Melanoma Of Esophagus Research Articles

A Rare and Rapidly Progressive Case of Primary Esophageal Malignant Melanoma in an Elderly Patient

A Rare and Rapidly Progressive Case of Primary Esophageal Malignant Melanoma in an Elderly Patient

Genomic landscape of cutaneous, acral, mucosal, and uveal melanoma in Japan: analysis of clinical comprehensive genomic profiling data.

Cutaneous melanoma (CM) is the most common type in Caucasians, while acral melanoma (AM) and mucosal melanoma (MM), which are resistant to immunotherapies and BRAF/MEK-targeted therapies, are more common in East Asians. Genomic profiling is essential for treating melanomas, but such data are lacking in Japan. Comprehensive genomic profiling data compiled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were analyzed. A total of 380 melanomas was analyzed, including 136 CM, 46 AM, 168 MM, and 30 uveal melanoma (UM). MM included conjunctival, sinonasal, oral, esophageal, anorectal, and vulvovaginal melanomas. No significant difference in the median tumor mutational burden (TMB) of CM (3.39 mutations/megabase), AM (2.76), and MM (3.78) was the key finding. Microsatellite instability-high status was found in one case. BRAF V600E/K was found in only 45 patients (12%). Key driver mutations in CM were BRAF (38%), NRAS (21%), NF1 (8%), and KIT (10%), with frequent copy number alterations (CNAs) of CDKN2A, CDKN2B, and MYC. AM was characterized by altered KIT (30%), NRAS (26%), and NF1 (11%) and CDKN2A, CDKN2B, CDK4, MDM2, and CCND1 CNAs. MM was characterized by altered NRAS (24%), KIT (21%), and NF1 (17%) and MYC, KIT, and CDKN2A CNAs, with differences based on anatomical locations. UM bore GNAQ or GNA11 driver mutations (87%) and frequent mutations in SF3B1 or BAP1. The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.

MUC21: a new target for tumor treatment.

MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a transmembrane domain and a cytoplasmic tail. MUC21 is expressed is observed in normal tissues in organs like the thymus, testes, lungs, and large intestine. Research has shown that MUC21 is expressed in esophageal squamous cell carcinoma, lung adenocarcinoma, glioblastoma, thyroid cancer, melanoma, and various other malignant tumors in distinctive manner. Additionally, tumor invasion, metastasis, and poor prognosis are linked to it. Some researchers believe that MUC21 has the potential to become a new target in cancer treatment. This review aims to deliver a comprehensive overview of the glycosylation, function, and research progress of MUC21 in multiple types of cancer and infectious diseases.

Comprehensive analysis of TMB, TNB, and HLA via NGS sequencing in a large cohort of Chinese pan-cancer patients.

2656 Background: Evidence suggests that patients with high tumor mutational burden (TMB) and tumor neoantigen burden (TNB) are more likely to benefit from Immune checkpoint inhibitors (ICIs). Furthermore, loss of heterozygosity (LOH) in human leukocyte antigen (HLA) alleles, particularly HLA class I, impairs neoantigen presentation and contributes to resistance against ICIs. This study provides real-world insights into the distribution of TMB, TNB, and HLA variations within a large cohort of Chinese patients with various cancers. Methods: From 2021 to 2023, we performed a retrospective analysis on 1603 cancer patients, examining genetic mutations and HLA traits using the Med1 CDx DNA-based NGS panel targeting 601 cancer-related genes and HLA class I. TMB was calculated as the average number of coding mutations per megabase of the genome. HLA class I alleles (HLA-A, B and C) were identified and predicted using the OptiType and pVACtools software suites. TNB was defined as the number of high-affinity (IC50 ≤ 50 nM) neoantigens per megabase of the genome. Statistical analyses were performed to explore the relationship between TMB, TNB, and LOH status in critical regions of HLA. Results: This study enrolled participants across 25 cancer types. With 32.56% having non-small cell lung cancer (NSCLC), 11.79% colorectal carcinoma (CRC), and 18.34% unidentified solid tumors. The remaining 37.31% comprised cases of cholangiocarcinoma, hepatocellular carcinoma, pancreatic cancer, etc. High-affinity neoantigen-generating genes such as TP53, EGFR, KRAS, LRP1B, DMD, and FAT1 were identified. Our findings indicate substantial variation in tumor neoantigen burden (TNB) across various cancer types and even among different samples within the same type. Neuroendocrine tumors exhibited the highest TNB at 4 neoantigens/Mb, followed by esophageal cancer (3.3), melanoma and urothelial carcinoma (2.67 each), indicating higher TNB levels in these cancers compared to others. A significant positive correlation was observed between TMB and TNB (p< 0.0001). Analysis revealed no significant TNB differences attributable to age (cutoff at 60 years) or gender. However, individuals aged over 70 years demonstrated a higher TNB of 4 compared to those under 70 with 3.33, highlighting potential age-related differences in TNB. Conclusions: Our analysis highlights significant variation in TNB across cancer types, with the highest TNB found in neuroendocrine tumors and the lowest in gastrointestinal stromal tumors, indicating TNB's value as a biomarker for optimizing ICI therapy. Furthermore, we found that people over 70 years old have higher TNB levels than younger individuals, suggesting a potential for improved ICI efficacy without chemotherapy. The evident strong correlation between Tumor Mutational Burden (TMB) and TNB underlines their crucial role in the success of cancer immunotherapy.

