Malignancy Spectrum最新文献

{"title":"A case report: Complications of trans arterial embolization in managing ruptured hemorrhage of hepatocellular carcinoma","authors":"Gang Tong,&nbsp;Yang Hua,&nbsp;Renhua Huang,&nbsp;Junwen Hu","doi":"10.1002/msp2.70025","DOIUrl":"https://doi.org/10.1002/msp2.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) rupture and hemorrhage is one of the critical emergencies in HCC, with a high mortality rate upon occurrence. The mortality rate after rupture and hemorrhage is nearly 25%, while the recurrence rate of bleeding is approximately 20%, with a mortality rate exceeding 50%. Even after bleeding cessation, related complications pose significant challenges for treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>Here, we report a case of multi-vessel rupture and hemorrhage in HCC, where initial hemostasis was successfully achieved via trans arterial embolization (TAE), but another vessel ruptured and bled again within 48 h. The total blood loss in this case was about 3300 mL, accompanied by severe complications such as infection, liver function deterioration, hepatic encephalopathy, and malnutrition. Additionally, we conducted a literature review on the mechanisms and treatment of HCC rupture and hemorrhage, aiming to provide insights and lessons for its diagnosis and management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>(1) After TAE for ruptured hepatocellular carcinoma with hemorrhage, it is still necessary to be vigilant against the possibility of secondary hemorrhage. During the TAE procedure, precise embolization should be achieved as much as possible to reduce liver function damage. (2) After ruptured hepatocellular carcinoma with hemorrhage, complications such as abdominal infection, hepatic encephalopathy, malnutrition, and deterioration of liver function need to be watched out for. Early identification and active intervention can help patients achieve better prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"204-208"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcomatoid carcinoma arising in the pulmonary artery","authors":"Huiting Zhang,&nbsp;Chunlei Li,&nbsp;Binglin Zhang,&nbsp;Hongzhu Long,&nbsp;Ting Yao,&nbsp;Zhenguo Zhai,&nbsp;Wanmu Xie","doi":"10.1002/msp2.70026","DOIUrl":"https://doi.org/10.1002/msp2.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcomatoid carcinoma is a rare and aggressive malignancy with a poor prognosis, capable of arising in diverse tissues. Pulmonary artery sarcomatoid carcinoma is particularly uncommon and highly invasive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>We present the case of a 40-year-old male who experienced dry cough and dyspnea, and was subsequently diagnosed with a mass obstructing the bilateral main pulmonary artery, predominantly involving the left main branch shortly after contracting COVID-19. Histopathological analysis of a lung biopsy and positron emission tomography (PET) scan confirmed the diagnosis of sarcomatoid carcinoma involving the bilateral main pulmonary artery. Following six cycles of combined chemotherapy and immunotherapy, the patient's condition remained relatively stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case report aims to discuss the clinical presentation, diagnostic approach, and therapeutic management of this rare condition, thereby contributing to the broader understanding of sarcomatoid carcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"209-213"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of aerobic exercise on worst joint pain in postmenopausal breast cancer women receiving aromatase inhibitors: A systematic review and meta-analysis","authors":"Saim Mahmood Khan,&nbsp;Jawairya Muhammad Hussain,&nbsp;Manahil Mubeen,&nbsp;Maryam Tariq,&nbsp;Zarnab Saleem,&nbsp;Marium Amjad,&nbsp;Laiba Bukhari,&nbsp;Iffa Habib,&nbsp;Hafiz Waqas Naseer,&nbsp;Mahnoor Khan,&nbsp;Hassan Saleem,&nbsp;Surraiya Riaz Mahmood Khan,&nbsp;Hudda Amjad,&nbsp;Aina Lashari","doi":"10.1002/msp2.70029","DOIUrl":"https://doi.org/10.1002/msp2.70029","url":null,"abstract":"&lt;p&gt;Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), especially joint pain, have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a major cause of treatment termination. Aerobic exercise has emerged as a promising nonpharmacological intervention to counteract AIMSS in this population. This study aimed to perform a systematic review and meta-analysis to assess the effect of aerobic exercise on aromatase inhibitor-induced worst joint pain in postmenopausal breast cancer. A systematic literature search was performed using ClinicalTrials.gov, PubMed, and the Cochrane Library that yielded 1415 records. Studies comparing the effect of aerobic exercise with usual care on the worst joint pain through brief pain inventory (BPI) scoring in postmenopausal women with breast cancer receiving aromatase inhibitor therapy were included. For each group, the mean change from baseline and standard deviation (SD) of worst joint pain (BPI score) were calculated. