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Melanoma: HELP
Articles by Stanley P. L. Leong
Based on 51 articles published since 2008

Between 2008 and 2019, Stanley Leong wrote the following 51 articles about Melanoma.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial How to reduce the incidence of neuropathic pain: sentinel node biopsy for diagnosis of metastatic malignant melanoma. 2011

Rowbotham, Michael C / Leong, Stanley P L. · ·Pain · Pubmed #21983239.

ABSTRACT: -- No abstract --

2 Review Cancer initiation and progression within the cancer microenvironment. 2018

Leong, Stanley P / Aktipis, Athena / Maley, Carlo. ·Department of Surgery and Melanoma Center, California Pacific Medical Center and Research Institute, San Francisco, USA. LeongSX@cpmcri.org. · Arizona Cancer and Evolution Center, Biodesign Institute, Arizona State University, Tempe, USA. ·Clin Exp Metastasis · Pubmed #29992410.

ABSTRACT: Within the cancer microenvironment, the growth and proliferation of cancer cells in the primary site as well as in the metastatic site represent a global biological phenomenon. To understand the growth, proliferation and progression of cancer either by local expansion and/or metastasis, it is important to understand the cancer microenvironment and host response to cancer growth. Melanoma is an excellent model to study the interaction of cancer initiation and growth in relationship to its microenvironment. Social evolution with cooperative cellular groups within an organism is what gives rise to multicellularity in the first place. Cancer cells evolve to exploit their cellular environment. The foundations of multicellular cooperation break down in cancer because those cells that misbehave have an evolutionary advantage over their normally behaving neighbors. It is important to classify evolutionary and ecological aspects of cancer growth, thus, data for cancer growth and outcomes need to be collected to define these parameters so that accurate predictions of how cancer cells may proliferate and metastasize can be developed.

3 Review Micrometastatic cancer cells in lymph nodes, bone marrow, and blood: Clinical significance and biologic implications. 2014

Leong, Stanley P L / Tseng, William W. ·Chief of Cutaneous Oncology, Associate Director of the Melanoma Program, Center for Melanoma Research and Treatment, California Pacific Medical Center and Sutter Pacific Medical Foundation, Senior Scientist, California Pacific Medical Center Research Institute, San Francisco, CA. ·CA Cancer J Clin · Pubmed #24500995.

ABSTRACT: Cancer metastasis may be regarded as a progressive process from its inception in the primary tumor microenvironment to distant sites by way of the lymphovascular system. Although this type of tumor dissemination often occurs in an orderly fashion via the sentinel lymph node (SLN), acting as a possible gateway to the regional lymph nodes, bone marrow, and peripheral blood and ultimately to distant metastatic sites, this is not a general rule as tumor cells may enter the blood and spread to distant sites, bypassing the SLN. Methods of detecting micrometastatic cancer cells in the SLN, bone marrow, and peripheral blood of patients have been established. Patients with cancer cells in their SLN, bone marrow, or peripheral blood have worse clinical outcomes than patients with no evidence of spread to these compartments. The presence of these cells also has important biologic implications for disease progression and the clinician's understanding of the process of cancer metastasis. Further characterization of these micrometastatic cancer cells at each stage and site of metastasis is needed to design novel selective therapies for a more "personalized" treatment.

4 Review Persistent postoperative pain and sensory changes following lymph node excision in melanoma patients: a topical review. 2014

Slagelse, Charlotte / Petersen, Karin L / Dahl, Jørgen B / Finnerup, Kenneth / Greene, Kaitlin / Leong, Stanley P / Levine, Jon / Rowbotham, Michael / Werner, Mads U / Finnerup, Nanna B. ·aCalifornia Pacific Medical Center Research Institute bDepartment of Medicine, Division of Rheumatology, University of California at San Francisco, San Francisco, California, USA cDepartment of Anaesthesia, Rigshospitalet and Copenhagen University dMultidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen eDanish Pain Research Center, Aarhus University, Aarhus fDepartment of Plastic Surgery, Aalborg University Hospital, Aalborg, Denmark. ·Melanoma Res · Pubmed #24346167.

