Melanoma Research Articles

Spinal Neurocutaneous Melanosis

Neurocutaneous melanosis is characterized by melanin-producing cells within the skin, leptomeninges, or brain parenchyma. It is a severe manifestation of congenital melanocytic nevus syndrome and can develop malignant melanomas. The disorder is commonly present in pediatric patients within the first two years of life and has a poor prognosis. We report a case of an 8-year-old male with epilepsy and cognitive deficit presenting spinal neurocutaneous melanosis.

Primary intracranial malignant melanomas: A case series with literature review.

There is a high chance of misdiagnosis and limited knowledge regarding therapeutic strategies owing to the rarity of primary intracranial malignant melanoma (PIMM). The objective of the present study was to evaluate the clinical features, treatment modalities, and outcomes of patients with histologically proven PIMM. Data of 15 patients with PIMM admitted to the Chinese People's Liberation Army General Hospital in a 14-year period between January 2005 and January 2019 were collected. Clinical presentations, pathology, surgical strategies, adjuvant treatment, and prognosis were retrospectively analyzed. CT showed iso- or high-density lesions in 12 cases (80%). MRI revealed short T1 and slightly short T2 in 14 cases (93.3%).The tumors showed mild or no enhancement on enhanced MRI. The patients were eventually diagnosed with PIMM through pathological examination. The treatment modalities included radical resection followed by conventional radiotherapy (RT, n = 12) and subtotal resection followed by stereotactic radiosurgery (n = 3). All 15 patients had either recurrence or metastasis at an average of 14.7 months (range, 6-23 months) after surgery. In total, 14 patients (93.3%) succumbed to disease, with a mean overall survival of 22 months (range, 6-36 months). The median survival time was 23 months. The overall survival rates at 1, 2, and 3 years were 80, 47, and 13%, respectively. Radical resection with RT was associated with longer overall survival (log-rank, P < .05) than subtotal resection followed by stereotactic radiosurgery. PIMM is an extremely rare tumor with a poor prognosis. Radical resection with RT may result in a longer overall survival rate. Targeted immunotherapy may be a promising treatment option for PIMM.

Impact on Survival with Immunotherapy and Evaluation of Biomarkers in Peruvian Patients with Advanced Melanoma.

Advanced malignant melanoma is a very aggressive disease, historically with poor prognosis before the new advances with immunotherapy and targeted therapies that have changed the standard of care, especially in cutaneous melanoma. Peru has aggressive features such as higher rates of acral lentiginous melanoma (ALM) subtype with historically shorter survival. This study describes Peruvian patients with advanced melanoma treated with immunotherapy (nivolumab) in two oncological institutions (public and private), including the discussion of the impact on overall survival (OS) divided by subtype (with incidence in ALM histology) and potential biomarkers that could be related to prognosis. We found that immunotherapy is safe, and improves progression-free survival (PFS), OS and objective response rate (ORR) in our patients, with lower benefit in ALM histology. No prognostic blood inflammatory biomarkers were detected. There is very limited data of Peruvian patients with metastatic melanoma treated with immunotherapy, especially the outcomes in ALM histology. Our goal is to share an example of the impact of immunotherapy in a Latin American (LATAM) population considered as an unsatisfied group with an enormous need of novel treatments and biomarkers.

Induced collagen type-I secretion by hepatocytes of the melanoma liver metastasis is associated with a reduction in tumour-infiltrating lymphocytes.

