Journal of Immunotherapy and Precision Oncology最新文献

{"title":"Prevalence of Molecular Mutations in Non-Small Cell Lung Cancer and Current Treatment Approaches in the MENA Region: Systematic Review and Expert Opinion.","authors":"AbdulAziz AlJassim, Aladdin Kanbour, Fathi Azribi, Muath AlNassar, Riadh Mohsen, Sahar Dawod, Selvaraj Giri, Michael Nasr Kamal, Ali AlJabban, Layth Mula-Hussain, Bader Alshamsan, Emad Anwar","doi":"10.36401/JIPO-24-35","DOIUrl":"10.36401/JIPO-24-35","url":null,"abstract":"<p><p>Over the past decade, the discovery of immunotherapy and targeted therapy has set new standards for the management of advanced non-small cell lung cancer (NSCLC). This study aims to investigate the prevalence of <i>ALK</i>, <i>EGFR</i>, <i>KRAS</i>, <i>ROS1</i>, <i>MET</i>, <i>BRAF</i>, and <i>HER2</i> mutations in patients with NSCLC within the Middle East and North Africa (MENA) region and to assess the current state of molecular testing and targeted treatments in the Gulf Cooperation Council (GCC) region. The systematic literature review was performed using PubMed, Google Scholar, and Google searches to identify studies on the prevalence of <i>ALK</i>, <i>EGFR</i>, <i>KRAS</i>, <i>ROS1</i>, <i>MET</i>, <i>BRAF</i>, and <i>HER2</i> mutations in patients with NSCLC in the MENA region. Additionally, 10 experts from the GCC region were interviewed to provide insights into molecular mutation testing, the challenges faced, and the current approaches to targeted therapies. The prevalence of <i>ALK</i>, <i>EGFR</i>, <i>KRAS</i>, <i>ROS1</i>, <i>MET</i>, and <i>BRAF</i> mutations was 7.9% (95% CI, 6.69-9.03%), 24% (95% CI, 22.05-25.41%), 19.7% (95% CI, 15.29-24.07%), 2.2% (95% CI, 0.77-3.57%), 4.7% (95% CI, 2.29-7.07%) and 3.7% (95% CI, 1.54-5.80%), respectively. <i>HER2</i> mutation data were unavailable. Treatment generally adhered to international guidelines, with therapy selection based on tumor stage, molecular profile, and drug availability. Expert opinions highlighted significant advancements in molecular diagnostics and targeted therapies but also pointed out the challenges in standardizing and implementing these techniques across the GCC region. This review underscores the importance of personalized and region-specific approaches to NSCLC treatment, given the significant differences in mutation patterns in the MENA region. Further research is needed to gain a more comprehensive understanding of the prevalence and effect of driver mutations across broader MENA countries to inform future treatment strategies.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 3","pages":"233-241"},"PeriodicalIF":3.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029851","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":"Circulating Tumor DNA as a Prognostic Biomarker for Selecting Participants to Early Phase Clinical Trials.","authors":"Sammy Shaya, Okezie Uche-Ikonne, Bedirhan Kilerci, Julie Stevenson, Alastair Greystoke, Natalie Cook, Fiona C Thistlethwaite, Louise Carter, Donna M Graham, Matthew G Krebs","doi":"10.36401/JIPO-25-11","DOIUrl":"10.36401/JIPO-25-11","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with advanced solid tumors may be considered for early phase clinical trials investigating the safety, tolerability, and dosing of experimental therapies. Optimizing participant selection is critical to maximize clinical benefit and meet trial endpoints with fewer participants. One in six participants does not meet routine life expectancy requirements (>3 months), highlighting the need for improved prognostication. Variant allele frequency (VAF) in circulating tumor DNA (ctDNA) correlates with overall survival (OS) in advanced solid tumors. We aimed to derive an optimal VAF threshold as a prognostic biomarker to enhance participant selection.</p><p><strong>Methods: </strong>ctDNA testing was performed as part of the TARGET (NIHR Clinical Research Network CPMS ID 39172) and TARGET National (NCT04723316) prospective cohort studies, in patients with advanced solid tumors referred for early phase clinical trials. Maximum (maxVAF) and mean VAF (meanVAF) were compared in their association with OS and ability to delineate favorable and poor outcomes at set threshold points using hazard ratios (HRs). Optimal thresholds of VAF were explored using receiver operating characteristic curve analysis to predict 3-month landmark OS. Univariable and multivariable analysis was performed to determine whether VAF was an independent prognostic marker.