ABSTRACT: Studies on complications related to chronic nerve injury following sentinel lymph node biopsy (SLNB) and complete lymph node dissection (CLND) for melanoma are sparse. This review summarizes the existing literature on pain and neuropathic complications in melanoma patients undergoing SLNB with or without CLND. The Cochrane Central Register of Controlled Trials and the Embase and PubMed databases were searched. Full-text English language articles published before June 2013 were included. Prospective and retrospective studies assessing persistent (>1 month) sensory nerve injury, postoperative pain, neuropathic pain, and sensory disturbances following SLNB with or without CLND in melanoma patients were eligible. Nine studies (six prospective and three retrospective) including data for 3632 patients met our inclusion criteria. Outcome parameters were too heterogeneous to conduct a quantitative analysis, and few studies systematically evaluated pain and sensory abnormalities. Persistent postoperative pain was reported in 1-14% of patients following SLNB and in 6-34% following CLND and sensory abnormalities in 0.1-32 and 2-82%, respectively. In the one study that assessed the type of pain, neuropathic pain was suggested to explain persistent pain in 31-66% of patients with SLNB and 82-89% of patients with CLND. Sensory-nerve-related complications in melanoma patients seem to be less pronounced following SLNB compared with CLND. Prospective observational studies are necessary to identify predictors of persistent pain, to evaluate the prevalence and impact of pain and sensory abnormalities, and to develop strategies for prevention of long-term complications.

5 Review Progression of cutaneous melanoma: implications for treatment. 2012

Leong, Stanley P L / Mihm, Martin C / Murphy, George F / Hoon, Dave S B / Kashani-Sabet, Mohammed / Agarwala, Sanjiv S / Zager, Jonathan S / Hauschild, Axel / Sondak, Vernon K / Guild, Valerie / Kirkwood, John M. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. leongsx@cpmcri.org ·Clin Exp Metastasis · Pubmed #22892755.

ABSTRACT: The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials.

6 Review Role of selective sentinel lymph node dissection in head and neck melanoma. 2011

Leong, Stanley P L. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center and Research Institute, San Francisco, California, USA. leongsx@cpmcri.org ·J Surg Oncol · Pubmed #21858830.

ABSTRACT: Selective sentinel lymph node dissection (SLND) plays an important role in the staging of the regional nodal basins for head and neck (H&N) melanoma. Preoperative lymphoscintigraphy is mandatory to identify the regional nodal basin(s) accurately for a newly diagnosed H&N primary melanoma of at least 1mm or greater. A wide local excision should be delayed if SLN mapping is indicated, to minimize watershed effect and maximize accuracy in identifying the "true" SLN because of the complex lymphatic network in the H&N region. An experienced multidisciplinary team is required for optimal identification of H&N SLNs. In general, selective SLND can replace ELND to minimize the complications of a neck dissection. Completion lymph node dissection is only indicated when the SLN is positive. A nerve stimulator should be used during selective SLND in the parotid and posterior triangle to minimize the injury to the facial and spinal accessory nerve.

7 Review Unique patterns of metastases in common and rare types of malignancy. 2011

Leong, Stanley P L / Nakakura, Eric K / Pollock, Raphael / Choti, Michael A / Morton, Donald L / Henner, W David / Lal, Anita / Pillai, Raji / Clark, Orlo H / Cady, Blake. ·Center for Melanoma Research and Treatmnet and Department of Surgery, California Pacific Medical Center and Research Institute, San Francisco, California 94115, USA. leongSX@cpmcri.org ·J Surg Oncol · Pubmed #21480255.

ABSTRACT: This review on the unique patterns of metastases by common and rare types of cancer addresses regional lymphatic metastases but also demonstrates general principles by consideration of vital organ metastases. These general features of successfully treated metastases are relationships to basic biological behavior as illustrated by disease-free interval, organ-specific behavior, oligo-metastatic presentation, genetic control of the metastatic pattern, careful selection of patients for surgical resection, and the necessity of complete resection of the few patients eligible for long-term survival after resection of vital organ metastasis. Lymph node metastases, while illustrating these general features, are not related to overall survival because lymph node metastases themselves do not destroy a vital organ function, and therefore have no causal relationship to overall survival. When a cancer cell spreads to a regional lymph node, does it also simultaneously spread to the systemic site or sites? Alternatively, does the cancer spread to the regional lymph node first and then it subsequently spreads to the distant site(s) after an incubation period of growth in the lymph node? Of course, if the cancer is in its incubation stage in the lymph node, then removal of the lymph node in the majority of cases with cancer cells may be curative. The data from the sentinel lymph node era, particularly in melanoma and breast cancer, is consistent with the spectrum theory of cancer progression to the sentinel lymph node in the majority of cases prior to distant metastasis. Perhaps, different subsets of cancer may be better defined with relevant biomarkers so that mechanisms of metastasis can be more accurately defined on a molecular and genomic level.

