Kaposi's Sarcoma Patients Research Articles

Similar Viral and Immune Characteristics of Kaposi Sarcoma in ART-treated People Living With HIV and Older Patients With Classic Kaposi Sarcoma.

Reemergence of human herpesvirus 8 (HHV-8)-induced Kaposi sarcoma (KS) in people living with HIV (PLWH) despite antiretroviral therapy (ART) poses a clinical challenge because they already have favorable CD4 T-cell numbers and undetectable viral loads. We observed that clinical presentation in PLWH on ART resembled classic KS found in older HIV-uninfected patients and hypothesized that immunosenescence may thus play a role in occurrence of KS on ART. We compared viral and immune factors implicated in the development of KS in ART-treated PLWH (HIV KS) and HIV-uninfected classic KS patients (cKS), compared to controls without KS (HIV Control, cControls respectively). Plasma, peripheral blood mononuclear cell, and skin tissues were obtained from 11 HIV KS and 11 cKS patients and 2 groups of age-matched controls. HIV KS participants were younger than cKS (aged 53 vs 75 years). HHV-8 genotypes did not differ between groups. Despite the younger age and a lower CD4/CD8 ratio, activated, exhausted, and senescent T-cell frequencies were similar between HIV KS and cKS. Anti-HHV-8 immunoglobulin G levels were higher and circulating HHV-8 DNA lower in HIV KS compared with cKS. Circulating platelet-derived growth factors AA-BB and granulocyte colony-stimulating factors were higher in HIV KS We observed similar levels of HHV-8 DNA and PD-1 expression in skin lesions from HIV KS and cKS patients. Altogether, early immune senescence could be involved in the development of KS in ART-treated PLWH. Higher anti-HHV-8 immunoglobulin G levels could be linked with lower circulating viral load. Such insights should help developing therapeutical strategies to prevent development and treat KS in PLWH on ART.

Association between KSHV-Specific Humoral and T Cell Responses with Recurrence of HIV-Associated Kaposi Sarcoma.

Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy, with the Kaposi sarcoma-associated herpes virus (KSHV) as its etiologic agent. Upon treatment with chemotherapy, a proportion of HIV-associated KS patients experience disease recurrence within a few months of completing treatment. We aimed at determining whether KSHV-specific adaptive immune responses were associated with KS recurrence upon complete remission. We conducted a prospective cohort study. The primary outcome was the recurrence of HIV-associated KS. An immunofluorescence assay was used to determine anti-KSHV antibodies, an enzyme-linked immunospot was conducted for T cell responses, PCR was carried out to determine KSHV status, and flow cytometry was used for CD4 counting and immunophenotyping. KSHV detection in PBMCs was high and not associated with KS recurrence-free survival (p = 0.29). Anti-KSHV antibody titers were high and not associated with recurrence-free survival (p = 0.63). KSHV-specific T cell responses dropped from baseline levels among individuals with recurrence, but the drop was not statistically significant. Individuals experiencing KS recurrence had a significantly higher proportion of T cell subsets expressing PD1, while those with sustained remission had a significant increase in CD4 T cell counts from baseline levels during the follow-up period (p = 0.02). Anti-KSHV antibodies are not a good correlate of protection from KS recurrence. T cells in individuals experiencing KS recurrence hadhigh PD1 expression, while an increase in CD4 counts was associated with sustained KS remission.

Electrochemotherapy in Kaposi's Sarcoma Patients: From the Gold Standard Strategy to Locally Advanced Cutaneous and Subcutaneous Lesions.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as a medical procedure for skin neoplasms' treatment, especially for classic Kaposi's sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and the local control of CKS disease. The primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions' treatment. In total, 19 CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt; meanwhile, 3 and 4 out of 19 patients obtained a partial response (PR), so they underwent a second and third ECT treatment, respectively. Clinical response was evaluated during the entire timeframe of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. The control of CKS skin lesions still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors' recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi's sarcoma locally advanced lesions.

Antibody profiling and predictive modeling discriminate between Kaposi sarcoma and asymptomatic KSHV infection.

