Oncology最新文献

{"title":"MUC17 is a potential new prognostic biomarker and promotes pancreatic cancer progression in obstructive jaundice.","authors":"Eleonóra Gál, István Menyhárt, Zoltán Veréb, Lajos Kemény, László Tiszlavicz, Zoltán Márton Köhler, Anikó Keller-Pintér, Dávid Rakk, András Szekeres, Tamás Takács, László Czakó, Péter Hegyi, Boshra Yosef, Viktória Venglovecz","doi":"10.1159/000541874","DOIUrl":"https://doi.org/10.1159/000541874","url":null,"abstract":"<p><p>Our working group has previously shown that bile acids (BAs) accelerate carcinogenic processes in pancreatic cancer (PC) in which mucin 4 (MUC4) expression has a central role. However, the role of other mucins in PC are less clear, especially in bile-induced cancer progression. The study aim was to investigate expression of MUC17 in BAs- or human serum-treated pancreatic ductal adenocarcinoma (PDAC) cell lines and use different assays with RNA silencing/overexpression to study the role of MUC17 in cancer progression. Protein expression of MUC17 was evaluated in 55 human pancreatic samples by immunohistochemistry, and Kaplan-Meier survival analysis was used to compare survival curves. Expression of MUC17 increased in PDAC patients, especially in obstructive jaundice (OJ) and the elevated MUC17 expression associated with poorer overall survival (10.66±1.99 vs. 15.05±2.03 months; Log rank: 0.0497). Treatment of Capan-1 and AsPC-1 cells with BAs or with human serum obtained from PDAC + OJ patients enhanced the expression of MUC17, as well as the proliferative potential of the cells, whereas knockdown of MUC17 alone or in combination with MUC4 decreased BAs-induced carcinogenic processes. Our results demonstrated that MUC17 has a central role in bile-induced PC progression, and in addition to MUC4, this isoform also can be used as a novel prognostic biomarker.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib versus Sorafenib Second-Line Therapy in Patients with Hepatocellular Carcinoma Progressed to Atezolizumab plus Bevacizumab: A Retrospective Real-World Study.","authors":"Mara Persano, Andrea Casadei-Gardini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Federico Rossari, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Alberto Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Mariangela Bruccoleri, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Luigi Mascia, Silvia Foti, Silvia Camera, Fabio Piscaglia, Mario Scartozzi, Stefano Cascinu, Margherita Rimini","doi":"10.1159/000541018","DOIUrl":"10.1159/000541018","url":null,"abstract":"<p><strong>Introduction: </strong>The most frequently used first-line treatment in patients with advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab. Upon progression after this treatment, the standard of care in many countries is sorafenib, due to the lack of reimbursement for other drugs. Several randomized trials are currently underway to clarify the best second-line therapy in patients with HCC. This real-world study aimed to compare outcomes reached by lenvatinib and sorafenib second-line therapy in this setting.</p><p><strong>Methods: </strong>The overall cohort included 891 patients with HCC from 5 countries treated with atezolizumab plus bevacizumab in first-line setting between October 2018 and April 2022. At the data cut-off (May 2022), 41.5% of patients were continuing a first-line treatment, 5.5% were lost at follow-up, and 53.0% of patients had progressive disease after first-line therapy. 51.5% of patients with progressive disease received a second-line treatment, while 48.5% did not receive any subsequent therapy. Between patients receiving second-line treatment, 11.1% of patients underwent transarterial chemoembolization, 21.0% received sorafenib, 35.4% underwent lenvatinib, and 32.5% were treated with other drugs.</p><p><strong>Results: </strong>Lenvatinib second-line subgroup achieved a median overall survival (mOS) of 18.9 months, significative longer (p = 0.01; hazard ratio [HR]: 2.24) compared to sorafenib subgroup that reached a mOS of 14.3 months. The multivariate analysis highlighted albumin-bilirubin 1 grade (p < 0.01; HR: 5.23) and lenvatinib second-line therapy (p = 0.01; HR: 2.18) as positive prognostic factors for OS. The forest plot highlighted a positive trend in terms of OS in favor of patients treated with lenvatinib second-line regardless of baseline characteristics before first-line therapy.</p><p><strong>Conclusion: </strong>These results suggest that, in patients with HCC progressed to first-line atezolizumab plus bevacizumab, lenvatinib second-line therapy is associated to an improved survival compared to sorafenib.