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were conducted to explore heterogeneity based on exercise intervention. Three randomized controlled trials (&lt;i&gt;n&lt;/i&gt; = 297) were included. Pooled analysis showed no significant overall effect of exercise compared with control (standardized mean difference [SMD] = −0.16; 95% CI [−1.45, 1.14]; &lt;i&gt;p&lt;/i&gt; = 0.65; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 74%). Subgroup analysis indicated a significant difference by exercise type (&lt;i&gt;p&lt;/i&gt; = 0.003), suggesting exercise modality influenced outcomes. Aerobic exercise, evaluated in two RCTs, significantly reduced worst joint pain (SMD = −0.41; 95% CI [−0.50, −0.32]; &lt;i&gt;p&lt;/i&gt; = 0.01; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0%), indicating consistent benefit across studies. In contrast, the single study assessing Nordic walking showed no significant improvement (SMD = 0.56; 95% CI [−0.08, 1.19]; &lt;i&gt;p&lt;/i&gt; = 0.08). Risk-of-bias assessment revealed variability across studies, with one trial rated low risk, one with some concerns, and one at high risk, which may partly explain the observed heterogeneity (&lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 74%). Aerobic exercise interventions did not show an overall significant effect on the worst joint pain. However, subgroup analysis revealed that multi-component aerobic exercise programs were associated with significant pain reduction, while the study with only Nordic walking intervention was not. Considering the clinical burden of aromatase inhibitor-induced musculoskeletal symptoms, aerobic exercise can be a potentially useful non-pharmacologic adjunct to endocrine therapy. However, given the variation in the assessed risk of bias among the included studies, these outcomes should be interpreted with due caution. To confirm these results and determine the optimal exercise type and duration for managing aromatase inhibitor–associated musculoskeletal symptoms in breast cancer surviv","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"186-195"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bowel obstruction in advanced malignancies: An evaluation of patient outcomes at a tertiary cancer centre","authors":"Harriet O'Rourke,&nbsp;Mahendra Naidoo,&nbsp;Oliver Piercey,&nbsp;Linda Mileshkin,&nbsp;Michael T. Fahey,&nbsp;Tamara Vu,&nbsp;Alexander G. Heriot,&nbsp;Jeanne Tie,&nbsp;Orla McNally,&nbsp;Anne Hamilton","doi":"10.1002/msp2.70027","DOIUrl":"https://doi.org/10.1002/msp2.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malignant bowel obstruction (MBO) is a highly morbid complication of advanced intra-abdominal malignancies. This study aims to identify clinicopathologic factors and intervention strategies associated with improved survival and reduced rates of re-obstruction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single centre, retrospective data analysis was performed for all consecutive patients admitted with MBO to a tertiary cancer centre in Melbourne, Australia over a 2-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a total of 102 patients with 137 admission episodes for MBO. Median age was 62 years, and 55 patients (54%) were female. 61 patients (60%) had a gastrointestinal primary (colorectal, gastric or appendiceal), while 17 patients (16%) had a gynaecological primary and 24 (24%) other primaries. Median overall survival was 120 days (95% confidence interval (CI) [76, 167]). 41 patients (40%) died within 90 days of initial admission with MBO. Clinicopathological variables associated with reduced 90-day survival included hypoalbuminaemia (odds ratio [OR] = 3.33 for serum albumin &lt; 30 g/L, 95% CI [1.43, 7.69]) and peritoneal disease (OR = 5.80, 95% CI [2.26, 14.9]). 