Protein-level immunodominance patterns against Kaposi sarcoma-associated herpesvirus (KSHV), the aetiologic agent of Kaposi sarcoma (KS), have been revealed from serological probing of whole protein arrays, however, the epitopes that underlie these patterns have not been defined. We recently demonstrated the utility of phage display in high-resolution linear epitope mapping of the KSHV latency-associated nuclear antigen (LANA/ORF73). Here, a VirScan phage immunoprecipitation and sequencing approach, employing a library of 1,988 KSHV proteome-derived peptides, was used to quantify the breadth and magnitude of responses of 59 sub-Saharan African KS patients and 22 KSHV-infected asymptomatic individuals (ASY), and ultimately to support an application of machine-learning-based predictive modeling using the peptide-level responses. Comparing anti-KSHV antibody repertoire revealed that magnitude, not breadth, increased in KS. The most targeted epitopes in both KS and ASY were in the immunodominant proteins, notably, K8.129-56 and ORF65140-168, in addition to LANA. Finally, using unbiased machine-learning-based predictive models, reactivity to a subset of 25 discriminative peptides was demonstrated to successfully classify KS patients from asymptomatic individuals. Our study provides the highest resolution mapping of antigenicity across the entire KSHV proteome to date, which is vital to discern mechanisms of viral pathogenesis, to define prognostic biomarkers, and to design effective vaccine and therapeutic strategies. Future studies will investigate the diagnostic, prognostic, and therapeutic potential of the 25 discriminative peptides.

Kaposi's Sarcoma: Evaluation of Clinical Features, Treatment Outcomes, and Prognosis in a Single-Center Retrospective Case Series.

Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical-epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan-Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.

Clinical Significance of Elevated KSHV Viral Load in HIV-Related Kaposi's Sarcoma Patients in South Africa.

Kaposi's sarcoma (KS) is an AIDS-defining illness caused by Kaposi's sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients (n = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa. Demographic and clinical data, KS staging and response to treatment were extracted from patient files, while long-term survival was ascertained from hospital records. KSHV serology and VL and hIL-6 were determined empirically from patients' blood. All patients were HIV-positive adults, the majority of whom were on HAART at the time of recruitment. KSHV VL was detectable in 65 patients' blood (median: 280.5/106 cells (IQR: 69.7-1727.3)) and was highest in patients with S1 HIV-related systemic disease (median 1066.9/106 cells, IQR: 70.5-11,269.6). KSHV VL was associated with the S1 stage in a binomial regression controlling for confounders (adjusted odds ratio 5.55, 95% CI: 1.28-24.14, p = 0.022). A subset of six patients identified to have extremely high KSHV VLs was predominantly T1 stage with pulmonary KS, and most had died at follow-up. In our cohort, elevated KSHV VL is associated with systemic HIV-related illness in KS disease. Extremely high KSHV VLs warrant further investigation for patients potentially requiring intensive treatment and investigation for progression or diagnosis of concurrent KSHV lytic syndromes.

HIV associated malignancies presenting as acute pancreatitis: a case series.

Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra-pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP,tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

Prognostic analysis of cutaneous Kaposi sarcoma based on a competing risk model

The data regarding the prognosis of cutaneous Kaposi sarcoma (KS) was limited. The current study aimed to explore the risk factors and develop a predictive model for the prognosis of cutaneous KS patients. Data were extracted from Surveillance, Epidemiology, and End Results database from 2000 to 2018 and randomly divided into training and validation cohort. The Kaplan–Meier analysis, cumulative incidence function based on the competing risk model and Fine–Gray multivariable regression model was used to identify the prognostic factors and then construct a 5-, 10-, and 15-year KS-specific death (KSSD) nomogram for patients. The concordance index (C-index), area under the curve (AUC) of operating characteristics and calibration plots were used to evaluate the performance of the model. The clinical utility of the model was measured by decision curve analysis (DCA). In 2257 cutaneous KS patients identified from database, the overall median survival time was about 13 years. Radiotherapy (p = 0.013) and surgery (p < 0.001) could lower the KSSD, while chemotherapy (p = 0.042) and surgery (p < 0.001) could increase the overall survival (OS) of patients with metastatic and localized lesions, respectively. Race, number of lesions, surgery, extent of disease, year of diagnosis and age were identified as risk factors associated with cutaneous KS-specific survival. Performance of the nomogram was validated by calibration and discrimination, with C‐index values of 0.709 and AUC for 5-, 10-, and 15-year-KSSD of 0.739, 0.728 and 0.725 respectively. DCA indicated that the nomogram had good net benefits in clinical scenarios. Using a competing-risk model, this study firstly identified the prognostic factors, and constructed a validated nomogram to provide individualized assessment and reliable prognostic prediction for cutaneous KS patients.