8 Review Cutaneous melanoma: a model to study cancer metastasis. 2011

Leong, Stanley P L / Gershenwald, Jeffrey E / Soong, Seng-Jaw / Schadendorf, Dirk / Tarhini, Ahmad A / Agarwala, Sanjiv / Hauschild, Axel / Soon, Christopher W M / Daud, Adil / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center and Research Institute, San Francisco, California 94115, USA. leongsx@cpmcri.org ·J Surg Oncol · Pubmed #21480247.

ABSTRACT: Nodal status in melanoma is a critically important prognostic factor for patient outcome. The survival rate drops to <10% when melanoma has spread beyond the regional lymph nodes and includes visceral involvement. In general, the process of melanoma metastasis is progressive in that dissemination of melanoma from the primary site to the regional lymph nodes occurs prior to systemic disease. The goal of this review article is to describe melanoma as a clinical model to study cancer metastasis. A future challenge is to develop a molecular taxonomy to subgroup melanoma patients at various stages of tumor progression for more accurate targeted treatment.

9 Review Implementing sentinel lymph node biopsy programs in developing countries: challenges and opportunities. 2011

Keshtgar, Mohammed / Zaknun, John J / Sabih, Durre / Lago, Graciela / Cox, Charles E / Leong, Stanley P L / Mariani, Giuliano. ·University Department of Surgery, Royal Free and University College London Medical School, London, UK. ·World J Surg · Pubmed #21267566.

ABSTRACT: BACKGROUND: Sentinel lymph node biopsy (SLNB) is the accepted standard of care in early-stage breast cancer and cutaneous melanoma. This technology is accurate for nodal staging and determining the prognosis of these patients. There are several randomized controlled trials confirming the accuracy of this technique and confirming its role in reducing morbidity and improving quality of life. It is also gaining increased acceptance in the management of other solid tumors. Despite the established benefits of SLNB as a minimally invasive approach for nodal staging, the procedure is still underutilized in many developing countries. METHODS: The Human Health Division of the International Atomic Energy Agency (IAEA) convened advisory meetings with panels of multidisciplinary experts from different backgrounds with the remit to analyze the difficulties encountered by developing countries in establishing a successful SLNB program. The other remit of the panel was to recommend an effective program based on existing evidence that can be adapted and implemented in developing countries. The experience of some members of the panel in the training for this technique in Asia, Latin America, and Africa provided the insight required for the development of a comprehensive and structured program. The panel included recommendations on the technical aspects of the procedure, as well as a comprehensive training program, including theoretical teaching, practical training in surgical skills, laboratories, and hands-on proctored learning. Particular emphasis was placed on in-built quality assurance requirements to ensure that this powerful staging investigation is implemented with the highest possible standard in the management of cancer patients, with the lowest false negative rate. CONCLUSIONS: It is hoped that this article will be a useful resource for our colleagues planning to establish a SLNB program.

10 Review Patellar metastatic melanoma in a 13-year-old boy. 2010

Burk, Thomas F / Horvai, Andrew E / Gottschalk, Alexander R / Leong, Stanley P L / Kashani-Sabet, Mohammed / Goldsby, Robert E / Law, Jason / O'Donnell, Richard J. ·Department of Orthopaedic Surgery, University of California, San Francisco, USA. odonnelr@orthosurg.ucsf.edu ·Am J Orthop (Belle Mead NJ) · Pubmed #21720575.

ABSTRACT: The incidence of melanoma in US adults is approximately 1.5 per million, with 2% to 5% of patients developing metastatic disease. In children, melanoma is distinctly uncommon, and metastatic disease occurs even more seldom. This case report, the first of a patellar lesion as the initial presentation of metastatic melanoma in a pediatric patient, highlights use of patellectomy and intraoperative radiation therapy in obtaining palliative local control while avoiding periarticular functional morbidity.

11 Clinical Trial The safety of and indications for immediate reconstruction of head and neck melanoma defects: our early experience. 2014

Parrett, Brian M / Kashani-Sabet, Mohammed / Leong, Stanley P L / Buncke, Neal / Singer, Mark I. ·From the *Buncke Clinic, and †Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, CA. ·Ann Plast Surg · Pubmed #24691340.