Endoscopic semiotics and pathological characteristics of primary malignant esophageal melanoma: a case report

Primary malignant melanoma of the esophagus is defined as a tumor, the frequency of which is 0.1-0.2% of all malignant lesions of the esophagus. This type of neoplasia is difficult to diagnose and is characterized by rapid progression, high recurrence rate and metastasis. Despite the diagnostic capabilities of X-ray examination methods, which make it possible to identify a tumor and determine its localization, the correct diagnosis can only be established by endoscopic examination of the upper digestive tract with biopsy and subsequent pathological and immunohistochemical studies. A 78 year-old male patient was admitted to the Herzen Moscow State Medical Institute with suspected esophageal cancer. It is known from the anamnesis, that the patient for 6 months notes a dysphagia, pain in the chest area. Based on the data of our expert endoscopic examination, we suspected primary esophageal melanoma with a mixed growth - exophytic and flat-type. According to the results of pathological examination of the biopsies, pigment epithelial-cell melanoma of the esophagus with high mitotic index (up to 3 mitosis figures per 1 sq.mm) with infiltrative growth type. This clinical case demonstrates the importance of a detailed endoscopic examination and performing a targeted biopsy, followed by expert pathological examination in the differential diagnosis of esophageal diseases characterized by pigmentation of mucosa.

Esophageal Melanoma - A Rare Neoplasm

A 70 year old man having progressive dysphagia, coronary artery disease (CAD) with an Ejection Fraction (EF) of 30% was detected to have a poorly differentiated esophageal malignancy. Immunohistochemistry (IHC) was positive for HMB 45 and SOX 10 confirming esophageal melanoma. In view of advanced age and poor cardiac function, surgical treatment was not feasible. Palliative esophageal metallic stenting was performed. Immunotherapy was suggested with ICI. We present this case in view of rarity of esophageal melanoma and to stress the need for evaluation with IHC in subjects with poorly differentiated esophageal malignancy.

Biological Potential and Therapeutic Effectiveness of Hinokiflavone in Medicine: The Effective Components of Herbal Medicines for Treatment of Cancers and Associated Complications