A retrospective study of Kaposi's sarcoma in Hotan region of Xinjiang, China.

Kaposi sarcoma (KS) is the most common cancer in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS). In 1994, Chang and Moore discovered Kaposi sarcoma associated herpesvirus for the first time in KS lesions in AIDS patients. KS is a low-grade mesenchymal neoplasm of blood and lymphatic vessels that primarily affects the skin, although the disease may become disseminated to the lymphatic system, lungs, airways, or abdominal viscera. In this research, clinical characteristics and treatment of patients of Kaposi sarcoma were retrospectively analyzed in Hotan District, Xinjiang China. We look into the clinical traits, prognosis, and therapy of Kaposi sarcoma. From May 2017 to August 2022, 32 patients were treated in the People's Hospital of Hotan District, Xinjiang Uygur Autonomous Region, China. Twenty-two of these were classic Kaposi sarcomas (cKS), and 10 of these were Kaposi sarcomas linked to AIDS (AIDS-KS). The majority of KS patients were Uyghur. In terms of age at onset, AIDS-KS patients were younger than cKS patients. cKS and AIDS-KS are most frequently manifested in the feet and lower limbs. Ten patients with AIDS-KS have treated with combination antiretroviral therapy (combination antiretroviral therapy) combination chemotherapy, 5 of 10 patients had a complete response, 2 patients achieved partial response, the overall effective rate was 70%, and CD4 + T cells were greater than before. For cKS and AIDS-KS, the median overall survival was 56 and 50.8 months, respectively (P > .05). As a result, antiviral combination chemotherapy can also improve the prognosis of AIDS-KS patients.

Rituximab-Induced Kaposi Sarcoma in HIV-Negative Patients: A Narrative Review.

Kaposi sarcoma (KS) is a low-grade mesenchymal angioproliferative disorder that requires infection with human herpes virus 8 (HHV-8) for it to develop. It is commonly seen in HIV-positive patients and rarely in immunosuppressed HIV-negative patients. Rituximab is a monoclonal anti-CD20 chimeric murine/human immunoglobulin G antibody used to treat B cell lymphoproliferative diseases as well as a variety of autoimmune disorders. Several cases of iatrogenic Kaposi sarcoma (iKS) have been described after rituximab treatment. The purpose of this narrative review is to identify the presence of common clinical characteristics among rituximab-induced KS patients that could facilitate better management of this rare condition.

A prospective cohort study identifies two types of HIV+ Kaposi Sarcoma lesions: proliferative and inflammatory.

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS-associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One-year overall survival was 61%, and progression-free survival was 58%. The 48-week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well-controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease.

Clinical Activity of Sirolimus in Classic Kaposi’s Sarcoma Patients: Long-Term Remission of Lesions

Introduction: Kaposi’s sarcoma (KS) is a multicentric angiomatous neoplasm of lymphatic endothelium-derived cells that leads to angioproliferative diseases and affects the skin and internal organs. Currently, the main treatment options include radiotherapy, chemotherapy and targeted treatment. However, due to the low incidence rate and high malignancy, prognosis remains dismal and thus novel strategies are warranted. Methods: We treated 3 cases of KS with sirolimus, and evaluated the effectiveness and related side effects. Two were not suitable for chemotherapy, andone refused chemotherapy. Results: In this study, three patients all achieved symptom relief within three days. One patient died of pulmonary infection, and the overall survival time was 12.0 months. The other two patients had not reached disease progression, and the progression free survival time (PFS) of one patient was more than 18 months. The main adverse reaction was grade 1-2 oral mucositis, which was well controlled and well tolerated. Conclusion: This study shows the long-term remission of lesions and satisfactory safety of oral sirolimus in KS patients who are unsuitable for chemotherapy or refuse chemotherapy.