ABSTRACT: Melanoma excision requires wide margins, leaving large defects. Surgical dogma has taught that definitive reconstruction of melanoma defects be performed after permanent pathology results, with skin grafts favored. However, this results in an open wound and the need for a second operation. The advantages of immediate reconstruction with flaps are single-stage surgery, high patient satisfaction, no period of disfigurement, and cost savings. Our purpose was to evaluate rate of positive margins and local recurrence after immediate reconstruction of head and neck melanoma (HNM) defects with flaps to determine safety of this approach. We prospectively followed all patients with HNM treated at a single center from January 2010 to June 2012 and collected patient and tumor data and reconstruction type. Outcomes assessed were permanent pathology margins and local recurrence rate. Risk factors for positive margins were assessed. Seventy-six patients with HNM were treated with wide excision and immediate flap reconstruction with a mean age of 59 years. Five patients had melanoma in situ and 71 had invasive melanoma. There was a 15.4% ulceration rate. Median thickness for invasive melanoma was 2.2 mm. Mean excision margin was 1.4 cm. Median follow-up was 2 years; 5.3% of patients had positive margins on permanent pathology after reconstruction and 3 were reexcised with negative margins. Local recurrence rate was 2.6% with no recurrence in patients with previous reexcised positive margins. Significant risk factors for positive margins were melanoma in situ excised with 5-mm margins (P=0.012) and desmoplastic melanoma (P<0.02). Immediate flap reconstruction after excision of HNM can be safely performed with low positive margin and local recurrence rates. This should be offered to patients, especially those with primary melanomas with distinct borders and excision margins greater than or equal to 1 cm.

12 Clinical Trial Combined analysis of phase III trials evaluating [⁹⁹mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. 2013

Sondak, Vernon K / King, Dennis W / Zager, Jonathan S / Schneebaum, Schlomo / Kim, Julian / Leong, Stanley P L / Faries, Mark B / Averbook, Bruce J / Martinez, Steve R / Puleo, Christopher A / Messina, Jane L / Christman, Lori / Wallace, Anne M. ·H. Lee Moffitt Cancer Center, Tampa, FL, USA. vernon.sondak@moffitt.org ·Ann Surg Oncol · Pubmed #23054107.

ABSTRACT: BACKGROUND: [(99m)Tc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [(99m)Tc]tilmanocept to vital blue dye. METHODS: Patients received [(99m)Tc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [(99m)Tc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials. RESULTS: Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [(99m)Tc]tilmanocept, for 98.7 % concordance (p < 0.001). [(99m)Tc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [(99m)Tc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [(99m)Tc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [(99m)Tc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [(99m)Tc]tilmanocept. No serious adverse events were attributed to [(99m)Tc]tilmanocept. CONCLUSIONS: [(99m)Tc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.

13 Clinical Trial A phase 2 study of (99m)Tc-tilmanocept in the detection of sentinel lymph nodes in melanoma and breast cancer. 2011

Leong, Stanley P L / Kim, Julian / Ross, Merrick / Faries, Mark / Scoggins, Charles R / Metz, Wendy L Rich / Cope, Frederick O / Orahood, Richard C. ·California Pacific Medical Center and Sutter Pacific Medical Foundation and Research Institute, University of California, San Francisco, CA, USA. leongsx@cpmcri.org ·Ann Surg Oncol · Pubmed #21331809.

ABSTRACT: BACKGROUND: Several (99m)Tc-labeled agents that are not approved by the U.S. Food and Drug Administration are used for lymphatic mapping. A new low-molecular-weight mannose receptor-based, reticuloendothelial cell-directed, (99m)Tc-labeled lymphatic imaging agent, (99m)Tc-tilmanocept, was used for lymphatic mapping of sentinel lymph nodes (SLNs) from patients with primary breast cancer or melanoma malignancies. This novel molecular species provides the basis for potentially enhanced SLN mapping reliability. METHODS: In a prospectively planned, open-label phase 2 clinical study, (99m)Tc-tilmanocept was injected into breast cancer and cutaneous melanoma patients before intraoperative lymphatic mapping. Injection technique, preoperative lymphoscintigraphy (LS), and intraoperative lymphatic mapping with a handheld gamma detection probe were performed by investigators per standard practice. RESULTS: Seventy-eight patients underwent (99m)Tc-tilmanocept injection and were evaluated (47 melanoma, 31 breast cancer). For those whom LS was performed (55 patients, 70.5%), a (99m)Tc-tilmanocept hot spot was identified in 94.5% of LS patients before surgery. Intraoperatively, (99m)Tc-tilmanocept identified at least one regional SLN in 75 (96.2%) of 78 patients: 46 (97.9%) of 47 in melanoma and 29 (93.5%) of 31 in breast cancer cases. Tissue specificity of (99m)Tc-tilmanocept for lymph nodes was 100%, displaying 95.1% mapping sensitivity by localizing in 173 of 182 nodes removed during surgery. The overall proportion of (99m)Tc-tilmanocept-identified nodes that contained metastatic disease was 13.7%. Five procedure-related serious adverse events occurred, none related to (99m)Tc-tilmanocept. CONCLUSIONS: Our results demonstrate the safety and efficacy of (99m)Tc-tilmanocept for use in intraoperative lymphatic mapping. The high intraoperative localization and lymph node specificity of (99m)Tc-tilmanocept and the identification of metastatic disease within the nodes suggest SLNs are effectively identified by this novel mannose receptor-targeted molecule.