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immune Microenvironment in Prostate Cancer: A Comprehensive Review.","authors":"Rene Novysedlak, Miray Guney, Majd Al Khouri, Robin Bartolini, Lily Koumbas Foley, Iva Benesova, Andrej Ozaniak, Vojtech Novak, Stepan Vesely, Pavel Pacas, Tomas Buchler, Zuzana Ozaniak Strizova","doi":"10.1159/000541881","DOIUrl":"10.1159/000541881","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a malignancy with significant immunosuppressive properties and limited immune activation. This immunosuppression is linked to reduced cytotoxic T cell activity, impaired antigen presentation, and elevated levels of immunosuppressive cytokines and immune checkpoint molecules. Studies demonstrate that cytotoxic CD8+ T cell infiltration correlates with improved survival, while increased regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are associated with worse outcomes and therapeutic resistance. Th1 cells are beneficial, whereas Th17 cells, producing interleukin-17 (IL-17), contribute to tumor progression. Tumor-associated neutrophils (TANs) and immune checkpoint molecules, such as PD-1/PD-L1 and T cell immunoglobulin-3 (TIM-3) are also linked to advanced stages of PCa. Chemotherapy holds promise in converting the \"cold\" tumor microenvironment (TME) to a \"hot\" one by depleting immunosuppressive cells and enhancing tumor immunogenicity.</p><p><strong>Summary: </strong>This comprehensive review examines the immune microenvironment in PCa, focusing on the intricate interactions between immune and tumor cells in the TME. It highlights how TAMs, Tregs, cytotoxic T cells, and other immune cell types contribute to tumor progression or suppression and how PCa's low immunogenicity complicates immunotherapy.</p><p><strong>Key messages: </strong>The infiltration of cytotoxic CD8+ T cells and Th1 cells correlates with better outcomes, while elevated T regs and TAMs promote tumor growth, metastasis, and resistance. TANs and natural killer (NK) cells exhibit dual roles, with higher NK cell levels linked to better prognoses. Immune checkpoint molecules like PD-1, PD-L1, and TIM-3 are associated with advanced disease. Chemotherapy can improve tumor immunogenicity by depleting T regs and myeloid-derived suppressor cells, offering therapeutic promise.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Autologous Stem Cell Transplantation in First-Line Treatment and at Relapse in Elderly Patients with Multiple Myeloma.","authors":"Eva-Maria Klein, Sejla Hujic, Kaya Miah, Axel Benner, Maximilian Merz, Uta Bertsch, Niels Weinhold, Hartmut Goldschmidt, Sandra Sauer","doi":"10.1159/000541541","DOIUrl":"10.1159/000541541","url":null,"abstract":"<p><strong>Introduction: </strong>Although recent data suggest that melphalan high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT) is safe and effective in eligible multiple myeloma (MM) patients up to the age of 75 years, its value in elderly MM patients is still controversially discussed.</p><p><strong>Methods: </strong>We retrospectively analyzed 607 MM patients ≥60 years old, who were admitted to our institution for first-line or salvage HDT/ASCT between January 2007 and October 2018. We assigned them to three groups according to age at HDT/ASCT: 60-64 years (S1), 65-69 years (S2) and ≥70 years (S3). We compared progression-free and overall survival, duration of hospitalization, complications, transfers to intermediate or intensive care unit, readmissions after discharge and deaths within 100 days after HDT/ASCT between these groups.</p><p><strong>Results: </strong>Age did not impact progression-free and overall survival after first-line and salvage HDT/ASCT. Patients ≥70 years old at first HDT/ASCT had a longer hospitalization compared to patients 60-64 years old; however, the difference in the length of hospitalization was only marginal. Rates of febrile neutropenia, mucositis, transfers to intermediate or intensive care unit, readmissions after discharge, and deaths within 100 days after HDT/ASCT were similar in the 3 age groups of patients receiving first or salvage HDT/ASCT. Patients with a Charlson Comorbidity Index ≥2 receiving first HDT/ASCT had a higher risk for a transfer to intermediate or intensive care unit.</p><p><strong>Conclusion: </strong>Our analysis shows that HDT/ASCT is safe and effective in eligible elderly MM patients in first-line treatment and at relapse. A careful patient selection according to biological rather than chronological age is of crucial importance.