41 patients (40%) received surgical management. We identified no factors significantly associated with the decision for surgical rather than conservative management. Of the 113 total admissions that reached discharge, 55 (49%) were followed by patient readmission within 90 d. Almost half (48%) of patients were referred to the inpatient palliative care service and this was associated with a reduction in the odds of 90 d readmission (OR = 0.31, 95% CI [0.14, 0.71]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MBO heralds a poor prognosis, with high rates of readmission, morbidity and mortality. Careful patient selection is imperative to identify patients likely to benefit from operative management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"196-203"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From RCD pathways to precision oncology: A spatially-aware approach in HCC","authors":"Haider Imran,&nbsp;Zahra A. Haque,&nbsp;Minhal Imaan,&nbsp;Muhammad A. Aslam","doi":"10.1002/msp2.70028","DOIUrl":"https://doi.org/10.1002/msp2.70028","url":null,"abstract":"&lt;p&gt;This Letter to the Editor is being written to respond to the article by Yao et al. (2025), which explores the role of non-apoptotic regulatory cell death (RCD) pathways in hepatocellular carcinoma (HCC) and their application in molecular prognostication.&lt;/p&gt;&lt;p&gt;HCC is one of the most common primary liver cancers, which accounts for 600,000 deaths annually, with a prognosis of 500,000–1,000,000 new annual cases [&lt;span&gt;1&lt;/span&gt;]; hence, it remains a major global health challenge. Despite the advent of immune checkpoint inhibitors (ICIs), therapeutic responses remain suboptimal. Many patients exhibit intrinsic or acquired resistance due to immunosuppressive tumor microenvironment (TME), impaired antigen presentation, tumor heterogeneity, and microbiome-driven influences [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Nonapoptotic RCD, which includes ferroptosis, pyroptosis, and necroptosis, was presented by Yao et al. as a new axis affecting tumor immune behavior and resistance mechanisms [&lt;span&gt;3&lt;/span&gt;]. Weighted gene co-expression network (WGCNA) and nonnegative matrix factorization (NMF) were applied to stratify HCC patients into three subtypes based on RCD gene expression, with ramifications for survival, immune infiltration, and drug responsiveness. A six-gene prognostic model was proposed to differentiate high- and low-risk patients, providing a more dynamic alternative to static biomarkers [&lt;span&gt;3, 4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;This study highlighted a significant advancement in functional stratification and precision oncology for HCC. However, by integrating spatial transcriptomics, the potential can be further amplified as this will allow anatomical mapping of gene expression within the TME. Offering a spatial lens through which to interpret molecular profiles, with site-specific risks, RCD-driven suppressive niches, and spatially distinct immune-excluded areas as discovered by this approach [&lt;span&gt;5, 6&lt;/span&gt;]. For example, immune-cold tumor regions that usually escape detection can be visualized, targeted, and analyzed using site-adapted therapies.&lt;/p&gt;&lt;p&gt;Moreover, the synergy of spatial omics with AI-enhanced digital pathology holds promise for real-time, image-guided biomarker prediction and dynamic patient monitoring [&lt;span&gt;7&lt;/span&gt;]. Such an integration opens a next-generation frontier for tailoring immunotherapies and predicting treatment response with unprecedented granularity.&lt;/p&gt;&lt;p&gt;We applaud the authors' efforts to connect clinical knowledge with computational biology, and we encourage future research to validate their model prospectively across diverse, multiethnic cohorts. Incorporating RCD-based stratification within spatially aware, AI-integrated frameworks could redefine prognostication and therapy personalization in HCC, ushering in a new era of precision oncology.&lt;/p&gt;&lt;p&gt;Haider Imran contributed to writing the manuscript and reviewed the manuscript. Zahra Ali Haque contributed to editing the manuscript and came up with the concept. Minhal Imaan contributed ","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"214-215"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypofractionated versus conventionally fractionated radiotherapy for breast cancer in patients with reconstructed breast","authors":"Saim Mahmood Khan,&nbsp;Jawairya Muhammad Hussain,&nbsp;Manahil Mubeen,&nbsp;Aleeza Hasan,&nbsp;Haider Fizza,&nbsp;Muskan Shaikh,&nbsp;Maheen Khan,&nbsp;Surraiya Riaz Mahmood Khan,&nbsp;Syeda Faiqa Batool,&nbsp;Yuri André Ramírez Paliza,&nbsp;Syeda Saman Gul","doi":"10.1002/msp2.70024","DOIUrl":"https://doi.org/10.1002/msp2.70024","url":null,"abstract":"<p>Breast cancer (BC) is the most prevalent and destructive