14 Clinical Trial Immunotherapy with dendritic cells pulsed by autologous dactinomycin-induced melanoma apoptotic bodies for patients with malignant melanoma. 2009

Chang, John W C / Hsieh, Jia-Juan / Shen, Yung-Chi / Ho, E / Chuang, Cheng-Keng / Chen, Yu-Ray / Liao, Shuen-Kuei / Chen, Jen-Shi / Leong, Stanley P L / Hou, Ming-Mo / Chang, Nai-Jen / Wang, Cheng-Hsu. ·Division of Hematology-Oncology, Department of Internal Medicine, Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. wen1902@hotmail.com ·Melanoma Res · Pubmed #19750589.

ABSTRACT: The primary goal of this study was to evaluate the efficacy of immunotherapy for patients with metastatic melanoma with autologous melanoma apoptotic bodies (MAB)-pulsed dendritic cells (DCs). Accessible tumors from eligible patients with refractory metastatic melanoma were surgically removed and processed for primary culture. The autologous tumor cells were treated with dactinomycin to obtain MAB. To generate DCs, adherent peripheral blood mononuclear cells were cultured in complete medium containing granulocyte macrophage-colony stimulating factor and interleukin-4. MAB-pulsed DCs were given either intradermally (i.d.) or intravenously. Patients were immunized at monthly intervals and boosted with keyhole limpet hemocyanin (KLH) and MAB 2 weeks post-vaccination, with a maximum of four cycles. Of the 10 patients enrolled in this trial, nine were treated with MAB-pulsed DCs; two were given intravenous vaccinations and the other seven were i.d. injected. Mild tenderness in the draining lymph nodes lasting for less than 48 h and enlargement of the draining lymph nodes were noted in all seven i.d. cases. Treatment-related grade 3-4 toxicity, neutropenia, skin ulceration, tumor growth at the injection site, and sepsis were not observed in any of the patients. Delayed-type hypersensitivity to KLH was observed in all patients, whereas no delayed-type hypersensitivity to autologous tumor antigens was observed. One patient achieved partial response with reduction in lung metastatic tumor mass, and a presence of vesicles in the post-vaccination KLH response. Two patients had stable disease for more than 24 months; one was still alive at the time of submission of this report, the other eventually developed multiple metastases. MAB-pulsed DC immunotherapy is well tolerated in patients with malignant melanoma; however, its efficacy is only modest. Combination with other modalities is required to enhance DC-based immunotherapy.

15 Article Microsatellitosis in Patients with Melanoma. 2019

Karakousis, Giorgos C / Gimotty, Phyllis A / Leong, Stanley P / Pockaj, Barbara A / White, Richard L / O'Donoghue, Cristina / Sinnamon, Andrew J / Bartlett, Edmund K / Dueck, Amylou C / Gould Rothberg, Bonnie E / Messina, Jane L / Vetto, John T / Sondak, Vernon K / Schneebaum, Schlomo / Kashani-Sabet, Mohammed / Han, Dale / Faries, Mark B / Zager, Jonathan S / Anonymous2571200. ·Hospital of the University of Pennsylvania, Philadelphia, PA, USA. giorgos.karakousis@uphs.upenn.edu. · Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. · California Pacific Medical Center and Research Institute, San Francisco, CA, USA. · Mayo Clinic, Phoenix, AZ, USA. · Carolinas Medical Center, Charlotte, NC, USA. · Department of Surgery, Rush Medical College, Chicago, IL, USA. · Hospital of the University of Pennsylvania, Philadelphia, PA, USA. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Yale University School of Medicine, New Haven, CT, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Oregon Health and Science University, Portland, OR, USA. · Ichilov Hospital, Tel Aviv, Israel. · Angeles Clinic and Research Institute, Los Angeles, CA, USA. ·Ann Surg Oncol · Pubmed #30421045.