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lobectomy with Lymph Node Dissection Benefits N3 Stage Non-Small Cell Lung Cancer Patients: A Population-Based Study.","authors":"Zhoujunyi Tian, Jin Zhang, Deruo Liu, Chaoyang Liang","doi":"10.1159/000541634","DOIUrl":"10.1159/000541634","url":null,"abstract":"<p><strong>Introduction: </strong>There remain controversies about the role of surgery for N3 stage non-small cell lung cancer (NSCLC) patients.</p><p><strong>Methods: </strong>N3 stage NSCLC patients were identified from the US National Cancer Institute Surveillance, Epidemiology, and End Results database (2010-2020). Survival analysis and multivariate regression models were used to adjust covariates and analyze factors associated with survival. Propensity score matching was used to balance selection bias.</p><p><strong>Results: </strong>Of 6,473 included patients, 121 received treatment that included lobectomy with mediastinal lymph node dissection. Overall survival (OS) was significantly prolonged in the lobectomy group than in the nonsurgery group (median survival time [MST]: 57 vs. 16 months; log-rank p &lt; 0.001). A total of 403 patients were matched, and OS was significant longer in the lobectomy group (MST: 51 vs. 16 months; log-rank p &lt; 0.001). Multivariate regression analyses indicated that lobectomy was independently associated with improved OS (hazard ratio [HR] 0.398, 95% confidence interval [CI] 0.302-0.526; p &lt; 0.001) and lung cancer-specific death (LCSD) (subhazard ratio [SHR] 0.343, 95% CI: 0.249-0.474; p &lt; 0.001).</p><p><strong>Conclusion: </strong>Compared with nonsurgical treatment modalities, lobectomy with lymph node dissection was associated with improved OS and LCSD in selected N3 stage NSCLC patients.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial and Geographic Differences in Endometrial Cancer Death.","authors":"Jia Yi Tan, Yong Hao Yeo, Jia Yean Thong, Sabera Saleh, Kelly Mbenga, Gunwant Guron, Hamid S Shaaban","doi":"10.1159/000541683","DOIUrl":"10.1159/000541683","url":null,"abstract":"<p><strong>Introduction: </strong>In the USA, endometrial cancer incidence rose by 4.5% annually from 1999 to 2015, reaching 18 per 100,000 women, with a disproportionate impact on African American women. Despite advancements in endometrial cancer research, racial disparities in mortality rates persist. Our retrospective cohort study aimed to investigate the mortality trends and disparities among patients with endometrial cancer in the USA.</p><p><strong>Methods: </strong>Patients with endometrial cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were compared across different races and geographical regions.</p><p><strong>Results: </strong>From 1999 to 2020, endometrial cancer accounted for 90,145 deaths in the USA. Overall, the AAMRs of endometrial cancer increased significantly from 2.50 (95% CI, 2.41-2.58) in 1999 to 3.94 (95% CI, 3.85-4.04) per 100,000 individuals in 2020, with an AAPC of +2.23 (95% CI, 1.39-3.07). The highest AAMR was observed among African Americans (2.69 [95% CI, 2.65-2.74]), followed by whites (1.44 [95% CI, 1.43-1.45]), Hispanics (1.16 [95% CI, 1.13-1.20]), Asians (1.00 [95% CI, 0.96-1.04]), and American Indians (0.99 [95% CI, 0.88-1.10]). The highest AAMR from endometrial cancer was recorded in the Northeast region (1.73 [95% CI, 1.71-1.76]).</p><p><strong>Conclusion: </strong>There was an increasing trend of mortality rates from endometrial cancer in the last 2 decades, which disproportionately affected African Americans. Targeted interventions are warranted to address the mortality disparities among patients with endometrial cancer.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA in Routine Clinical Practice.","authors":"Shaheenah Dawood, Nippun Sandhir, Marwan Akasheh, Maroun El Khoury, Sonia Otsmane, Muath Alnassar, Omalkhair Abulkhair, Fadi Farhat, Steve Olsen","doi":"10.1159/000541571","DOIUrl":"10.1159/000541571","url":null,"abstract":"<p><strong>Introduction: </strong>Next-generation sequencing (NGS) of tumor DNA can detect actionable drivers and help guide therapy for patients with advanced-stage cancers. While tissue-based genotyping is considered a standard of care, blood-based genotyping is emerging as a valid alternative. Tumor genomic profiles may vary by region, and data from the Middle East and North Africa (MENA) are not widely available. This study elucidates the genomic landscape of advanced solid cancers in patients from the MENA region by retrospectively analyzing results from NGS circulating tumor DNA (ctDNA) testing.