2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T5f5,Aberrant alternative splicing (AS) events have been implicated in cancer progression; however, their role in metastatic renal cell carcinoma (mRCC) remains underexplored. This study aims to identify AS events associated with clinical benefits from immune checkpoint inhibitors and targeted therapies in mRCC. We conducted a retrospective analysis on 101 patients with mRCC who received systemic therapy and underwent RNA sequencing. Patients were divided into subgroups based on ICIs (alone or in combination) and targeted therapies. Responders and non-responders were classified according to Response Evaluation Criteria in Solid Tumors V.1.1 criteria. Differential gene expression and splicing analyses were performed between responders and non-responders in each cohort. Novel AS events were analyzed for their potential to generate peptide neoantigens through major histocompatibility complex (MHC) class I binding predictions. Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. AS analysis revealed 461 differentially spliced events between responders and non-responders in the ICI cohort and 253 in the targeted therapy cohort, with intron retention as the predominant motif. Thirteen unique AS events were enriched in responders, including This study provides a comprehensive analysis of AS events in mRCC, highlighting intron retention as potential biomarkers for treatment response. Identified AS-derived neoantigens may serve as potential targets for adoptive cell therapy strategies.31:Tab4, Purpose Aberrant alternative splicing (AS) events have been implicated in cancer progression; however, their role in metastatic renal cell carcinoma (mRCC) remains underexplored. This study aims to identify AS events associated with clinical benefits from immune checkpoint inhibitors and targeted therapies in mRCC. Materials and methods We conducted a retrospective analysis on 101 patients with mRCC who received systemic therapy and underwent RNA sequencing. Patients were divided into subgroups based on ICIs (alone or in combination) and targeted therapies. Responders and non-responders were classified according to Response Evaluation Criteria in Solid Tumors V.1.1 criteria. Differential gene expression and splicing analyses were performed between responders and non-responders in each cohort. Novel AS events were analyzed for their potential to generate peptide neoantigens through major histocompatibility complex (MHC) class I binding predictions. Results Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. AS analysis revealed 461 differentially spliced events between responders and non-responders in the ICI cohort and 253 in the targeted therapy cohort, with intron retention as the predominant motif. Thirteen unique AS events were enriched in responders, including PTPN6 and ACTN1 . Predictive neoantigen analysis identified high MHC class I binding potential in peptides from AS events in IFFO1 and ZNF692 . High splice burden was linked to an immunogenic tumor microenvironment, characterized by enriched antigen processing and adaptive immune responses. Conclusions This study provides a comprehensive analysis of AS events in mRCC, highlighting intron retention as potential biomarkers for treatment response. Identified AS-derived neoantigens may serve as potential targets for adoptive cell therapy strategies. 32:T72a,In the time since the last Clinical Practice Committee review of treatment of women with endometrial cancer in 2021, the field of gynecologic oncology has seen significant changes in endometrial cancer from understanding risk factors, addition of molecular staging, and expanded use of maintenance and targeted therapies. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease continued to rise. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer, including increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress. The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, Document Review Panel, and the Board of Directors prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice Committee and subject matter experts. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses.33:T50d,A PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20).34:Tc42,Melanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and outcomes in routine practice. To examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma. This cohort study assessed a longitudinal, propensity score (PS)-matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023. Era of melanoma diagnosis (2007-2012 vs 2018-2019). The primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts. A PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20). This cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system-wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.35:Tf49,ImportanceMelanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and outcomes in routine practice.ObjectiveTo examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma.Design, Setting, and ParticipantsThis cohort study assessed a longitudinal, propensity score (PS)–matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023.ExposuresEra of melanoma diagnosis (2007-2012 vs 2018-2019).Main Outcomes and MeasuresThe primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts.ResultsA PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P &lt; .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (&gt;52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20).Conclusions and RelevanceThis cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system–wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Targeted Therapy: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Targeted Therapy (modality). Clinician-written summaries and actionable practice insights. 