ABSTRACT: BACKGROUND: Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. METHODS: The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. RESULTS: The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4-93.3%), 54.1% (95% CI 45.4-59.7%), and 44.2% (95% CI 25.4-63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0-74.2%), while no significant difference was observed for the stage IIIC or D cohorts. CONCLUSIONS: SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.

16 Article The Intraoperative Portable Gamma Camera Is an Important Adjunct to the Gamma Probe in Identifying Melanoma Sentinel Lymph Nodes. 2018

Leong, Stanley P. ·California Pacific Medical Center and Research Institute, San Francisco, CA, USA. LeongSX@cpmcri.org. ·Ann Surg Oncol · Pubmed #30218245.


17 Article Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative Rate for Melanoma Sentinel Lymph Node Surgery. 2018

Leong, Stanley P / Wu, Max / Lu, Ying / Torre, Donald M / von Bakonyi, Anna / Ospina, Arianna M / Newsom, James D / Luckett, William S / Soon, Christopher W / Kim, Kevin B / Kashani-Sabet, Mohammed. ·California Pacific Medical Center, San Francisco, CA, USA. leongsx@cpmcri.org. · California Pacific Medical Center, San Francisco, CA, USA. · Stanford University, Stanford, CA, USA. ·Ann Surg Oncol · Pubmed #30105436.

ABSTRACT: BACKGROUND: Preoperative imaging and intraoperative gamma probe (GP) localization is standard for identifying sentinel lymph nodes (SLNs) in melanoma patients. The aim of this prospective Institutional Review Board-approved study was to investigate whether an intraoperative portable gamma camera (PGC) improves SLN detection over the GP. METHODS: Lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed after injection of 99mTc-Tilmanocept in melanoma patients (≥ 18 years, Breslow thickness ≥ 1.0 mm). A GP was used to localize the SLNs in each basin, which was explored by the GP to ensure that the operative field was < 10% counts of the hottest SLN. The PGC was then used after a negative GP screening. Any residual hotspots identified by the PGC were considered as additional SLNs and were removed following the 10% rule. RESULTS: Preoperative imaging of 100 patients identified 138 SLN basins, with 306 SLNs being identified by conventional surgery. The PGC localized 89 additional SLNs in 54 patients. Thus, the PGC identified an additional 23% of SLNs [95% confidence interval (CI) 18-27%]. Four of these 89 SLNs showed micrometastasis in four patients, in two of whom the only tumor-positive SLN was identified by the PGC, preventing two false-negative cases. Thus, the null hypothesis that the PGC did not detect additional positive SLNs was rejected (p = 0.000). The overall SLN positive rate was 9.9% (39/395, 95% CI 6-12), and the overall patient positive rate was increased using the PGC, from 25 to 27% (27/100). CONCLUSIONS: Intraoperative PGC imaging yielded additional SLNs in a significant number of patients over GP alone. Identification of these additional SLNs resulted in upstaging of four patients with two patients being converted from a negative to a positive status, thus, preventing two false-negative cases.

18 Article Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies. 2018

Vosoughi, Elham / Lee, Jee Min / Miller, James R / Nosrati, Mehdi / Minor, David R / Abendroth, Roy / Lee, John W / Andrews, Brian T / Leng, Lewis Z / Wu, Max / Leong, Stanley P / Kashani-Sabet, Mohammed / Kim, Kevin B. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 2100 Webster Street, Suite 326, San Francisco, CA, 94115, USA. · Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, 2100 Webster Street, Suite 326, San Francisco, CA, 94115, USA. KimKB@sutterhealth.org. ·BMC Cancer · Pubmed #29703161.