</p><p><strong>Results: </strong>Of 631 patients, 587 had evaluable ctDNA results. MeanVAF and maxVAF exhibited similar correlation with OS (r_s = -0.32 vs -0.35, respectively) and similar prognostic utility at matched threshold points. A maxVAF value of 4% was selected as optimal for prognostic subgrouping (area under curve 0.77). OS was 5.9 versus 12.1 months (<i>p</i> < 0.0001) for patients with more than 4% and 4% or less maxVAF, respectively. Multivariable analysis confirmed more than 4% maxVAF as independently associated with reduced 3-month landmark OS (HR 2.17 [1.76-2.70], <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>VAF is an independent prognostic marker in patients with advanced solid tumors, with 4% maxVAF deemed optimal for delineating favorable and poorer prognostic subgroups in this patient cohort. Further validation and integration into existing prognostic scores are warranted.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 3","pages":"222-232"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029682","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":"Immunotherapy and Targeted Therapies in Sarcoma: Proposed Synergy with Combination Treatment.","authors":"Aleksandra Watson, Gina D'Amato, Emily Jonczak, Steven Bialick, Jonathan Trent","doi":"10.36401/JIPO-25-10","DOIUrl":"10.36401/JIPO-25-10","url":null,"abstract":"<p><p>The combination of targeted therapies and immunotherapies for advanced and metastatic sarcomas has been proposed owing to the enhanced effect of antiangiogenic therapies on the tumor microenvironment. We found eight studies published to date assessing the effectiveness of combined multitargeted vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors with immune checkpoint inhibitors (ICIs) in sarcoma. It is difficult to draw conclusions owing to limited data and primarily single-arm studies, although initial literature appears promising and requires further study. It remains unknown which sarcoma subtypes may derive the most benefit owing to the limited literature. Benefit was seen primarily in angiosarcoma (AS) and alveolar soft part sarcoma (ASPS), as well as in other tumor subtypes, with few patients achieving complete response (CR). The patients who achieved CRs had desmoplastic small round cell tumor (DSRCT), AS, and chondrosarcoma (CS). Mixed results were found in patients with leiomyosarcoma (LMS), gastrointestinal stromal tumor (GIST), and bone sarcomas, although combination therapy appears to be less effective in these subtypes. Further studies are required to explore optimal treatment agents and dosing strategies to improve both efficacy and tolerability. Although initial results are promising in select patients, phase 3 randomized controlled trials are necessary to determine true treatment effect with combination therapy versus VEGF-inhibitor or ICI alone.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 3","pages":"212-221"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029844","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":"Exceptional Response to Immunotherapy-based Treatment in Compound <i>EGFR</i>-Mutated Oligometastatic Pulmonary Sarcomatoid Carcinoma: A Case Report.","authors":"Ayushi Gianchandani, Darshana Desai, Janani Sambath, Darshana Patil, Prashant Kumar, Shambhavi Singh, Chetan Madre, Ruturaj Deshpande, Anjali Parab, Niyati Shah, Darshit Shah, Pritam Kataria, Shrikanth Atluri, Marzi Mehta, Aditya Shreenivas, Rajan Datar, Razelle Kurzrock, Sewanti Limaye","doi":"10.36401/JIPO-25-7","DOIUrl":"10.36401/JIPO-25-7","url":null,"abstract":"<p><p>Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with limited treatment options and poor prognosis. <i>EGFR</i> mutations generally respond to tyrosine kinase inhibitors (TKIs)-based targeted therapy but are typically associated with resistance to immunotherapy. We report a case of oligometastatic PSC harboring compound <i>EGFR</i> mutations (p.G719C and S768I). The patient exhibited disease progression despite sequential treatment with EGFR TKIs, including osimertinib, afatinib, and mobocertinib, in combination with chemotherapy. The treatment strategy was then shifted to immunotherapy with pembrolizumab alongside carboplatin and paclitaxel, leading to a remarkable response. Given the oligometastatic nature of the disease and the sustained response, bilateral adrenalectomy was performed, revealing a complete pathological response. The patient remains disease-free posttreatment, with no evidence of recurrence on follow-up imaging. This case challenges the conventional paradigm that <i>EGFR</i>-mutated NSCLC does not benefit from immunotherapy, highlighting the potential for an alternative treatment approach in rare subtypes such as PSC. Our findings emphasize the importance of comprehensive molecular profiling and a personalized treatment strategy to optimize outcomes in aggressive and refractory lung cancers.