</p><p><strong>Methods: </strong>In routine clinical practice, 926 plasma samples from 767 patients with advanced cancers from the MENA region were profiled using a comprehensive NGS assay (Guardant360®). We conducted a pan-cancer analysis and sub-analyses focusing on lung, breast, and colorectal cancers.</p><p><strong>Results: </strong>In the pan-cancer group, TP53 (58.5%), EGFR (20.4%), and KRAS (18.9%) were the most frequently mutated genes. EGFR (10.2%), FGFR1 (4.9%), and PIK3CA (4.9%) showed the most amplifications, while fusions were observed in 2.7% of patients, including ALK, FGFR2, and RET. For lung adenocarcinoma, EGFR (30.5%), KRAS (19.3%), and ERBB2 (4.6%) were the most frequently identified alterations among the genes recommended for evaluation by the National Comprehensive Cancer Network (NCCN). In patients with breast cancer, PIK3CA (35.3%), ESR1 (21.7%), and BRCA1/2 (13.3%) had the most prevalent alterations among NCCN-recommended genes. In colorectal cancer, KRAS (39.0%), NRAS (8.0%), and BRAF (V600E, 4.0%) were the most observed mutations among genes recommended by the NCCN. Comparing this cohort to publicly available Western and Eastern datasets also indicated similarities (including PIK3CA in breast cancer) and variances (including EGFR in lung adenocarcinoma) in key genes of interest in the analyzed cancer types.</p><p><strong>Conclusion: </strong>Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Analysis of the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors at The Ottawa Hospital Cancer Center over the Last Decade Including COVID-19 Pandemic Period.","authors":"Mohammad Alrehaili, William J Phillips, Tim Asmis, Michael Vickers, Horia Marginean, Rachel Goodwin","doi":"10.1159/000540907","DOIUrl":"10.1159/000540907","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of neuroendocrine tumors (NETs) is rising. Our objective was to assess trends in gastroenteropancreatic (GEP)-NETs diagnosis (June 2010 to June 2021) at TOHCC and to explore whether early COVID-19 pandemic data impacted these trends.</p><p><strong>Methods: </strong>This was a single-center retrospective chart review of data collected from June 2010 to June 2021. We searched all databases, including OACIS/EPIC, PACS, and OPIS and found 647 GEP-NET patients. Descriptive analyses were performed using frequencies and related percentages.</p><p><strong>Results: </strong>Of 647 patients with GEP-NETs, the small bowel was the most common primary location (n = 210, 32.4%), followed by the pancreas (n = 118, 18.2%), and unknown primary location (n = 99, 15.3%). Most of the cases were classified as metastatic or locally advanced at the initial presentation. There has been no significant variation in the frequency distribution of these cases over the last decade. Stages 1 and 2 were found in 158 cases (23.8%), and lower gastrointestinal (GI) tumors were the most common disease among them (n = 88, 55.7%). There were 5 lower GI cases in 2010-2011 and average number per registration year was 5.5 until 2016-2017, after which time the number of cases increased to 10, 15, 11, and 13 during the last 4 years. Regarding early-stage pancreatic and upper GI NETs, the total number of cases was 52 (32.9%) and 18 (11.4%), respectively. The average number of cases per registration year for pancreatic tumors was 4.7, while that for upper GI tumors was 1.6 over the last decade.</p><p><strong>Discussion: </strong>At our center, most GEP-NETs presented in an advanced setting. Small bowel is the most common location overall. The incidence of early-stage disease has increased. Disease detection for all GEP-NETs was consistent throughout the last decade, except for the lower GI cases that have increased since mid-2017, perhaps reflecting the adoption of Ontario FIT testing. Despite endoscopy closures and disruption of some diagnostic services during the pandemic, cases of GEP-NETs for all stages did not decrease.