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Individual cited RCTs may carry higher evidence levels.","value_numeric":null}],"summaries":{"what_studied":"This Series paper reviews the evolving treatment landscape for early-stage resectable non-small-cell lung cancer (NSCLC), covering neoadjuvant and perioperative immunotherapy, targeted therapies, and radiotherapy, with a focus on evidence from randomised trials.","key_result":"Perioperative immunotherapy and targeted therapies have established a new standard of care for resectable early-stage NSCLC, moving beyond the modest survival gains of surgery plus platinum-based chemotherapy alone; however, key uncertainties remain around optimal sequencing, treatment duration, patient selection, and escalation or de-intensification strategies.","limitations":"This is a narrative review/Series paper, not a primary trial — no original patient-level data are presented. Conclusions depend on the quality and completeness of the cited randomised trials. Specific subgroup analyses and long-term survival data for newer regimens may still be maturing.","practice_takeaway":"Clinicians treating resectable early-stage NSCLC should consider perioperative immunotherapy or targeted therapy as the new standard, while remaining attentive to ongoing uncertainties around sequencing, biomarker-driven patient selection, and whether to escalate or de-intensify treatment in specific populations."}},{"doi":"10.1016/s2352-3026(26)00127-4","pmid":"42685741","title":"High time for risk-adapted treatment in mantle cell lymphoma","journal_title":"The Lancet Haematology","journal_issn":"2352-3026","published_at":"2026-09-02T00:00:00.000Z","url":"https://doi.org/10.1016/s2352-3026(26)00127-4","source_score":23,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:31:59.698Z","updated_at":"2026-09-08T06:31:59.698Z","tags":[{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"condition","value":"Mantle Cell Lymphoma","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"modality","value":"BTK Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"warning","value":"Impact flag 'practice_changing' reflects the authors' stated goal of replacing age-based with biology-based treatment paradigms, but this is aspirational pending prospective trial validation.","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"warning","value":"No original patient data are presented; all conclusions are expert opinion and literature synthesis.","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00127-4","tag_type":"warning","value":"Specific targeted therapies and combination regimens are discussed conceptually but not named explicitly in the abstract — modality tags reflect general themes inferred from the MCL treatment context.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates the current landscape of risk stratification and treatment in mantle cell lymphoma (MCL), focusing on how biological markers (TP53 mutations/deletions, blastoid histology, Ki-67 index, measurable residual disease) can drive risk-adapted therapy selection over age-based approaches.","key_result":"TP53 mutations/deletions, blastoid histology, and high Ki-67 consistently identify high-risk patients; positive measurable residual disease (MRD) serves as a surrogate endpoint for inadequate response and potential treatment modification. Indolent MCL markers may support chemotherapy-free strategies.","limitations":"This is a narrative/opinion review without original patient data; specific biomarker thresholds and combination strategies require prospective validation; harmonization of multiparameter biomarkers across centers is not yet established.","practice_takeaway":"Screen MCL patients for TP53 mutations/deletions, blastoid histology, and Ki-67 at diagnosis to guide risk stratification beyond age alone. Monitor MRD as a surrogate endpoint to identify patients who may need treatment escalation or modification."}},{"doi":"10.1245/s10434-026-20383-z","pmid":"42584752","title":"Changes in Outcomes of Hepatic Cytoreduction for Neuroendocrine Liver Metastases over Two Decades: From Major Hepatectomy to Parenchyma-Sparing Approaches","journal_title":"Annals of Surgical Oncology","journal_issn":"1068-9265","published_at":"2026-08-12T00:00:00.000Z","url":"https://doi.org/10.1245/s10434-026-20383-z","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-22T06:53:43.368Z","updated_at":"2026-08-22T06:53:43.368Z","tags":[{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"condition","value":"Neuroendocrine Liver Metastases","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"condition","value":"Neuroendocrine Tumor","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Hepatic Cytoreduction","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Liver-Parenchyma-Sparing Surgery","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Major Hepatectomy","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Percutaneous Ablation","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Somatostatin Analog","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"modality","value":"Transarterial Embolization","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"sample_size","value":"n=293","value_numeric":293},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"warning","value":"Institution(s) involved in the study are not specified in the abstract, limiting generalizability assessment.","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"warning","value":"Sex