Overall patients with melanoma liver metastasis (MLiM) have a dismal prognosis and poor responses to the standard of care treatment. Understanding the role of the tumour microenvironment (TME) is critical for discovering better strategies to overcome intrinsic therapy resistance in MLiM. The aim was to understand the crosstalk signalling pathways between hepatocytes and metastatic melanoma cells in the TME of MLiM. Hepatocytes and melanoma tumour cells of MLiM were assessed using transcriptomic NanoString GeoMx digital spatial profiling (NGDSP) assay. Functional assays were performed using normal hepatocytes and MLiM-derived cell lines. Validation was performed using multiplex immunofluorescence. In NGDSP analysis adjacent normal hepatocytes (ANH) had higher CXCR4 and COL1A1/2 levels than distant normal hepatocytes (DNH), while melanoma cells had higher TNF-α levels. In vitro, MLiM cell lines released TNF-α which upregulated CXCR4 and CXCL12 levels in ANH. CXCL12 activated CXCR4, which triggered AKT and NFκB signalling pathways. Consequently, AKT signalling induced the upregulation of collagen type I. MLiM were significantly encircled by a shield of collagen, whereas other liver metastases showed reduced levels of collagen. Of all the liver metastasis analyzed, the presence of collagen in melanoma liver metastasis was associated with a reduction in tumour-infiltrating lymphocytes. MLiM modified ANH to increase collagen production and created a physical barrier. The collagen barrier was associated with a reduction of immune cell infiltration which could potentially deter MLiM immune surveillance and treatment responses. Spatial analyses of melanoma liver metastasis show that adjacent normal hepatocytes have increased collagen-type I levels. Melanoma liver metastases tumour cells secrete enhanced levels of TNF-α to stimulate CXCR4/CXCL12 upregulation in adjacent normal hepatocytes. Activation of CXCR4 promotes AKT and NF-κB signalling pathways to promote collagen-type I secretion in adjacent normal hepatocytes. Elevated collagen levels were associated with reduced tumour-infiltrating lymphocytes.

An Update on Access to Novel Treatment for Metastatic Melanoma in Europe — A 2024 Survey of the European Melanoma Registry and the European Association of Dermato-Oncology

An Update on Access to Novel Treatment for Metastatic Melanoma in Europe — A 2024 Survey of the European Melanoma Registry and the European Association of Dermato-Oncology

The first case of primary malignant melanoma of the esophagus to achieve pathologic complete response after preoperative ipilimumab + nivolumab followed by resection.

Primary malignant melanoma of the esophagus is a rare disease with a poor prognosis. Surgical resection is common, but there is no consensus on perioperative treatment. Studies have reported the efficacy of programmed cell death-1 inhibitors (e.g., nivolumab, pembrolizumab) and anti-cytotoxic T-lymphocyte-associated antigen 4 agents (e.g., ipilimumab) in treating malignant melanoma. Here, we present the first case of primary malignant melanoma of the esophagus with lymph node metastases treated with nivolumab and ipilimumab followed by resection, achieving a pathologic complete response. A 75-year-old man presented with dysphagia. Esophagogastroduodenoscopy revealed a black, elevated lesion in the mid-thoracic esophagus. Biopsy confirmed primary malignant melanoma of the esophagus, showing tumor cells with melanin deposition, positive for HBM45 and S-100 staining. Computed tomography showed enlarged lymph nodes in the subclavian and mediastinum regions, suggesting metastases. After two courses of preoperative chemotherapy with ipilimumab and nivolumab, which significantly shrank the tumor, the patient underwent robot-assisted subtotal esophagectomy and 3-field lymph node dissection. Histopathological examination revealed no tumors or lymph node metastases, confirming a pathologic complete response. Given the rarity and poor prognosis of primary malignant melanoma of the esophagus, this case provides valuable insights for treatment strategies.

Case report: Poor prognosis or poor prognostication?

This case highlights the limitations of current prognostication and communication in clinical practice. We report a case of a 50 year old patient with metastatic melanoma following admission to intensive care unit and later transferred to palliative care unit for end-of-life care. The patient had clinical improvement despite signs of predictors of death and was later transferred back to care of oncology team. Physicians frequently overestimate or underestimate survival time which can be distressing to patients and families. There is need for further research to improve the accuracy of these tools for the sake of our patients and their families.

Exploring resistance to immune checkpoint inhibitors and targeted therapies in melanoma.