ABSTRACT: BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. RESULTS: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. CONCLUSIONS: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

19 Article Stratifying SLN incidence in intermediate thickness melanoma patients. 2018

Chang, James M / Kosiorek, Heidi E / Dueck, Amylou C / Leong, Stanley P L / Vetto, John T / White, Richard L / Avisar, Eli / Sondak, Vernon K / Messina, Jane L / Zager, Jonathan S / Garberoglio, Carlos / Kashani-Sabet, Mohammed / Pockaj, Barbara A. ·Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA. · Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA. · Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. · Department of Surgery, Oregon Health & Science University, Portland, OR, USA. · Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA. · Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. · Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA. · Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA. · Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA. Electronic address: pockaj.barbara@mayo.edu. ·Am J Surg · Pubmed #29502857.

ABSTRACT: BACKGROUND: Guidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for positive SLNB. METHODS: A retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01-4.00 mm) who had SLNB, and assessed predictors for positive SLNB. RESULTS: 3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm CONCLUSIONS: Intermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.

20 Article Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690. 2017

Kashani-Sabet, Mohammed / Nosrati, Mehdi / Miller, James R / Sagebiel, Richard W / Leong, Stanley P L / Lesniak, Andrew / Tong, Schuyler / Lee, Sandra J / Kirkwood, John M. ·Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California. kashani@cpmcri.org. · Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California. · Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania. · Dana-Farber Cancer Institute, Boston, Massachusetts. · ECOG-ACRIN Melanoma Committee, Philadelphia, Pennsylvania. · University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. ·Clin Cancer Res · Pubmed #28790109.


21 Article Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin? 2017

Rios-Cantu, Andrei / Lu, Ying / Melendez-Elizondo, Victor / Chen, Michael / Gutierrez-Range, Alejandra / Fadaki, Niloofar / Thummala, Suresh / West-Coffee, Carla / Cleaver, James / Kashani-Sabet, Mohammed / Leong, Stanley P L. ·Center for Melanoma Research & Treatment, California Pacific Medical Center, 2340 Clay Street, 2nd Floor, San Francisco, CA, 94115, USA. · Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico. · Consorcio de Universidades Mexicanas (CuMEX), Pachuca, Mexico. · Departments of Biomedical Data Science, Health Research and Policy, and Radiology, The Stanford Cancer Institute, Stanford University, Stanford, CA, USA. · University of Nevada, Las Vegas, Las Vegas, NV, USA. · Department of Dermatology, University of California, San Francisco, CA, USA. · Center for Melanoma Research & Treatment, California Pacific Medical Center, 2340 Clay Street, 2nd Floor, San Francisco, CA, 94115, USA. leongsx@cpmcri.org. ·Clin Exp Metastasis · Pubmed #28699042.

ABSTRACT: Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8-26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4-15+ years) and 1.2 years with positive CLND (95% CI 1.0-1.8 years). The 5-year overall survival rates were 67% (95% CI 61-74%) for negative CLND versus 38% (95% CI 28-52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3-15+ years) and 2.5 years for positive CLND (95% CI 2.2-5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non-SLN compartment and beyond to the systemic sites.

22 Article Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas? 2017

Schuitevoerder, Darryl / Leong, Stanley P L / Zager, Jonathan S / White, Richard L / Avisar, Eli / Kosiorek, Heidi / Dueck, Amylou / Fortino, Jeanine / Kashani-Sabet, Mohammed / Hart, Kyle / Vetto, John T. ·Department of Surgery, Oregon Health & Science University, Portland, OR, USA. Electronic address: schuitev@ohsu.edu. · Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. · Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA. · Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA. · Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA. · Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA. · Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland, OR, USA. · Department of Surgery, Oregon Health & Science University, Portland, OR, USA. ·Am J Surg · Pubmed #28411863.

ABSTRACT: 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.

23 Article Selective Sentinel Lymph Node Dissection in Lower Extremity Melanoma. 2016

Miranda, Suzette G / Parrett, Brian M / Li, Rui Rachel / Lee, Grant / Chang, Tiffany / Fadaki, Niloofar / Cardona-Huerta, Servando / Cleaver, James E / Kashani-Sabet, Mohammed / Leong, Stanley P. ·San Francisco, Calif. From The Buncke Clinic, California Pacific Medical Center; the Departments of Surgery and Dermatology, University of California, San Francisco; Medivation Biostatistics; and the Center for Melanoma Research & Treatment, California Pacific Medical Center & Research Institute. ·Plast Reconstr Surg · Pubmed #26809037.