Impact of disadvantaged socioeconomic and demographic status on survival in Kaposi sarcoma.

e21581 Background: Kaposi sarcoma (KS) is a soft tissue tumor that affects a wide variety of patient populations, though it is typically seen in immunocompromised patients, including those living with organ transplant or HIV/AIDS. Patients from traditionally underserved socioeconomic and demographic populations have historically had poor outcomes across malignancies, however these populations have never been studied on a large national scale in KS. To examine how socioeconomic and demographic status affects survival in KS, we examined the National Cancer Database (NCDB); a large oncology database that includes approximately 75% of newly diagnosed cancers across the United States. Methods: We conducted a retrospective analysis of the NCDB for KS patients diagnosed from 2004 to 2019. Cases missing data for variables of interest were excluded. Overall survival (OS) was examined using Kaplan-Meier and multivariate Cox regression. Results: A total of 5,233 patients with KS were identified, with a mean age of 58 years. Most patients were male (87.1%), White (70.1%), not Spanish/Hispanic (82.7%), and had government insurance (54.3%). Comorbid conditions were described using the Charlson-Deyo Comorbidity Score (CDS), and a substantial number of patients had a score above 3 (28.6%). The mean OS for all patients was 122 months. On adjusted Cox regression, decreased OS was seen in patients over 85 years old (HR 2.14, 95% CI 1.82-2.53, p&lt;0.001) compared to patients aged 40-54 years old. Compared to White patients, Black patients had decreased OS (HR 1.24, 95% CI 1.11-1.38, p&lt;0.001); mean survival in Black patients was 113 months compared to 124 months in White patients (p&lt;0.001). Improved OS was seen in patients of Spanish/Hispanic origin (HR 0.80, 95% CI 0.70-0.91, p&lt;0.001). Any CDS greater than 1 was associated with poor OS (HR 1.46 for CDS 1, 95% CI 1.26-1.70, p&lt;0.001), and treatment at an academic facility had a protective effect (HR 0.75, 95% CI 0.69-0.82, p&lt;0.001), as did private insurance (HR 0.65, 95% CI 0.55-0.77, p&lt;0.001). Biological sex, education, income, and facility location did not independently impact survival. Conclusions: When adjusted for key demographic covariates, advanced age, Black race, and presence of comorbidities were each independently associated with decreased OS in KS patients. Improved OS was seen with Spanish/Hispanic ethnicity, treatment at an academic facility, and private insurance. To our knowledge, our study is the first to describe demographic and socioeconomic features impacting survival for KS patients at this scale. We revealed important disparities in survival and highlight the need for equitable care in KS, especially for patients of Black race.

Academic medical center access and outcomes in Kaposi sarcoma.