Melanoma is the most aggressive form of skin cancer, characterized by a poor prognosis, and its incidence has risen rapidly over the past 30 years. Recent therapies, notably immunotherapy and targeted therapy, have significantly improved the outcome of patients with metastatic melanoma. Previously dismal five-year survival rates of below 5% have shifted to over 50% of patients surviving the five-year mark, marking a significant shift in the landscape of melanoma treatment and survival. Unfortunately, about 50% of patients either do not respond to therapy or experience early or late relapses following an initial response. The underlying mechanisms for primary and secondary resistance to targeted therapies or immunotherapy and relapse patterns remain not fully identified. However, several molecular pathways and genetic factors have been associated with melanoma resistance to these treatments. Understanding these mechanisms paves the way for creating novel treatments that can address resistance and ultimately enhance patient outcomes in melanoma. This review explores the mechanisms behind immunotherapy and targeted therapy resistance in melanoma patients. Additionally, it describes the treatment strategies to overcome resistance, which have improved patients' outcomes in clinical trials and practice.

Selective Clonal Regression After Interferon Therapy in Metastatic Melanoma.

Regression (total or partial) is a common phenomenon in melanoma. From a pathogenic perspective, it is highly complex and only partially understood, involving aspects of both the tumor and the individual. One of the determining factors is the clonal selection of the tumor, wherein some clones within the tumor survive while others perish. This clonal selection can sometimes occur as a selective mechanism after the initiation of a therapeutic intervention. In many of these cases, the effect is detrimental, because the surviving clone is resistant to the applied therapy. However, occasionally, the therapy can successfully select the less harmful clone. We present an example of the latter, where therapy with interferon induced regression of the metastatic-capable melanocytic population, with only the primary tumor melanocytic population persisting. To confirm this, we demonstrated BRAF mutational similarity between the 2 populations, and an additional NRAS mutation in the metastatic population, which was absent in the primary tumor.

E2F1-induced autocrine IL-6 inflammatory loop mediates cancer-immune crosstalk that predicts T cell phenotype switching and therapeutic responsiveness.

Melanoma is a metastatic, drug-refractory cancer with the ability to evade immunosurveillance. Cancer immune evasion involves interaction between tumor intrinsic properties and the microenvironment. The transcription factor E2F1 is a key driver of tumor evolution and metastasis. To explore E2F1's role in immune regulation in presence of aggressive melanoma cells, we established a coculture system and utilized transcriptome and cytokine arrays combined with bioinformatics and structural modeling. We identified an E2F1-dependent gene regulatory network with IL6 as a central hub. E2F1-induced IL-6 secretion unleashes an autocrine inflammatory feedback loop driving invasiveness and epithelial-to-mesenchymal transition. IL-6-activated STAT3 physically interacts with E2F1 and cooperatively enhances IL-6 expression by binding to an E2F1-STAT3-responsive promoter element. The E2F1-STAT3/IL-6 axis strongly modulates the immune niche and generates a crosstalk with CD4+ cells resulting in transcriptional changes of immunoregulatory genes in melanoma and immune cells that is indicative of an inflammatory and immunosuppressive environment. Clinical data from TCGA demonstrated that elevated E2F1, STAT3, and IL-6 correlate with infiltration of Th2, while simultaneously blocking Th1 in primary and metastatic melanomas. Strikingly, E2F1 depletion reduces the secretion of typical type-2 cytokines thereby launching a Th2-to-Th1 phenotype shift towards an antitumor immune response. The impact of activated E2F1-STAT3/IL-6 axis on melanoma-immune cell communication and its prognostic/therapeutic value was validated by mathematical modeling. This study addresses important molecular aspects of the tumor-associated microenvironment in modulating immune responses, and will contribute significantly to the improvement of future cancer therapies.

Response of Spontaneous Oral Tumors in Canine Cancer Patients Treated with Stereotactic Body Radiation Therapy (SBRT).