Background: Plants have been providing us medicines and food material for centuries. Traditional system of medicine, including Ayurveda, and Traditional Chinese medicines have been playing important role in health sectors for the treatment of human disorders since very early age. Plant secondary metabolites, including flavonoids, coumarins, saponins, and tannins have significant therapeutic potential in medicine. Biflavonoids are dimers of flavonoids, linked by a C–O–C or C–C bond. Hinokiflavone is an important class of biflavonoids found to be present in Toxicodendron succedaneum, Isophysis tasmanica, Juniperus rigida, Juniperus phoenicea, Platycladi cacumen, Rhus succedanea, Selaginella tamariscina, Platycladus orientalis, Selaginella bryopteris, and Metasequoia glyptostroboides. Methods: Biological potential of hinokiflavone in medicine have been analyzed in the present work through scientific data analysis of various literature work. Scientific database, including Google, Scopus, Science Direct, and PubMed were searched to collect all the scientific information of the present work using terms flavonoid, biflavonoid, herbal medicine, and hinokiflavone. Pharmacological activities of hinokiflavone were analyzed in the present work in very detailed manner. Analytical data of hinokiflavone were collected and analyzed in present work in order to know the biological source of hinokiflavone. Results: Present work signified the biological importance of hinokiflavone against various types of cancerous disorders, including breast cancer, colorectal cancer, esophageal squamous cancer, adenocarcinoma, hepatocellular carcinoma, myeloid leukemia, and melanoma. Further, its antiinflammatory, hepatoprotective, anti-viral, and anti-oxidant potential were also discussed in the present work. Moreover, its biological potential against COVID-19 and hair loss, and procoagulant activity were also summarized in this paper. Analytical data on hinokiflavone signified the importance of various analytical techniques in the extraction, separation, and identification of hinokiflavone with their pharmacokinetic parameters. Conclusion: Present work signified the biological importance and therapeutic potential of hinokiflavone in medicine.

Alcohol consumption and its association with cancer, cardiovascular, liver and brain diseases: a systematic review of Mendelian randomization studies.

The health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases. We searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool. We included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease. Despite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries. www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246154, Identifier: PROSPERO (CRD42021246154).

Primary esophageal melanoma with a family history of esophageal cancer

A rare clinical observation of a 46-year-old patient with primary esophageal melanoma is presented. We demonstrate the difficulties of verifying the disease, taking into account the complex morphological picture of the tumor, anatomical features. The possibilities of modern combined treatment of this category of patients are also shown. For the first time, a case of primary esophageal melanoma with a family history of esophageal cancer is described.

Bioactive C21 Steroidal Glycosides from Euphorbia kansui Promoted HepG2 Cell Apoptosis via the Degradation of ATP1A1 and Inhibited Macrophage Polarization under Co-Cultivation.

Euphorbia kansui is clinically used for the treatment of esophageal cancer, lung cancer, cancerous melanoma, asthma, pleural disorders, ascites, and pertussis, among other conditions. In this study, 12 steroids were obtained and identified from E. kansui, and cynsaccatol L (5), which showed the best effects in terms of inhibiting the proliferation of HepG2 cells and the immune regulation of macrophages. Furthermore, 5 induced typical apoptotic characteristics in HepG2 cells, such as morphological changes and the caspase cascade, as well as inducing autophagy-dependent apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. The antitumor mechanism of 5 might be related to promoting the endocytosis and degradation of ATP1A1 protein and then down-regulating the downstream AKT and ERK signaling pathways. Furthermore, the antiproliferation effect of 5 in co-cultivation with macrophages was investigated, which showed that 5 promoted the apoptosis of HepG2 cells by modulating the release of inflammatory cytokines, such as TNF-α and IFN-γ; regulating the M2-subtype polarization of macrophages; promoting the phagocytosis of macrophages. In conclusion, 5 exerted anti-proliferative effects by promoting the degradation of ATP1A1 and inhibiting the ATP1A1-AKT/ERK signaling pathway in HepG2. Furthermore, it regulated macrophage function in co-cultivation, thereby further exerting adjuvant anti-HepG2 activity.

An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers.

Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression. Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations. By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy. Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types. Swedish Cancer Society, Lions Cancer Foundation, Selanders Foundation, P.O. Zetterling Foundation, U-CAN supported by SRA CancerUU, Uppsala University and Region Uppsala.

Primary esophageal melanoma: features of diagnosis and treatment

Primary esophageal melanoma is a rare and extremely aggressive malignant neoplasm originating from mucosal melanocytes. The complex histological structure of the tumor, which in 10–25 % of cases may not contain melanin characteristic of these formations, leads to a high frequency of diagnostic errors, reaching 50 %. Immunohistochemical examination is the standard for diagnosing the disease. Primary esophageal melanoma is a tumor with a high potential for hematogenous and lymphogenous metastasis. So, when the tumor spreads to the submucosa, the frequency of locoregional metastasis reaches 54 %. Radical surgery in combination with adjuvant methods of treatment improves the results of treatment in this category of patients. Immunotherapy is a promising method of complex treatment, but requires further study.

Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Primary malignant melanoma of the esophagus successfully treated with camrelizumab: A case report and literature review*

Abstract An 83-year-old Chinese woman presented with a 3-month history of dysphagia. She also had a history of hypertension, type 2 diabetes, fundus hemorrhage, and cataract but no history of cutaneous, ocular, or other-site melanomas. Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum; thus, an endoscopic review was recommended. Enhanced computed tomography of the chest and upper abdomen revealed the following: (1) Esophageal space-occupying lesions and mediastinal lymph node enlargement (considering the high possibility of esophageal cancer, further endoscopy was recommended) and (2) A small amount of right pleural effusion, with no significant lymph node infiltration or distant metastasis. Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors. The upper mass had a spherical clustering, while the lower mass significantly festered. Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors. Tissue biopsy showed proliferation of large round tumor cells and melanocytes. Immunohistochemistry showed positive findings for HMB45 and MelanA; partially positive findings for S100, CK7, CK5/6, CAM5.2, LCA, P63, and TTF-1; and negative findings for Syn. The Ki-67 positivity index was approximately 60%. Based on these findings, the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes. She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18, 2019, to May 5, 2020. Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors, and there were two continuous uplifted and beaded masses that had a smooth and black surface, with each of them having a length and diameter of approximately 1 cm. Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia; the dentate margin was clear; and the cardia had no stenosis. The patient then received five courses of combination therapy and became consistently stable after partial remission. No severe adverse events related to the immunotherapy were recorded. Camrelizumab may be a viable treatment option for patients with PMME. Additional evidence from future clinical trials and research is necessary to fully validate our findings.

Immunotherapy of sarcomas with modified T cells.

To summarize the development of modified T-cell therapies in sarcomas and discuss relevant published and ongoing clinical trials to date. Numerous clinical trials are underway evaluating tumor-specific chimeric antigen receptor T cells and high affinity T-cell receptor (TCR)-transduced T cells in sarcomas. Notably, translocation-dependent synovial sarcoma and myxoid/round cell liposarcoma are the subject of several phase II trials evaluating TCRs targeting cancer testis antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen-A4 (MAGE A4), and response rates of up to 60% have been observed for NY-ESO-1 directed, modified T cells in synovial sarcoma. Challenges posed by modified T-cell therapy include limitations conferred by HLA-restriction, non-immunogenic tumor microenvironments (TME), aggressive lymphodepletion and immune-mediated toxicities restricting coinfusion of cytokines. Cellular therapy to augment the adaptive immune response through delivery of modified T cells is an area of novel therapeutic development in sarcomas where a reliably expressed, ubiquitous target antigen can be identified. Therapeutic tools to improve the specificity, signaling, proliferation and persistence of modified TCRs and augment clinical responses through safe manipulation of the sarcoma TME will be necessary to harness the full potential of this approach.

Clinicopathological Features, Staging Classification, and Clinical Outcomes of Esophageal Melanoma: Evaluation of a Pooled Case Series.

Studies that have attempted to validate the staging systems and the predictors of survival for patients with primary malignant melanoma of the esophagus (PMME) have been underpowered given their scarcity and small scale. We aimed to review a large number of PMME cases to know more about its clinicopathological features, TNM staging systems, and survival predictors of PMME. Case reports on PMME were extracted from PubMed/Medline through bibliography search and our center. A total of 287 PMME cases were identified. The majority of the patient population was male (72.08%). The most common location of PMME was the lower esophagus (50.62%) and middle esophagus (35.39%). Among the patients, 82.28% received surgical intervention. The median overall survival (OS) duration was 15 months (0.5–244). The American Joint Commission on Cancer staging classification (AJCC) for the mucosal melanoma of the upper aerodigestive tract with stage IVB and IVC integrated in stage IVA showed better distribution of OS than that for esophageal carcinoma. T stage, N stage, and surgery had significant impacts on OS duration in univariate analysis. However, only T stage and N stage were identified as independent factors for OS duration in the multivariate Cox models. PMME is an aggressive tumor with poor prognosis. The AJCC staging system for mucosal melanoma with stage IVB and IVC integrated in stage IVA may be a better option for staging PMME patients. T stage and N stage are independent factors for OS.