e21582 Background: Kaposi sarcoma (KS) is a soft tissue tumor commonly affecting the skin. It is seen in patients in immunosuppressed states, such as those with HIV/AIDS or organ transplant history. Treatment may include excision, chemotherapy, or radiotherapy depending on the location and spread of lesions. Prior studies indicate that treatment at academic facilities, which offer higher treatment volume, and access to specialized care, clinical trials, and a greater number of ancillary services, is associated with improved survival in other skin cancers, such as melanoma. In this study we aim to compare the survival and sociodemographic factors for KS patients between academic and non-academic facilities, using the largest dataset of these patients yet examined. Methods: We conducted a retrospective analysis of the National Cancer Database from 2004 to 2019 for subjects with KS, identified by ICD code 9140 (n=5,233). Factors were compared between patients seen at non-academic (NAC) (n=2,278) versus academic centers (AC), (n=2,955). Overall survival (OS) was estimated using Kaplan Meier analysis with pairwise log-rank tests for significance. Multivariate analysis was performed using binary logistic regression. Results: Most individuals in the study were White (70.1%), male (87.1%), not of Spanish or Hispanic origin (82.7%), and had government insurance (54.3%). Treatment at AC was associated with improved survival compared to NAC (median OS 184 vs. 98 months, p&lt;0.001). AC patients were younger compared to NAC patients (mean age 56.1 vs. 60.9 years old, p&lt;0.001). On adjusted logistic regression, AC were more likely to treat minority patients, including Black patients (OR 1.23, 95% CI 1.06-1.43, p=0.005) and Spanish/Hispanic patients (OR 1.26, 95% CI 1.06-1.48, p=0.007). AC were more likely to manage uninsured patients compared to patients with private (OR 0.48, 95% CI 0.39-0.60, p&lt;0.001) or government insurance (OR 0.69, 95% CI 0.55-0.86, p=0.001). Compared to the East Coast, patients in the Central U.S. (OR 0.81, 95% CI 0.71-0.93, p=0.003) and West Coast (OR 0.83, 95% CI 0.71-0.96, p=0.015) were less likely to use AC. Patients residing in high education zip codes were less likely to be treated at academic centers (p&lt;0.001). Patients in the top income quartile were more likely to be treated at AC (OR 1.42, 95% CI 1.15-1.75, p=0.001). Conclusions: Treatment at AC is associated with improved overall survival compared to NAC in KS. AC were more likely to treat younger patients, and those from racial and ethnic minorities, as well as those in the top income quartile. Less academic center use was seen in areas of higher educational attainment and by individuals with government or private insurance. While specialized care and clinical trial access may play a role in this survival benefit, access to AC may also be a surrogate marker of social determinants of health that play a role in KS outcomes. Our study supports the ongoing need for access to comprehensive care in KS.

Analysis of hospitalizations of patients with Kaposi sarcoma: A national population-based study.

e18821 Background: Kaposi sarcoma (KS) is a type of soft tissue sarcoma due to infection with human herpes virus 8 (HHV-8) and can be associated with acquired immunodeficiency syndrome [AIDS]. Recent national population data are scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with KS in the United States (U.S). Methods: Data were abstracted from the National Inpatient Sample (NIS) Database. This database is the largest collection of inpatient admission data in the U.S. It is a 20-percent stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. The numbers in the databases are weighted to optimize national estimates. Hospitalizations for patients with KS were obtained by searching for hospitalizations that contained ICD-10 code “C46” as a principal or secondary diagnosis. The principal diagnosis is the main reason for the admission, while any other diagnosis other than the principal, are secondary diagnosis. The reason for hospitalization (or principal diagnosis) was recorded in descending order of frequency based on the ICD-10 code organ system category and specific principal diagnosis. The total number of KS discharges, baseline demographic characteristics, hospital length of stay (LOS), and total hospital charges were recorded. STATA 16 was used for analysis. Since NIS contains de-identified data, Institutional Review Board (IRB) review was waived. Results: There were 32 million discharges included in the 2020 NIS database. Of those, 2,785 hospitalizations were for patients aged ≥18 years, who had either a principal or secondary ICD 10 code for KS. Patients were mainly males (91%), black (40%), mean age of 48 years, inpatient mortality of 9.3%, mean LOS of 9 days, and mean total hospital charge of 132,476 U.S dollars. The 5 most common reasons for hospitalization by ICD 10 code categories were infections (52.4%), cardiovascular (6.5%), respiratory (6.1%), neoplasm and hematologic (5.6%), and skin (5.6%). The 5 most common specific principal diagnoses for hospitalizations were Human immunodeficiency virus [HIV] disease (29.1%), sepsis (12.7%), left leg cellulitis (2.7%), pneumonia (2.2%), and Acute kidney injury (1.8%). Conclusions: Hospitalizations for KS patients are mostly black middle-aged men, with high inpatient mortality, long LOS, and significant hospital charges. Infections and HIV were the most common reasons for hospitalizations. Management of underlying HIV and measures for prevention, early detection, and prompt treatment of infections in the outpatient setting are important in preventing hospitalizations of these patients.