To describe outcome and toxicity for dogs with oral tumors, specifically oral malignant melanoma (OMM), squamous cell carcinoma (SCC), and soft tissue sarcoma (STS) after stereotactic body radiation therapy (SBRT). A single institution retrospective study was conducted. Outcomes were analyzed using Kaplan-Meier analysis and Cox proportional hazard analysis. Treatment responses at different time points were evaluated with Pearson's Chi-squared test to identify prognostic factors. Acute and late toxicities were recorded according to VRTOG criteria and were analyzed to identify risk factors. Adverse events other than acute and late toxicities were recorded. A total of 98 patients met the inclusion criteria (OMM n = 37; SCC n = 18; STS n = 43). The SBRT prescription was 1-6 fractions, with a total dose range of 12-40 Gy. Local progression-free survival (PFS) for OMM, SCC, and STS was 187, 253, and 161 days, respectively. Overall PFS was 152 days and median survival time (MST) was 270 days, with no statistical difference between tumor types. The presence of lymph node metastasis and the use of elective nodal irradiation (ENI) were associated with shorted PFS and MST. Severe acute toxicities to organs at risk affected 10/85 (11.8%) of patients. Osteoradionecrosis and oronasal fistula formation occurred in 23/81 (28.4%) of patients and was significantly associated with tumor type (SCC, P = 0.006). BRT can be offered as a treatment option for oral tumors in dogs. Toxicities were common and warrant risk factor considerations and adjustments to current SBRT protocols.

Does loss of CD44, low E-Cadherin and high Ki-67 expression in equine malignant melanoma have a relationship with biological behavior?

Los melanomas en equinos afectan todas las razas y aunque el 90% de estos tumores en esta especie son benignos, 66% de ellos progresan a formas malignas y pueden hacer metástasis, lo que se traduce en pérdidas económicas para propietarios. Por esta razón, es esencial la investigación de factores pronósticos y establecer su relación con criterios histopatológicos. El objetivo del trabajo fue identificar la expresión de CD44, E.cadherina y Ki67 y relacionarlos con hallazgos citológicos e histopatológicos en melanomas equinos con el fin de identificar una posible relación entre la expresión anatomo-clínica y el comportamiento biológico. Del archivo del laboratorio de patología de la Universidade Estadual Paulista “Júlio de Mesquita Filho”, Brasil, fueron seleccionados 15 casos de melanoma equino, confirmados por citología, histopatología (biopsia); las muestras fueron analizadas conforme criterios de atipia citológica, seguido de los criterios micrométricos de “Breslow”, subsecuentemente las muestras fueron sometidas a la técnica de inmunohistoquímica (IHQ) para S-100, CD44, Ki67 y E-cadherina (ECAD). Para el análisis de datos se utilizó estadística descriptiva y pruebas no paramétricas con un nivel de significancia de p&lt;0.05. En citología, todas las muestras mostraron un alto grado de criterio de malignidad y todos los tumores analizados fueron infiltrativos (N3/TIII). La expresión de CD44 fue negativa en todas las muestras y la positividad para S-100, Ki67 y ECAD fue 52.5, 50.4%, y 10%, respectivamente. Se concluye que el uso de CD44, Ki67 y ECAD junto con el análisis citológico e histopatológico incluyendo los criterios de “Breslow” puede ayudar a identificar melanomas equinos con alto grado de agresividad además de establecer un mejor pronóstico en este tipo de tumores.