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 3","pages":"206-211"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029827","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":"Abstracts Presented at the 2024 Emirates Oncology Conference: November 15-17, 2024, Abu Dhabi, United Arab Emirates.","authors":"","doi":"10.36401/JIPO-25-X4","DOIUrl":"https://doi.org/10.36401/JIPO-25-X4","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 3","pages":"194-205"},"PeriodicalIF":3.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029700","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":"More Than Medicine: The Hope, Hurdles, and Hidden Costs of IgG Therapy.","authors":"Christopher Boldt, Huifang Lu","doi":"10.36401/JIPO-25-X5","DOIUrl":"10.36401/JIPO-25-X5","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 3","pages":"191-193"},"PeriodicalIF":3.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029821","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":"Anti-PD-1 Therapy for Patients with Advanced Cholangiocarcinoma: Ready for Prime Time?","authors":"Gagandeep Brar, Rachna T Shroff","doi":"10.36401/JIPO-25-X3","DOIUrl":"https://doi.org/10.36401/JIPO-25-X3","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"181-183"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078395","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":"Exceptional Response in a Patient with mRCC Through Precision-Guided Treatment Involving Immunotherapy Rechallenge with Temsirolimus and Bevacizumab.","authors":"Ashkan Adibi, Ünal Metin Tokat, Esranur Aydın, Eylül Özgü, Şevval Nur Bilgiç, Nalan Akgül Babacan, Onur Tutar, Razelle Kurzrock, Mutlu Demiray","doi":"10.36401/JIPO-25-3","DOIUrl":"https://doi.org/10.36401/JIPO-25-3","url":null,"abstract":"<p><p>Comprehensive genomic profiling (CGP) and the subsequent discussions in molecular tumor boards (MTBs) are becoming an integral part of personalized cancer care. The patient with metastatic renal cell carcinoma (mRCC) presented here demonstrated an absence of a favorable response accompanied by adverse events after receiving dual immunotherapy with nivolumab plus ipilimumab in combination with a poly (adenosine diphosphate-ribose) polymerase inhibitor, niraparib. This determination was made based on the initial CGP report and the initial MTB. Following the progression of the disease and the emergence of immune-related adverse events, a second CGP was conducted, and several subsequent MTBs were held. The decision was made to transition the patient's treatment to temsirolimus plus bevacizumab, with the rechallenge of immunotherapy with pembrolizumab. The response evaluation revealed a complete radiographic and molecular response. This case study underscores the mounting significance of precision oncology in the management of mRCC, thereby suggesting that mammalian target of rapamycin inhibitor may augment the efficacy of immunotherapy in select patients based on their genomic findings. A digital poster of this case is included in the supplemental materials.</p>","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"184-190"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078396","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":"Selinexor in Uveal Melanoma: A Hopeful Step or Just Another Hurdle?","authors":"Carlos Ayala de Miguel, Roberto Borea, Christian Rolfo","doi":"10.36401/JIPO-25-X2.1","DOIUrl":"https://doi.org/10.36401/JIPO-25-X2.1","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"177-180"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969628","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":"Olaparib and Durvalumab in Patients with DNA Damage Repair Alterations and Biochemically Recurrent Prostate Cancer.","authors":"Karen A Autio, Deaglan J McHugh, Dana E Rathkopf, Han Xiao, Swathi Merugu, Phillip Wong, Mehrin Jan, Tanya B Dorff, Elisabeth I Heath, Howard I Scher","doi":"10.36401/JIPO-24-36","DOIUrl":"10.36401/JIPO-24-36","url":null,"abstract":"","PeriodicalId":16081,"journal":{"name":"Journal of Immunotherapy and Precision Oncology","volume":"8 2","pages":"172-176"},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028559","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}