Abstract 27: Demographic Factors Associated with Extracutaneous Involvement in Kaposi Sarcoma

Abstract Purpose: Kaposi sarcoma (KS) is a soft tissue tumor that typically presents with red or purple skin lesions. However, extracutaneous involvement can occur in severe disease. The National Cancer Database (NCDB) compiles data from 1,400 cancer programs across the United States; to our knowledge, there has yet to be a study in the NCDB comparing demographic features and presentation of KS with cutaneous versus extracutaneous disease. Thus, there is a need to characterize the KS cohort with regards to primary site. Methods: We conducted a retrospective analysis of the NCDB from 2004 to 2019 for Kaposi sarcoma patients (n=5,587). Analysis was completed between patients with cutaneous (n=3,963) and extracutaneous (n=1,624) involvement using Pearson Chi-square and t-tests. Survival was estimated using Kaplan-Meier curves. Results: Non-cutaneous lesions made up 29.1% of diagnoses and primarily included connective/subcutaneous tissue (12.2%), as well as digestive organs (4.1%). Median survival was lower in the extracutaneous (101.7 months) cohort compared to cutaneous (131.5 months) cohort (p&amp;lt;0.001). Women were more likely to present with non-cutaneous lesions compared to men (37.3% versus 27.6%, p&amp;lt;0.001). Spanish/Hispanic subjects were less likely to have extracutaneous involvement compared to non-Spanish/Hispanic subjects (p=0.006). Patients at academic centers were less likely to have extracutaneous lesions compared to other facilities (p&amp;lt;0.001). Residing in the Central United States was associated with increased incidence of extracutaneous disease (p&amp;lt;0.001). Patients with extracutaneous disease lived further from the reporting hospital (23.95 miles) compared to patients with cutaneous (16.24 miles) involvement (p=0.004). There was no significant difference in mean age between cutaneous (58.41 years) and non-cutaneous (57.97 years) cohorts. No clear trend existed between race, insurance status, education, or income in relation to extracutaneous disease. Conclusion: To our knowledge, our study is the first to compare demographic features and trends associated with cutaneous and extracutaneous KS in the NCDB. We revealed that extracutaneous primary site is associated with poorer survival and highlighted several significant differences between the cohorts. Citation Format: Michelle Swedek, Xinxin Wu, Peter Silberstein, Victoria Vardell. Demographic Factors Associated with Extracutaneous Involvement in Kaposi Sarcoma [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 27.

Taxonomic reclassification of Kaposi Sarcoma identifies disease entities with distinct immunopathogenesis

BackgroundThe taxonomy of Kaposi Sarcoma (KS) is based on a classification system focused on the description of clinicopathological features of KS in geographically and clinically diverse populations. The classification includes classic, endemic, epidemic/HIV associated and iatrogenic KS, and KS in men who have sex with men (MSM). We assessed the medical relevance of the current classification of KS and sought clinically useful improvements in KS taxonomy.MethodsWe reviewed the demographic and clinicopathological features of 676 patients with KS, who were referred to the national centre for HIV oncology at Chelsea Westminster hospital between 2000 and 2021.ResultsDemographic differences between the different subtypes of KS exist as tautological findings of the current classification system. However, no definitive differences in clinicopathological, virological or immunological parameters at presentation could be demonstrated between the classic, endemic or MSM KS patients. Reclassifying patients as either immunosuppressed or non-immunosuppressed, showed that the immunosuppressed group had a significantly higher proportion of adverse disease features at presentation including visceral disease and extensive oral involvement, classified together as advanced disease (chi2 P = 0.0012*) and disseminated skin involvement (chi2 P < 0.0001*). Immunosuppressed patients had lower CD4 counts, higher CD8 counts and a trend towards higher HHV8 levels compared to non-immunosuppressed patients, however overall survival and disease specific (KS) survival was similar across groups.ConclusionThe current system of KS classification does not reflect meaningful differences in clinicopathological presentation or disease pathogenesis. Reclassification of patients based on the presence or absence of immunosuppression is a more clinically meaningful system that may influence therapeutic approaches to KS.