tumor in developing countries. The implementation of mammography screening programs has enabled access to appropriate therapeutic interventions, including adjuvant endocrine therapy and breast-conserving surgery; earlier diagnosis translates into a wider survival-rate range, making hypofractionated radiotherapy (HFRT) the preferred option. This review examines the current literature comparing the two radiation therapies, HFRT and conventional radiotherapy (CR), with reconstructed breasts, focusing on efficacy, toxicity, cosmetic outcomes, quality of life (QOL), and cost-effectiveness. A comprehensive literature search was conducted using major scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search focused on articles published primarily in English, from 2010 to 2024, and the period is about 15 years. The following search terms and Boolean operators were used: “hypofractionated radiotherapy” OR “hypofractionation” AND “breast cancer” AND “toxicity” OR “complications” OR “reconstruction” OR “quality of life” OR “HFRT versus CFRT” OR “intensity-modulated radiation therapy” OR “proton therapy”. CR can be safely replaced with HFRT in terms of overall survival and local recurrence rates. HFRT is associated with lesser risks of both acute and chronic side effects, breast complications, increased patient satisfaction, and reduced breast problems. In addition, new radiotherapy modalities, such as intensity-modulated radiation therapy, have shown great potential in targeting tumors. In treating BC, HFRT is gradually becoming standard, especially for patients who undergo reconstruction after surgery. Its low toxicity and equal effectiveness make it a key element in improving the QOL of BC survivors. It is recommended that future studies focus on long-term outcomes to provide better care to patients.</p>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"173-185"},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mirdametinib (Gomekli) wins FDA approval, bringing relief to NF-1 patients with surgically inoperable plexiform neurofibromatosis worldwide","authors":"Memuna J. Zeb","doi":"10.1002/msp2.70020","DOIUrl":"https://doi.org/10.1002/msp2.70020","url":null,"abstract":"&lt;p&gt;Neurofibromatosis type 1 (NF-1) is an autosomal dominant, complex multi-system disorder that primarily affects the skin and nervous system. It is characterized by mutations in the &lt;i&gt;NF1&lt;/i&gt; gene on chromosome 17, leading to abnormal production of neurofibromin protein. Common symptoms include café au lait spots, Lisch nodules, neurofibromas, plexiform neurofibromas, scoliosis, vision disorders, and learning and mental disabilities [&lt;span&gt;1&lt;/span&gt;]. Managing NF-1 can be challenging because it is a lifelong disorder in which chronic pain is a prominent feature; consequently, opioids are prescribed and somnolence is frequently reported. Surgical interventions to remove tumors can also result in long-term physical impairments [&lt;span&gt;2&lt;/span&gt;]. In recent years, new treatments like Selumetinib (Koselugo) have been approved. However, its effectiveness is mainly limited to children, and it can cause adverse effects like vomiting, raised creatinine phosphokinase, dry skin, and diarrhea [&lt;span&gt;3&lt;/span&gt;]. A new development is the U.S. Food and Drug Administration's (FDA) approval on February 11, 2025 of mirdametinib (Gomekli), a mitogen-activated protein kinase kinase (MEK) inhibitor, for the treatment of adults and pediatric patients aged 2 years and older with NF-1-associated surgically inoperable plexiform neurofibromas. [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Loss of neurofibromin protein in NF-1 patients causes Ras signaling dysregulation. This results in MEK hyperactivation, driving uncontrolled cell growth and tumor formation. Mirdametinib, a specific noncompetitive MEK inhibitor (MEKi), blocks MEK activity, reducing hyperactivation of Ras and shrinkage of surgically inoperable plexiform neurofibromatosis. A Phase II trial assessed the safety and efficacy of mirdametinib in adolescents and adults of age ≥ 16 years with &lt;i&gt;NF1&lt;/i&gt;-related plexiform neurofibromas. The results showed that mirdametinib is well-tolerated and effective, with a 42% partial response rate and at least 20% tumor shrinkage by volume [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The ReNeu trial, a pivotal Phase IIb study, evaluated the efficacy of mirdametinib in 114 patients. The results demonstrated a substantial confirmed objective response rate, durable reductions in plexiform neurofibromas volume, and clinically meaningful improvements in pain and health-related quality of life [&lt;span&gt;6&lt;/span&gt;]. Crucially, mirdametinib stands out as a treatment distinct from traditional approaches like selumetinib, as it has been proved to be effective in the treatment for both children and adults.