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Cancer Detection in Diverse Skin Tones by Machine Learning Combining Audio and Visual Convolutional Neural Networks.","authors":"Bruce N Walker, Travis Wayne Blalock, Rebecca Leibowitz, Yoram Oron, Daphne Dascalu, Eli Omid David, Avi Dascalu","doi":"10.1159/000541573","DOIUrl":"10.1159/000541573","url":null,"abstract":"<p><strong>Introduction: </strong>Skin cancer (SC) is common in fair skin (FS) at a 1:5 lifetime incidence for nonmelanoma skin cancer. In order to assist clinicians' decisions, a risk intervention technology was developed, which combines a dual-mode machine learning of visual and sonified (pixel to sound) data. The addition of an audio technology enhances malignant features of lesions, increases sensitivity and was previously validated under a prospective clinical setting in FS. In dark skin (DS), although rare by a 10-30 factor, skin cancer is diagnosed at more advanced stages resulting in a delayed diagnosis and affecting life quality and expectancy. It is known as well that SC diagnostic accuracy by machine learning in DS is decreased as compared to FS. The present study tests the use of sonification aided by artificial intelligence algorithms to compare diagnostics of different skin tones.</p><p><strong>Methodology: </strong>Biopsy-validated smartphone images were diagnosed in a retrospective study by a dual audio-visual convoluted neural network. A total of 60 Fitzpatrick I-III were compared to 72 Fitzpatrick IV-VI. A dichotomous diagnostic output, either malignant or benign, was assessed for sensitivity, specificity and area under the curves (AUCs) for the receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>ROC curve analytics indicated an AUC of 0.858 (95% CI: 0.795-0.921) and 0.856 (95% CI: 0.759-0.953) for fair and DS (p = NS). Sensitivity of Fitzpatrick I-III skin and Fitzpatrick IV-VI were 84.4% (71.8-96.9) and 79.6% (63.4-93.8), respectively (p = NS). Specificity of Fitzpatrick I-III skin and Fitzpatrick IV-VI were 84.2% (72.6-95.8) and 85.3% (73.4-97.2), respectively (p = NS). The positive predictive and negative predictive values as well as accuracy (0.817 vs. 0.847) were all within the same range (p = NS).</p><p><strong>Conclusions: </strong>The results demonstrate that the dual-modality classifier identifies skin cancer of FS and DS similarly well. Sonification of malignant signs of a skin lesion demonstrates promising results, even with smartphone images, which should be considered as a tool to achieve more effective and accessible healthcare.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demographic Trends, Co-Alterations, and Imatinib Resistance across Genomic Variants in Gastrointestinal Stromal Tumors: An AACR Project GENIE Analysis.","authors":"Hunter Stecko, Sidharth Iyer, Diamantis Tsilimigras, Timothy M Pawlik","doi":"10.1159/000541454","DOIUrl":"10.1159/000541454","url":null,"abstract":"<p><strong>Introduction: </strong>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract, the treatment of which represents a significant breakthrough in targeted cancer therapy. Given its overall rare nature, genomic differences and clinical implications between demographic groups have not been previously investigated.</p><p><strong>Methods: </strong>Anonymized demographic, clinical, and genomic data from 1,559 GIST patients in the American Association for Cancer Research Project GENIE database were analyzed using cBioPortal and custom Python scripts. Data on patient demographics, genomic alterations, and co-occurrence genetic alerations were collected and classified according to clinical implications using the OncoKB database. χ2 tests for differences in genomic alterations were used across various demographic factors and mutual exclusivity analysis was employed to identify co-mutation patterns.</p><p><strong>Results: </strong>Male patients demonstrated higher incidence of PDGFRA mutation (14.56% vs. 8.05%; p &lt; 0.001), while female patients had higher likelihood of NF1 mutations (7.46% vs. 3.23%; p = 0.001). Asian patients had higher alteration rates at KIT (85.59%; p = 0.002). Co-occurrence analysis revealed KIT alterations frequently co-occurred with CDKN2A (q &lt; 0.001), MTAP (q = 0.045), and PTEN (q = 0.056), while there was mutual exclusivity with PDGFRA (q &lt; 0.001), NF1 (q &lt; 0.001), and BRAF (q = 0.015). CDKN2A alterations co-occurred with MTAP (q &lt; 0.001) and PIK3CA (q = 0.015), while being mutually exclusive with TP53 (q = 0.002) and NF1 (q = 0.007). Trends were similar among patients who had received no prior medical treatment. Imatinib-resistant mutations were more common among male patients (25.6% vs. 18.9%; p = 0.0056) and individuals under 55 (27.3% vs. 20.9%; p = 0.0228). Among patients with imatinib-resistant mutations, 77.78% had sunitinib resistance, while 70.25% maintained sensitivity to ripretinib.</p><p><strong>Conclusion: </strong>Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}