Correlation of MMP-9 (Matrix Metalloproteinase 9) and SMA (Smooth Muscle Actin) expression with Basal Cell Carcinoma’s risk of recurrence

Basal Cell Carcinoma (BCC) is the most common cancer in many countries, with its incidence steadily rising. Data from the Indonesian Pathologists Association show that among 1,530 skin cancer cases, BCC was the most frequent (39.93%), followed by Squamous Cell Carcinoma (23%) and Malignant Melanoma (7.9%). According to the 2018 WHO classification, BCC is divided into Low-Risk and High-Risk groups based on the risk of recurrence. BCC invades surrounding tissues through extracellular matrix degradation and enhanced cell motility, driven by the expression of MMP-9 (Matrix Metalloproteinase 9) and SMA (Smooth Muscle Actin). This study aims to evaluate the expression of MMP-9 and SMA in BCC using immunohistochemistry and analyze their correlation with the risk of recurrence. A total of 40 paraffin blocks from BCC patients diagnosed between 2019 and 2021 at Dr. Saiful Anwar General Hospital in Malang, Indonesia, were sampled. The blocks were sectioned, stained with MMP-9 and SMA antibodies, and examined for positive expression indicated by brown staining in the cytoplasm of tumor cell and peritumoral stroma. Spearman correlation showed r = 0.811 for MMP-9 and r = 0.857 for SMA (p &lt; 0.05, CI: 95%), indicating a significant relationship between these markers and the risk of recurrence. Higher MMP-9 and SMA expression corresponded to a higher risk of BCC recurrence, suggesting their potential as prognostic biomarkers. However, further research is needed to assess recurrence risk more accurately and determine the most appropriate therapy.

Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response.

Gut bacteria are related to immune checkpoint inhibitors (ICIs). However, there is inconsistency in ICI-associated species, while the role of non-bacterial microbes in immunotherapy remains elusive. Here, we evaluated the association of trans-kingdom microbes with ICIs by multi-cohort multi-cancer analyses. We retrieved fecal metagenomes from 1,359 ICI recipients with four different cancers (metastatic melanoma [MM], non-small cell lung carcinoma [NSCLC], renal cell cancer [RCC], and hepatocellular carcinoma) from 12 published datasets. Microbiota composition was analyzed using the Wilcoxon rank test. The performance of microbial biomarkers in predicting ICI response was assessed by random forest. Key responder-associated microbes were functionally examined invitro and in mice. Trans-kingdom gut microbiota (bacteria, eukaryotes, viruses, and archaea) was significantly different between ICI responders and non-responders in multi-cancer. Bacteria (Faecalibacterium prausnitzii, Coprococcus comes) and eukaryotes (Nemania serpens, Hyphopichia pseudoburtonii) were consistently enriched in responders of ≥2 cancer types or from ≥3 cohorts, contrasting with the depleted bacterium Hungatella hathewayi. Responder-associated species in each cancer were revealed, such as F.prausnitzii in MM and 6 species in NSCLC. These signature species influenced ICI efficacy by modulating CD8+ Tcell activity invitro and in mice. Moreover, bacterial and eukaryotic biomarkers showed great performance in predicting ICI response in patients from discovery and two validation cohorts (MM: area under the receiver operating characteristic curve [AUROC]= 72.27%-80.19%; NSCLC: AUROC= 72.70%-87.98%; RCC: AUROC= 83.33%-89.58%). This study identified trans-kingdom microbial signatures associated with ICI in multi-cancer and specific cancer types. Trans-kingdom microbial biomarkers are potential predictors of ICI response in patients with cancer. Funding information is shown in the acknowledgments.

Companion diagnostics and predictive biomarkers for PD-1/PD-L1 immune checkpoint inhibitors therapy in malignant melanoma.

Programmed cell death receptor 1 (PD-1), when bound to the ligand programmed death-ligand 1 (PD-L1), can suppress cellular immunity and play a critical role in the initiation and development of cancer. Immune drugs targeting these two sites have been developed for different cancers, including malignant melanoma. The accompanying diagnostic method has been approved by the FDA to guide patient medication. However, the method of immunohistochemical staining, which varies widely due to the antibody and staining cut-off values, has certain limitations in application and does not benefit all patients. Increasing researches begin to focus on new biomarkers to improve objective response rates and survival in cancer patients. In this article, we enumerated three major groups, including tumour microenvironment, peripheral circulation, and gene mutation, which covered the current main research directions. In the future, we hope those biomarkers may be used to guide the treatment of patients with malignant melanoma.