Clinicopathological assessment of cancer/testis antigens NY‑ESO‑1 and MAGE‑A4 in osteosarcoma.

The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers. Considering the limited information regarding their significance in osteosarcoma (OS), the purpose of this study was to determine the clinical significance of NY-ESO-1 and MAGE-A4 expression in OS. Nine patients with OS treated at Kindai University Hospital were included in the study. The median age was 27 years, and median follow-up period was 40 months. The specimens obtained at the time of biopsy were used to perform immunostaining for NY-ESO, MAGE-A4, p53, and Ki-67. The positive cell rates and positive case rates of NY-ESO, MAGE-A4, p53, and Ki-67 were calculated. The correlation between the positive cell rate of immunohistochemical markers was also calculated. The correlation between the positive cell rate of NY-ESO-1 or MAGE-A4 and tumor size or maximum standardized uptake (SUV-max) was also determined. The positive cell rates of NY-ESO-1 or MAGE-A4 in continuous disease-free (CDF) cases were also compared with those in alive with disease (AWD) or dead of disease (DOD) cases. The average positive cell rates of NY-ESO, MAGEA4, p53, and Ki-67 were 71.7%, 85.1%, 16.2%, and 14.7%, and their positive case rates were 33.3%, 100%, 44.4%, and 100%, respectively. The positivity rates of NY-ESO-1 and p53 were strongly correlated, whereas those of NY-ESO-1 and Ki-67 were moderately correlated. The MAGE-A4 and p53 positivity rates and the MAGE-A4 and Ki-67 positive cell rates were both strongly correlated. The NY-ESO-1 and MAGE-A4 positivity rates were moderately correlated. The positive correlation between the NY-ESO-1 positive cell rate and tumor size was medium, and that between the MAGE-A4 positivity rate and SUV-max was very strong. There was no significant difference in the positive cell rates of NY-ESO-1 or MAGE-A4 between CDF cases and AWD or DOD cases. Overall, our results suggest that NY-ESO-1 and MAGE-A4 may be involved in the aggressiveness of OS.

Phase 1 study of SGN-PDL1V, a novel, investigational vedotin antibody–drug conjugate directed to PD-L1, in patients with advanced solid tumors (SGNPDL1V-001, trial in progress).

TPS3154 Background: Programmed cell death ligand 1 (PD-L1) is a cell-surface protein involved in the programmed cell death protein 1 (PD-1)/PD-L1 immune checkpoint, which inhibits T-cell activation. Elevated PD-L1 expression is observed across a broad spectrum of solid tumor types. Expression of PD-L1 in tumors can signal through PD-1 on T cells to inhibit T-cell effector function. Blockade of the PD-1/PD-L1 signaling axis may restore antitumor immunity by reactivating T-cell effector function in the tumor microenvironment. SGN-PDL1V is a novel, investigational vedotin antibody–drug conjugate directed to PD-L1 with multiple proposed mechanisms of action including monomethyl auristatin E (MMAE)-directed cytotoxicity, bystander effect, and immunogenic cell death (ICD). Even in xenograft models with low, heterogeneous PD-L1 expression, SGN-PDL1V demonstrated antitumor activity via direct cytotoxicity and the bystander effect. Cytotoxicity mediated by SGN-PDL1V also led to immune activation due to MMAE-induced ICD (Kwan et al 2021). These preclinical findings provide a rationale for evaluating SGN-PDL1V in patients (pts) with advanced solid tumors. Methods: SGNPDL1V-001 (NCT05208762) is a phase 1, first-in-human, multicenter, open-label trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-PDL1V in pts with advanced solid tumors. This study includes 3 parts: dose escalation (Part A), dose and schedule optimization cohorts (Part B), and dose expansion in disease-specific cohorts and a biology cohort (Part C). Adult pts (≥18 years) with histologically/cytologically confirmed metastatic/unresectable solid tumors, including non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, melanoma, or ovarian cancer, will be eligible. Pts must have ECOG PS 0–1 and have failed or are unable to tolerate standard therapies. Pts must have PD-L1 expression ≥1 by tumor proportion score or combined positive score based on historical testing. Prior treatment with an MMAE-containing agent or an anti–PD-L1 agent (within 6 months) is not permitted. Primary endpoints include adverse events, laboratory abnormalities, dose-limiting toxicities, and cumulative dose-level safety. Secondary endpoints include rate and duration of objective response, progression-free survival, overall survival, PK, and incidence of antidrug antibodies. Exploratory endpoints include pharmacodynamics (PD), PK/PD relationships, and patient-reported outcomes. Safety and antitumor activity endpoints will be assessed using descriptive statistics. Objective response rate will be analyzed by tumor type, dose levels, and schedules. Enrollment for Part A is ongoing at sites in North America and is planned in Europe. Clinical trial information: NCT05208762.