distribution is not explicitly reported in the abstract; the 'mixed' sex tag is inferred from the general population context.","value_numeric":null},{"paper_doi":"10.1245/s10434-026-20383-z","tag_type":"warning","value":"The study period spans 25 years, during which both surgical techniques and systemic therapies changed substantially — the two-period grouping may not isolate the independent effect of parenchyma-sparing surgery from concurrent advances in oncologic care.","value_numeric":null}],"summaries":{"what_studied":"This retrospective study compared outcomes of hepatic cytoreduction for neuroendocrine liver metastases (NELM) in 293 patients over two periods: an earlier period (EP, 1998–2008, n=132) and a later period (LP, 2009–2023, n=161), examining the shift from major hepatectomy to liver-parenchyma-sparing cytoreduction (LPSC) and its association with survival.","key_result":"The LP cohort had a markedly better 10-year OS (67.4% vs. 44.2%, P<0.001) and a lower rate of major hepatectomy (32.9% vs. 60.0%, P<0.001). Major hepatectomy was independently associated with worse OS (HR 1.74, 95% CI 1.02–2.98, P=0.043), consistent after propensity score matching.","limitations":"Retrospective single- or multi-center design with inherent selection bias; two-period grouping may conflate multiple confounding changes in surgical technique, patient selection, and systemic therapy over 25 years; propensity score matching cannot fully account for unmeasured confounders.","practice_takeaway":"Where oncologically feasible, favor parenchyma-sparing cytoreduction over major hepatectomy for NELM — it preserves future treatment options and is associated with significantly better long-term survival. Integrating modern systemic agents (somatostatin analogs, targeted therapies) and local therapies at progression appears to further improve outcomes."}},{"doi":"10.1158/0008-5472.can-25-4262","pmid":"42171656","title":"Evolutionary Antifragile Therapy Is a Treatment Strategy to Suppress Drug Resistance by Exploiting Dose–Response Convexity","journal_title":"Cancer Research","journal_issn":"0008-5472","published_at":"2026-06-23T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13283037/","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:51.802Z","updated_at":"2026-06-27T13:27:51.802Z","tags":[{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"condition","value":"Cancer","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"condition","value":"Drug Resistance","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"study_design","value":"Preclinical In Vivo Study with Mathematical Modeling","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"warning","value":"Sample size (N) is not reported in the abstract; the sample_size tag has been omitted.","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"warning","value":"The abstract does not specify the cancer type(s) or cell lines studied, so condition tags are generalized to 'Cancer.' The study appears to involve both mathematical modeling and in vivo experiments, but the relative weight of each is unclear from the abstract alone.","value_numeric":null},{"paper_doi":"10.1158/0008-5472.can-25-4262","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — the findings are preclinical; clinical translation is not yet established.","value_numeric":null}],"summaries":{"what_studied":"This study investigated whether the convexity or concavity of tumor dose–response curves could predict how treatment fluctuations (uneven vs. continuous dosing) affect the evolution of drug resistance to targeted therapies in cancer.","key_result":"Convex dose–response curves predicted that continuous (even) dosing outperforms high/low intermittent (uneven) dosing; this was validated in vivo. Resistance onset rate was found to be a concave (antifragile) function, meaning fluctuations accelerate resistance, while the tumor cell response itself is fragile — supporting 'Evolutionary Antifragile Therapy' as a strategy to prolong treatment sensitivity without changing cumulative dose.","limitations":"The study is primarily theoretical and preclinical (in vivo animal models); translation to human clinical trials has not been demonstrated. Sample sizes and specific cancer types/cell lines are not detailed in the abstract. The framework may not generalize to tumors with non-convex dose–response relationships.","practice_takeaway":"Clinicians should consider analyzing the dose–response curve shape (convex vs. concave) before designing dosing schedules — continuous dosing may suppress resistance better than intermittent high/low protocols when the dose–response is convex. This 'Evolutionary Antifragile Therapy' framework offers a principled, evolution-aware approach to sequencing targeted therapy without requiring higher cumulative doses."