ABSTRACT: BACKGROUND: There is debate as to whether deep inguinal lymph nodes should be removed with the superficial or femoral lymph nodes during sentinel lymph node biopsy for lower extremity melanoma, when both superficial and deep inguinal lymph nodes are identified by preoperative lymphoscintigraphy. This study evaluated the lymphatic drainage patterns in lower extremity melanoma to determine whether certain patterns could be used to limit the level of node removal and define the extent of dissection. METHODS: A retrospective outcomes review was performed of lower extremity melanoma patients with excision and sentinel lymph node biopsy from 1995 to 2010. Outcomes included location of sentinel lymph node drainage basins, sentinel lymph node-positivity, and disease-free and overall survival, with drainage patterns compared between above- and below-knee melanomas. RESULTS: Of 499 patients with lower extremity melanoma having sentinel lymph node biopsy, 356 had below-the-knee and 143 had above-the-knee melanoma. For below-knee melanoma, the node-positivity rate was 23 percent (63 of 271) for superficial inguinal, 0 percent (zero of three) for deep inguinal, and 50 percent (one of two) for popliteal basins. For above-knee melanoma, the positivity rate was 21 percent (24 of 113) for superficial inguinal, 33 percent (one of three) for deep inguinal basins, and 0 percent (zero of zero) for popliteal basins. Importantly, no patients with a negative superficial inguinal sentinel lymph node had a positive deep inguinal sentinel lymph node on final pathologic evaluation [corrected]. CONCLUSIONS: A difference was noted in patterns of sentinel lymph node drainage from lower extremity melanoma below and above the knee. Biopsy for deep inguinal basins may be deferred if there is simultaneous drainage to the superficial inguinal basin by preoperative lymphoscintigraphy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

24 Article The role of BPTF in melanoma progression and in response to BRAF-targeted therapy. 2015

Dar, Altaf A / Nosrati, Mehdi / Bezrookove, Vladimir / de Semir, David / Majid, Shahana / Thummala, Suresh / Sun, Vera / Tong, Schuyler / Leong, Stanley P L / Minor, David / Billings, Paul R / Soroceanu, Liliana / Debs, Robert / Miller, James R / Sagebiel, Richard W / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment (AAD, MN, VB, DdS, ST, VS, ST, SPLL, DM, JRMIII, RWS, MKS), California Pacific Medical Center Research Institute, San Francisco, CA (AAD, MN, VB, DdS, ST, VS, ST, SPLL, DM, LS, RD, JRMIII, RWS, MKS) · Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, CA (SM) · Life Technologies, Inc. Carlsbad, CA (PRB). ·J Natl Cancer Inst · Pubmed #25713167.

ABSTRACT: BACKGROUND: Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma. METHODS: The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided. RESULTS: shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents. CONCLUSIONS: These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF.

25 Article Targeting ALDH1 to decrease tumorigenicity, growth and metastasis of human melanoma. 2015

Yue, Lili / Huang, Zhi-Ming / Fong, Stephen / Leong, Stanley / Jakowatz, James G / Charruyer-Reinwald, Alex / Wei, Maria / Ghadially, Ruby. ·Departments of aDermatology bSurgery, University California at San Francisco cDepartment of Dermatology, Veterans Affairs Medical Center, San Francisco dDepartment of Surgery, University California at Irvine, Irvine, California, USA. ·Melanoma Res · Pubmed #25643237.

ABSTRACT: Cells with aldehyde dehydrogenase activity (ALDH+) are the most tumorigenic cells in many cancers, including melanoma, making ALDH a candidate therapeutic target. We examined the effects of chemical inhibition of ALDH1 on the response of human melanoma xenografts to chemotherapy and the effects of ALDH1A1 RNA silencing on melanoma growth and metastasis. Addition of ALDH1 inhibitors (e.g. diethylaminobenzaldehyde) to dacarbazine chemotherapy, not only reduced tumor growth in vivo, but also resulted in a significant decrease in the number of residual cells capable of tumorigenesis. shRNA depletion of ALDH1A1 in melanoma cells resulted not only in a significant delay in appearance of xenograft melanomas and reduction in growth, but also significantly decreased the number of metastases and metastatic burden after lateral tail vein injections in mice. In summary, ALDH1 inhibition in combinatorial therapy with dacarbazine reduced the number of residual tumorigenic cells post-therapy and ALDH1A1 depletion had marked inhibitory effects on both melanoma growth and metastasis. These findings suggest that ALDH1 inhibition may not only be able to provide a therapeutic advantage in melanoma treatment, but may also prevent rapid relapse after therapy, as residual tumorigenic cells are fewer and metastatic ability is diminished.