Koebner Phenomenon in Kaposi's Sarcoma: A Large Single-Center Case Series and Review of Current Knowledge.

occasional case reports have described the appearance of Kaposi's sarcoma (KS) on previously unaffected skin after incidental or accidental injury, but the association is probably under-reported. to present a large case series of patients suffering from Koebner phenomenon (KP) in KS and describe their main epidemiological, clinical, and therapeutic features. we have retrospectively analyzed our clinical and photographic records of 524 patients who had been diagnosed with KS between 2009 and 2021. 31 of 524 (6%) KS patients developed KP. Among these 31 patients, 24 (77%) had KS lesions after surgery, 4 (13%) after electrochemotherapy, laser therapy and cryotherapy, and 3 (10%) on areas affected by bullous diseases. trauma, including surgery or other medical procedures, can trigger KS, underlying the importance of treatment options which cause the least injury to the skin.

Antibody epitope profiling of the KSHV LANA protein using VirScan.

The humoral antibody response against Kaposi sarcoma-associated herpesvirus (KSHV) in infected individuals has been characterized demonstrating the latency-associated nuclear antigen (LANA) as the most antigenic KSHV protein. Despite the antigenicity of the protein, specific LANA epitopes have not been systematically characterized. Here, we utilized a bacteriophage T7 library, which displays 56-amino acid KSHV LANA peptides with 28-amino acid overlap (VirScan), to define those epitopes in LANA targeted by antibodies from a cohort of 62 sub-Saharan African Kaposi sarcoma (KS) patients and 22 KSHV-infected asymptomatic controls. Intra- and inter-patient breadth and magnitude of the anti-LANA responses were quantified at the peptide and amino acid levels. From these data, we derived a detailed epitope annotation of the entire LANA protein, with a high-resolution focus on the N- and C-termini. Overall, the central repeat region was highly antigenic, but the responses to this region could not be confidently mapped due to its high variability. The highly conserved N-terminus was targeted with low breadth and magnitude. In a minority of individuals, antibodies specific to the nuclear localization sequence and a portion of the proline-rich regions of the N-terminus were evident. In contrast, the first half of the conserved C-terminal domain was consistently targeted with high magnitude. Unfortunately, this region was not included in LANA partial C-terminal crystal structures, however, it was predicted to adopt predominantly random-coil structure. Coupled with functional and secondary structure domain predictions, VirScan revealed fine resolution epitope mapping of the N- and C-terminal domains of LANA that is consistent with previous antigenicity studies and may prove useful to correlate KSHV humoral immunity with pathogenesis.

Iatrogenic Kaposi sarcoma of the small bowel in Crohn’s disease following short-term use of immunomodulators: a case report and review of the literature

BackgroundKaposi sarcoma is a vascular tumor highly related to human herpesvirus-8 and Kaposi sarcoma–associated herpesvirus. Kaposi sarcoma usually manifests as skin or mucosal lesions; involvement in visceral organs such as the gastrointestinal tract is rare. Kaposi sarcoma can occur in immunocompromised patients receiving immunosuppressive therapy, in which case it is known as iatrogenic Kaposi sarcoma or drug-induced Kaposi sarcoma. Intestinal Kaposi sarcoma in patients with inflammatory bowel disease is extremely rare.Case presentationA 46-year-old East Asian male with recently diagnosed Crohn’s disease was administered azathioprine and prednisolone; however, the patient complained of persistent abdominal pain and diarrhea following treatment. Endoscopy revealed small bowel Kaposi sarcoma. The patient was treated with systemic chemotherapy successfully without relapse.ConclusionsThis is the fifth case of Kaposi sarcoma developed over the small intestine in a patient with Crohn’s disease following administration of immunomodulators. Additionally, this case indicated that even short-term immunomodulator use can induce Kaposi sarcoma in patients with inflammatory bowel disease. Thus, in patients with inflammatory bowel disease, if symptoms are aggravated or do not abate after immunomodulators prescription, and before intending to upgrade immunomodulators, endoscopy should be considered. Finally, chemotherapy can also be considered if both medication withdrawal and surgical intervention are not feasible.