}},{"doi":"10.1097/cmr.0000000000001117","pmid":"42329709","title":"The role of circulating tumor DNA in the management of melanoma: a literature review","journal_title":"Melanoma Research","journal_issn":"0960-8931","published_at":"2026-06-23T00:00:00.000Z","url":"https://doi.org/10.1097/cmr.0000000000001117","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:18.447Z","updated_at":"2026-06-28T13:27:18.447Z","tags":[{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"modality","value":"Liquid Biopsy","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"study_design","value":"Literature Review","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"warning","value":"No sample size is reported, as this is a literature review aggregating multiple studies rather than a single cohort.","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"warning","value":"The full paper text was not accessible — only the abstract was available for extraction. All summary content is derived solely from the abstract. Specific study counts, individual trial data, and detailed methodology could not be verified.","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001117","tag_type":"warning","value":"The review does not describe a formal systematic search protocol; it may function more as a narrative review, which affects the level of evidence assigned.","value_numeric":null}],"summaries":{"what_studied":"This literature review evaluated the clinical utility of circulating tumor DNA (ctDNA) as a noninvasive biomarker across melanoma disease stages, examining biological mechanisms, detection methods, prognostic value, treatment monitoring, and residual disease assessment.","key_result":"Detectable baseline ctDNA was consistently linked to worse overall and progression-free survival (HRs ~2–3). In resected stage III melanoma, postoperative ctDNA positivity strongly predicted relapse (HRs approaching 10), with molecular recurrence often preceding clinical recurrence by months. Early ctDNA clearance during treatment correlated with radiographic response, while persistence indicated intrinsic resistance. Detection rates in early-stage disease were low (often <15%), limiting utility in that setting.","limitations":"The full text was not accessible — only the abstract was retrievable, so findings could not be verified against primary data tables or individual study details. The review does not report a systematic search methodology, raising potential selection bias. No pooled effect sizes or meta-analytic statistics are provided.","practice_takeaway":"In high-risk or advanced melanoma, serial ctDNA monitoring can flag emerging resistance mutations (NRAS, MEK1, PI3K-pathway) and predict relapse earlier than imaging — consider integrating it into post-resection surveillance for stage III disease. ctDNA adds limited value in early-stage, low-tumor-burden melanoma due to poor sensitivity (<15% detection)."}},{"doi":"10.1038/s41574-026-01271-8","pmid":"42315928","title":"From bench to bedside: the evolving role of iodine in thyroid cancer management","journal_title":"Nature Reviews Endocrinology","journal_issn":"1759-5029","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1038/s41574-026-01271-8","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-22T13:24:07.433Z","updated_at":"2026-06-22T13:24:07.433Z","tags":[{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"condition","value":"Differentiated Thyroid Carcinoma","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"condition","value":"Radioiodine-Refractory Thyroid Cancer","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"modality","value":"Radioactive Iodine Therapy","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"modality","value":"Redifferentiation Therapy","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"warning","value":"Age group tagged as 'adult' by convention for thyroid cancer reviews; the paper does not explicitly restrict its scope to adults.","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"warning","value":"No original clinical data or patient cohort is presented; all findings are synthesized from prior literature. Specific effect sizes and response rates for redifferentiation strategies are not directly reported in the abstract.","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01271-8","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the review's framing of molecular-guided redifferentiation as an emerging paradigm shift, but is not based on a single pivotal trial.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates the evolving role of iodine metabolism in differentiated thyroid carcinoma (DTC) management, covering iodide-handling mechanisms, molecular drivers of radioiodine-refractory (RAIR) disease, and redifferentiation strategies developed over the past 15 years.","key_result":"Molecular genetic profiling has been integrated into routine clinical practice; genetically guided redifferentiation strategies can restore radioiodine uptake in previously non-avid DTC lesions, offering new options for patients with RAIR advanced disease.","limitations":"As a narrative review, it does not provide pooled effect sizes or systematic evidence synthesis. No original patient data are presented, limiting direct clinical quantification of outcomes.","practice_takeaway":"Clinicians managing advanced DTC should incorporate molecular profiling to identify candidates for redifferentiation therapy before labeling disease as truly radioiodine-refractory. Emerging predictive biomarkers of RAIR status may refine patient stratification and inform sequencing of targeted therapies."