objective of the study was to determine whether detection of AcS is more accurate with preoperative computed tomography (CT) scan or with exploration during laparoscopic splenectomy. METHODS: A retrospective chart review was performed for 75 adult patients who underwent laparoscopic splenectomy for various hematologic disorders from 1999 to 2009. Preoperative CT scans were performed in all patients. Patients were followed for recurrence of disease, and a scintigraphy scan was performed in those with suspected missed AcS. RESULTS: The most common diagnosis was idiopathic thrombocytopenic purpura in 29 patients (39%), followed by non-Hodgkin's lymphoma in 22 patients (29%). Sixteen AcSs were found during surgery in 15 patients (20%), and preoperative CT scan identified 2 of these. Twelve AcSs were located at the splenic hilum (75%). Nine patients experienced recurrence of their disease, and none had a missed AcS on subsequent scintigraphy. Sensitivity of exploratory laparoscopy for detection of AcS was 100%, and for preoperative CT scan was 12.5% (P = .005). CONCLUSION: Exploratory laparoscopy during splenectomy is more accurate than preoperative imaging with CT scan for detection of AcS. Preoperative CT scan misses AcS frequently and should not be obtained for the purpose of its identification.