Five-year cancer survival rates in Monastir, Tunisia

Abstract Background Cancer is a major public health problem worldwide. To the best of our knowledge, there is no Tunisian population-based registry studies investigating cancer survival in Tunisia. The objectives of our study were to estimate the five-year cancer survival rates in the province of Monastir, Tunisia. Methods We performed a retrospective cohort study including patients originating from Monastir diagnosed with cancer between 2002 and 2014. Data were collected from the cancer register of the center. Patients were followed until December 2022. Results In total, 9318 cancer cases were identified of whom 5741 were included for the survival analysis. The 5-year cancer survival rate, all sites combined, was 46% (95% CI: 45-47.3). Among the 10 most frequent cancer sites in Monastir, cancers having the lowest 5-year survival rates were lung cancer in men (18.2% (95% CI: 15.6-20.7)) and stomach cancer in both sexes (32.1% (95% CI: 23.4-40.7) and 25.3% (95% CI: 16-34.5) in men and women respectively). The cancers with the highest 5-year survival rates among men were skin cancer (other than malignant melanoma) (64% (95% CI: 54.5-73.4)), prostate cancer (59.1% (95% CI:54.7-63.4)) and colon cancer (55.1% (95% CI: 47.7-62.4). In women, cervical cancer (70% (95% CI: 61.8-78.1), skin cancer (other than malignant melanoma) (66.2% (95% CI: 55.1-77.2) and breast cancer (63.8% (95% CI:58.8-67.7)) were those with the highest 5-year survival rates. Patients ≥ 65 years had the lowest 5-year survival rates for almost all cancer sites in both genders. Conclusions Our study has shown that cancer survival rates in Tunisia remain low compared to developed countries. The widespread implementation of cancer control programs including healthy lifestyle, education, screening and early detection are urgently needed. Key messages • The 5-year cancer survival rate, all sites combined, in Monastir was 46% (95% CI: 45-47.3). • Cancers with the lowest 5-year survival rates in Monastir were lung cancer in men and stomach cancer in both sexes.

Gastric metastasis from renal cell carcinoma with submucosal invasion treated by surgical full-thickness resection: a case report

BackgroundMetastatic gastric tumors are rare and malignant melanoma, breast cancer, lung cancer, and esophageal cancer are common as primary lesions. On the other hand, renal cell carcinoma is easy to metastasize hematogenously to the whole body. However, metastasis to the stomach is rare and the detailed treatment of gastric metastasis is not mentioned. In this study, we report an uncommon case of gastric metastasis from renal cell carcinoma that underwent surgical full-thickness resection and reviewed the literature for treatment options.Case presentationThe patient was a female in her 60s and in January 2007, she underwent a transabdominal left nephrectomy for clear cell carcinoma of the left kidney. The pathological diagnosis was pT2N0M0 stage II. In October 2017, a total pancreatectomy with D2 dissection was performed for multiple pancreatic masses, in which the pathological diagnosis was pancreatic metastasis of renal cell cancer. In May 2019, an esophagogastroduodenoscopy for heartburn revealed redness and erosion in the greater curvature of the residual gastric body. The pathological diagnosis was gastric metastasis from renal cell carcinoma. No metastatic findings were observed and gastric wedge resection was performed. Pathological diagnosis of the resected specimen showed a 4-mm tumor, mainly within the mucosa and partly extended to the submucosal layer in 500 µm. The resected specimen had a clear resection margin.ConclusionsIn this study, we report a case in which a full-thickness resection was performed for gastric metastasis 12 years after renal cancer surgery and 2 years after pancreatic metastasis surgery. The patient survived 4 years and 8 months after gastric wedge resection. Although gastric metastasis often takes the form of submucosal tumors, it is necessary to select full-thickness resection for R0 resection, even in small and flat lesions.