Primary Esophageal Malignant Melanoma in Korea: Clinical features, Management and Prognosis.

Primary esophageal melanoma is a rare disease with a poor prognosis. To date, 18 cases have been reported in Korea. Four patients visited the Chonnam National University Hwasun Hospital with dysphagia, followed by epigastric pain and discomfort, odynophagia, and weight loss. Esophagogastroduodenoscopy revealed a black pigmented polypoid mass, protruding mass, or black-pigmented flat lesions. Two patients had distant metastases and lymphadenopathies in imaging studies. Two patients underwent esophagectomy and intrathoracic esophagogastrostomy. One patient was treated with chemotherapy and interferon-alpha. The other patient declined further treatment. The routine histology using H&E revealed brown-colored atypical melanocytes. Immunohistochemical staining exhibited strong reactivity for Melan-A, S-100, and HMB-45 proteins. The biopsy specimens were interpreted to be malignant melanoma. One patient had multiple distant metastases 13 months after surgery. The other patient had no recurrence for 33 months after surgery. The patient treated with chemotherapy and interferon-alpha showed disease progression in the follow-up examination. Primary esophageal melanoma in Korea is a rare disease characterized by aggressive behavior, early metastasis, and poor prognosis.

Clinical characteristics and treatment outcomes of primary malignant melanoma of esophagus: a single center experience

BackgroundPrimary malignant melanoma of esophagus (PMME) is an extremely rare disease with poor prognosis. We aimed to determine the clinical characteristics and treatment outcomes of patients with PMME.MethodsWe retrospectively reviewed 17 patients diagnosed with PMME in Samsung Medical Center between 2000 and 2020 with median 34 months of follow-up. Survival outcomes were analyzed with Kaplan–Meier method.Results15 patients (88.2%) were male and the most common presenting symptom was dysphagia (9/17, 52.9%). On endoscopy, tumors were mass-forming in 15 patients (88.2%) and diffusely infiltrative in two patients (11.8%). Lesions were melanotic in 13 patients (76.5%) and amelanotic in four patients (23.5%). The most common tumor location was lower esophagus (11/17, 64.7%). The disease was metastatic at the time of diagnosis in four patients (23.5%). As for treatment, 10 patients (58.8%) underwent surgery. In all 17 patients, the median overall survival was 10 months. In surgically treated patients, all patients experienced recurrence and the median disease-free survival was 4 months. There was no statistical difference in overall survival between patients with or without surgery. Patients with diffusely infiltrative tumor morphology had better overall survival compared to those with mass-forming tumor morphology (P = 0.048). Two patients who received immunotherapy as the first-line treatment without surgery showed overall survival of 34 and 18 months, respectively.ConclusionsAs radical resection for patients with PMME does not guarantee favorable treatment outcomes, novel treatment strategy is required. Further large-scale studies are warranted to determine the efficacy of immunotherapy for patients with PMME.