&lt;/p&gt;&lt;p&gt;Although mirdametinib represents a breakthrough for plexiform neurofibromas in NF-1, it carries a broad side-effect profile. Most commonly, cutaneous toxicities, including acneiform rash, eczema, seborrheic dermatitis, paronychia, and xerosis, have been reported [&lt;span&gt;7&lt;/span&gt;], along with fatigue, profound changes in bile acid metabolism leading to nausea, vomiting, diarrhea [&lt;span&gt;8&lt;/span&gt;], as well as MEKi-associated re","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"171-172"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy + immunotherapy + anti-vascular therapy and firmonertinib + capmatinib prolong OS in EGFR-mutated and MET amplification following disease progression on osimertinib plus savolitinib: A case report of NSCLC","authors":"Ting Xu,&nbsp;Xiaohua Wang,&nbsp;Wanlin Shen,&nbsp;Mingxia Yang","doi":"10.1002/msp2.70018","DOIUrl":"https://doi.org/10.1002/msp2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgound</h3>\u0000 \u0000 <p>The combination of osimertinib and savolitinib as second-line treatment after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance can significantly improve median progression-free survival (mPFS), objective response rate (ORR), and duration of remission (DOR). The combination therapy is safe and controllable, with no new safety signals or unexpected toxicity. However, the mechanism of drug resistance for tumor progression after dual-targeted therapy is currently unclear, and there is no clinical data reference for treatment after drug resistance. This case suggests some treatment options for lung adenocarcinoma patient after dual-targeted therapy with osimertinib and savolitinib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case presentation</h3>\u0000 \u0000 <p>A patient with <i>EGFR</i>-mutated lung adenocarcinoma developed mesenchymal–epithelial transition factor (<i>MET</i>) amplification-related resistance after first-line almonertinib. Subsequent sequential regimens—osimertinib plus savolitinib, chemo-immuno-antiangiogenesis therapy, and finally furmonertinib plus capmatinib—each yielded transient benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The report shows that the combination of chemotherapy and immunotherapy, as well as the dual-targeted therapy of firmonertinib and capmatinib, prolonged the overall survival of the patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This case suggests some treatment options for lung adenocarcinoma patient after dual-targeted therapy with osimertinib and savolitinib. The results indicated that traditional treatment or the combination of MET-TKI with another targeted therapy may improve the prognosis of patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"151-158"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune infiltration in TP53 missense mutant contributes to poor prognosis in hepatocellular carcinoma, unlike CTNNB1 mutations","authors":"Durgadevi Veeraiyan,&nbsp;Vishnu Kurpad,&nbsp;Vinayak Munirathnam,&nbsp;Chaitra V.,&nbsp;Sonal Asthana,&nbsp;Akhileshwar Namani,&nbsp;Tapas Patra","doi":"10.1002/msp2.70015","DOIUrl":"https://doi.org/10.1002/msp2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is one of the deadliest cancer over the world. In this study, we aimed to determine the most critical molecular event in HCC patients with tumor protein p53 (<i>TP53</i>) or catenin beta 1 (<i>CTNNB1</i>) mutations, and to explore how these two mutations differ in their impact on HCC prognostication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an integrated comparative analysis of exome and transcriptome data from The Cancer Genome Atlas (TCGA) for HCC patients. Patient prognosis and correlation with the immune infiltration characteristics were performed. HCC cell line based in vitro experiments were also performed to validate the mechanistic insights.