Myocardial infarction risk across cancer subtypes - nationwide registry study

Abstract Background Progress in cancer treatments have significantly improved patient outcomes, leading to increased survival rates. However, patients with cancer continue to have higher rates of cardiovascular events an area that has traditionally not received much attention. Purpose The aim of this study was to examine the risk of myocardial infarction in patients with different types of cancer compared with age- and sex-matched population controls with benign skin cancer. Methods Patients with cancer between 2000-2016 were identified within the Danish National Patient Registry. Cox regression was used accounting for the competing risk of death reporting hazard ratios (HR) for both myocardial infarction and mortality. Models were adjusted for age, sex, hypercholesterolemia, atrial fibrillation, hypertension and anticoagulant therapies of all included subjects. Patients with a previous myocardial infarction were excluded from the analysis. Results A total of 503.616 patients were included in the final analysis of whom 355.920 had cancer with different cancer types and 147.696 were controls with benign skin cancer. The one-year outcome of myocardial infarction (Figure 1) was overall significant higher for all subtypes of cancer especially lymphoma HR 1.66 (interquartile range [IQR]: 1.45-1.89), bladder cancer HR 1.64 (IQR: 1.39-1.94), and gastrointestinal cancer HR 1.53 (IQR: 1.40-1.69). Hepatobiliary and pancreatic cancer, breast cancer and malignant melanoma had reduced but not significantly different HRs of 0.96 (IQR: 0.80-1.15), 0.92 (IQR: 0.79-1.07), and 0.76 (IQR: 0.60-0.96), respectively. The one-year competing risk of death (Figure 2) was overall higher for all subtybes of cancer especially hepatobiliary and pancreatic cancer and lung cancer with HRs of 52.11 (IQR: 50.18-54.11) and 41.62 (IQR: 40.17-43.12). Conclusion The one-year risk of myocardial infarction varied across cancer subtypes. Notably, lymphoma, bladder, and gastrointestinal cancers were associated with higher risks, whereas hepatobiliary and pancreatic, breast, and malignant melanoma cancer showed no statistically significant associations. The clinical significance of these differences must be viewed within the context of the significant competing risk of death in this cancer population.Risk Of Myocardial InfarctionCompeting Risk Of Death

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Prognostic value of patient-reported outcomes in advanced or metastatic melanoma patients treated with immunotherapy: Findings from the CheckMate-067 study

ObjectivePatient-reported outcomes (PROs) that predict survival in cancer patients have yet to be realized as practical tools for clinicians to make better treatment decisions. To identify such PROs in adults with advanced melanoma treated with immunotherapy, this study used 7.5-year follow-up data from CheckMate-067, a phase 3, randomized, double-blind study of nivolumab or nivolumab plus ipilimumab versus ipilimumab. MethodsPRO data assessed using the European Organization of Research for the Treatment of Cancer Core-30 and EQ-5D-3L at baseline and during subsequent visits after treatment initiation were pooled across treatment arms. Associations between baseline PRO or change from baseline (CFB) scores with survival outcomes (progression-free survival [PFS], overall survival [OS], and melanoma-specific survival [MSS]) were examined using Cox proportional hazards models for PFS or OS and cause-specific hazard models for MSS. ResultsBaseline and CFB scores for most PRO domains, especially for physical functioning, global health status/quality of life (GHS/QoL), fatigue, and EQ-5D visual analog scale (VAS), were prognostic of all survival outcomes. Achieving meaningful improvement/maintenance of baseline PRO scores at 12 weeks following treatment initiation predicted better survival outcomes than with meaningful worsening from baseline. ConclusionsPROs at baseline and during treatment, particularly for physical functioning, GHS/QoL, fatigue, and EQ-VAS, were prognostic of survival outcomes. This knowledge may accelerate development of prognostic tools to manage treatment in patients with previously untreated unresectable or metastatic melanoma who undergo immunotherapy.