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 3-year progression-free survival (PFS) analysis of HCC patients with <i>TP53</i> mutations indicated a significantly poorer clinical outcome compared to those with <i>CTNNB1</i> mutations. Functional annotation of the <i>TP53</i> mutant cohort revealed a substantial upregulation of genes associated with immune regulation, while the <i>CTNNB1</i> mutant cohort displayed a prominent activation of metabolic pathways. Further comparative analysis and in vitro experiments showed that <i>TP53</i> missense mutations activated the signal transducer and activator of transcription 3 (STAT3) signaling pathway, which fostered neutrophil infiltration and enhanced the enrichment of regulatory T (Treg) cells by secreting specific inflammatory molecules in the tumor microenvironment. Notably, treatment with a an STAT3 inhibitor suppressed the expression of these inflammatory molecules, underscoring how an immunosuppressive tumor microenvironment in the <i>TP53</i> mutant cohort contributes to a poor prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides valuable insights, revealing that HCC patients with <i>TP53</i> missense mutations exhibit a distinct immune profile associated with poorer clinical outcome compared to those with <i>CTNNB1</i> mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"117-127"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetuin-A:adiponectin ratio (FAR) as a critical biomarker in obesity-induced colorectal cancer?","authors":"Chandrani Fouzder,&nbsp;Subhadip Mukhopadhyay,&nbsp;Aditi Banerjee,&nbsp;Suprabhat Mukherjee","doi":"10.1002/msp2.70021","DOIUrl":"https://doi.org/10.1002/msp2.70021","url":null,"abstract":"&lt;p&gt;Obesity is one of the burning lifestyle-related health problems of the current generation, affecting more than one-third of the global population. Obese individuals face a severe risk of various cancers, particularly concerning colorectal cancer (CRC), which has an extremely low survival rate among affected patients [&lt;span&gt;1&lt;/span&gt;]. In fact, obesity is linked to 4%–8% of global cancer cases, and obese cancer patients face a 17% higher risk of mortality [&lt;span&gt;2&lt;/span&gt;]. A recent report examined the relationship between obesity and four obesity-related cancers, namely cancers of the colon, rectum, pancreas, and kidney [&lt;span&gt;2&lt;/span&gt;]. The study analyzed cancer incidence data from 42 countries and found positive correlation coefficients of 0.27 and 0.33 for colon cancer and rectal cancer, respectively [&lt;span&gt;2&lt;/span&gt;]. Obesity-related CRC is associated with chronic low-grade inflammation, which may promote the progression of colorectal neoplasia through the inflammation–dysplasia–tumor sequence, particularly in early-onset cases. [&lt;span&gt;3&lt;/span&gt;]. The risk of CRC in overweight/obese women under 50 years old has doubled, and a high-fat diet (HFD) consumed by a mother can lead to CRC in both mother and foetus [&lt;span&gt;4&lt;/span&gt;]. Obesity modulates the CRC microenvironment, where the fat components are readily taken up by the tumor but not the CD8&lt;sup&gt;+&lt;/sup&gt; T cells, thereby blocking tumor infiltration and blunting cancer immunotherapy [&lt;span&gt;5&lt;/span&gt;]. In fact, HFD causes metabolic dysregulation by gut microbiota, increases the levels of lysophosphatidic acid, and promotes colorectal tumorigenesis [&lt;span&gt;6, 7&lt;/span&gt;]. Similarly, the increase in the levels of palmitic acid in the blood caused by an HFD, which then leads to the activation of Toll-like receptor 4 (TLR4) in the colonic tissue, promotes growth, inflammatory pathogenesis, and CRC metastasis, and is directly associated with poor survival rates in patients with CRC [&lt;span&gt;8&lt;/span&gt;]. Among the events, obesity-induced and/or obesity-associated pro-inflammatory milieu is majorly signaled by the adipokine, called fetuin-A or alpha-2-Heremans-Schmid glycoprotein (AHSG), whose serum level is positively correlated with visceral adipose tissue mass and body mass index (BMI, &gt;30 kg/m&lt;sup&gt;2&lt;/sup&gt;). Fetuin-A binds to TLR4 to induce inflammation-mediated fatty colon, interacts with membrane annexins (II and VI), and activates the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway to promote the proliferation of CRC cells. In contrast, adiponectin, a 30-kDa adipokine secreted by the adipocytes, prevents obesity through anti-inflammatory and hypolipidemic actions, and low adiponectin levels are associated with obesity, other inflammatory diseases, and poor prognosis across multiple cancer subtypes, including CRC [&lt;span&gt;8&lt;/span&gt;]. Individuals with the highest serum levels of adiponectin possess around 60% less risk of CRC. Exogeneous adiponectin treatment was found to restric","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"167-170"},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}