}},{"doi":"10.1002/hed.70357","pmid":"42310965","title":"Current State and Future of Systemic Treatment for Elderly Patients With Head and Neck Cancer Undergoing Radiotherapy","journal_title":"Head & Neck","journal_issn":"1043-3074","published_at":"2026-06-17T00:00:00.000Z","url":"https://doi.org/10.1002/hed.70357","source_score":5,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:36.899Z","updated_at":"2026-06-27T13:27:36.899Z","tags":[{"paper_doi":"10.1002/hed.70357","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"generic","value":"carboplatin","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"generic","value":"cetuximab","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"modality","value":"Chemoradiotherapy","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"sample_size","value":"n=35","value_numeric":35},{"paper_doi":"10.1002/hed.70357","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"warning","value":"ICI efficacy findings are preliminary; the review flags the need for further research and biomarker identification before practice adoption.","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"warning","value":"Level of evidence is set to 3 (systematic review of heterogeneous, mostly non-RCT studies); the review explicitly notes study heterogeneity and limited trial representation of elderly patients, which may lower effective evidence quality.","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"warning","value":"The sample size tag reflects the number of included studies (n=35), not individual patients — total patient numbers are not reported in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This systematic review evaluated systemic treatment options — chemotherapy, targeted therapy, and immune checkpoint inhibitors (ICIs) — in patients aged 65+ with HNSCC receiving definitive or adjuvant radiotherapy, drawing from 35 included studies.","key_result":"Cisplatin-based CRT was the most effective and tolerable option for fit elderly patients. In unfit patients, cetuximab and carboplatin showed variable results. Adding ICIs to radiotherapy appeared feasible and safe, but efficacy data and predictive biomarkers remain insufficient.","limitations":"- Elderly patients are underrepresented in trials, limiting the evidence base.\n- Study heterogeneity across the 35 included studies makes direct comparisons difficult.\n- Evidence in the adjuvant setting is especially sparse.","practice_takeaway":"Use a comprehensive geriatric assessment — not age alone — to guide systemic therapy decisions in older HNSCC patients. Fit elderly patients can receive cisplatin-based CRT, but treatment should be individualized given the heterogeneity of available data."}},{"doi":"10.1080/17474124.2026.2671178","pmid":"42157509","title":"Adjuvant therapy in biliary tract tumors: how will immunotherapy fit in the future?","journal_title":"Expert Review of Gastroenterology & Hepatology","journal_issn":"1747-4124","published_at":"2026-06-11T00:00:00.000Z","url":"https://doi.org/10.1080/17474124.2026.2671178","source_score":13,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-26T13:25:27.929Z","updated_at":"2026-06-26T13:25:27.929Z","tags":[{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"condition","value":"Biliary Tract Cancer","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"condition","value":"Cholangiocarcinoma","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"warning","value":"Full text was not accessible; all structured content is derived from the abstract, article highlights, and publisher page only — specific trial names, patient numbers, and effect sizes referenced in the review body are not available.","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"warning","value":"No sample size tag applied as this is a review article with no primary patient cohort.","value_numeric":null},{"paper_doi":"10.1080/17474124.2026.2671178","tag_type":"warning","value":"Study design classified as 'Narrative Review' based on available metadata; the level of methodology rigor (e.g., systematic search strategy) cannot be confirmed without full text.","value_numeric":null}],"summaries":{"what_studied":"This narrative review covers adjuvant therapy trials for resected biliary tract cancers (cholangiocarcinoma and related tumors), summarizing completed and ongoing trials and exploring the potential role of immunotherapy, targeted therapies, and a shift toward perioperative (neoadjuvant) treatment strategies.","key_result":"Current adjuvant chemotherapy after surgery offers only marginal benefit with frequent relapses; the authors identify risk stratification, immunotherapy/targeted therapy intensification, and a move to perioperative treatment as the key levers to improve cure rates.","limitations":"Full text was not available — conclusions are drawn solely from the abstract and article highlights, limiting detail on specific trial data, patient populations, and effect sizes cited in the review.","practice_takeaway":"For resected biliary tract tumors, adjuvant capecitabine remains standard but is insufficient for many patients; clinicians should consider enrolling eligible patients in trials testing immunotherapy or targeted agents in the adjuvant or perioperative setting."}},{"doi":"10.1038/s41409-026-02914-0","pmid":"42237010","title":"Defining lines of therapy in haematological malignancies: a proposed systematic and comprehensive framework from the EBMT Practice Harmonisation and Guidelines Committee","journal_title":"Bone Marrow Transplantation","journal_issn":"0268-3369","published_at":"2026-06-03T00:00:00.000Z","url":"https://doi.org/10.1038/s41409-026-02914-0","source_score":13,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-11T13:42:51.118Z","updated_at":"2026-06-11T13:42:51.118Z","tags":[{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"condition","value":"Acute Leukemia","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"condition","value":"Hematological Malignancies","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"condition","value":"Lymphoma","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"modality","value":"Cellular Therapy","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"modality","value":"Hematopoietic Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"study_design","value":"Expert Consensus / Clinical Practice Guidelines","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"warning","value":"No sample size applies — this is a consensus framework, not a patient-level study.","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"warning","value":"Study design is expert consensus/guidelines; no empirical validation data are reported, so level of evidence is assigned as 5 (expert opinion).","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02914-0","tag_type":"warning","value":"The framework covers acute leukemias, lymphomas, and multiple myeloma but does not explicitly address all hematological malignancies (e.g., CLL, MDS); generalizability beyond the stated scope is unclear.","value_numeric":null}],"summaries":{"what_studied":"The EBMT Practice Harmonisation and Guidelines Committee developed a standardized framework for defining and recording 'lines of therapy' (LoT) across acute leukemias, lymphomas, and multiple myeloma, addressing wide variability in current practice.","key_result":"A LoT is defined as a coherent therapeutic episode aimed at achieving or maintaining disease control; a new LoT is triggered by progression, relapse, refractory disease, or introduction of an agent from a distinct therapeutic class — but not by dose adjustments, schedule changes, or toxicity-driven omissions. Bridging therapies before CAR-T or transplant are counted within the same LoT as the definitive treatment.","limitations":"This is a consensus framework document rather than an empirically validated study; real-world applicability and inter-rater reliability of the proposed definitions have not been tested prospectively.","practice_takeaway":"When documenting treatment history or enrolling patients in registries and trials, use this EBMT framework to assign LoT: count a new line only at progression/relapse/refractory disease or when a new therapeutic class is added, not at routine dose or schedule changes. Treat bridging therapy before CAR-T or stem cell transplant as part of the same LoT as the cellular therapy."}},{"doi":"10.1080/14737140.2026.2682866","pmid":"42216244","title":"Polypharmacy, polypharmacology, and polypharmacotherapy: clarifying definitions and complementary roles in cancer treatment – a narrative review","journal_title":"Expert Review of Anticancer Therapy","journal_issn":"1473-7140","published_at":"2026-06-02T00:00:00.000Z","url":"https://doi.org/10.1080/14737140.2026.2682866","source_score":2,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:38.436Z","updated_at":"2026-06-08T13:46:38.436Z","tags":[{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Cancer","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Chronic Myeloid Leukemia","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"HER2-Positive Breast Cancer","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"condition","value":"Renal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"modality","value":"Drug Repurposing","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"modality","value":"Multitarget-Directed Ligand","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"warning","value":"Full text was not available; summary is based on the abstract and article highlights only. Some details (e.g., specific drugs discussed, depth of evidence review) may not be fully captured.","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"warning","value":"No sample size tag applied — this is a review with no primary patient cohort.","value_numeric":null},{"paper_doi":"10.1080/14737140.2026.2682866","tag_type":"warning","value":"The 5.2% success rate and 2.8-month survival figures are cited from referenced external analyses, not generated by this review's own analysis.","value_numeric":null}],"summaries":{"what_studied":"This narrative review clarifies and distinguishes three concepts — polypharmacy, polypharmacology, and polypharmacotherapy — and examines their complementary roles in cancer treatment, with attention to drug repurposing and multitarget strategies as alternatives or adjuncts to precision oncology guided by the Somatic Mutation Theory (SMT).","key_result":"SMT-based precision oncology shows limited overall impact: a ~5.2% drug development success rate and a median overall survival benefit of only 2.8 months across 124 FDA-approved drugs (374 indications) from 2003–2021. The review argues polypharmacotherapy — using multiple repurposed non-oncology drugs targeting diverse pathways — offers a pragmatic, equitable complement to this approach.","limitations":"As a narrative (not systematic) review, it is subject to selection bias in the literature covered. No original clinical data are presented, and the efficacy of polypharmacotherapy remains to be validated in formal clinical trials, which the authors themselves identify as urgently needed.","practice_takeaway":"Clinicians should be aware that polypharmacy (multi-drug comorbidity management), polypharmacology (single multitarget drugs), and polypharmacotherapy (multi-drug cancer pathway targeting, often via repurposed agents) are distinct concepts with different risk-benefit profiles. Repurposed non-oncology drugs used in combination represent a low-cost, potentially more equitable strategy worth considering in trial design, especially for patients with limited access to targeted therapies."}},{"doi":"10.1136/jitc-2025-012427","pmid":"42086309","title":"Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma","journal_title":"Journal for ImmunoTherapy of Cancer","journal_issn":"2051-1426","published_at":"2026-05-06T00:00:00.000Z","url":"https://doi.org/10.1136/jitc-2025-012427","source_score":44,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-05","doi":"10.1136/jitc-2025-012427","days":"14","issn":"2051-1426","rank":"5","field":"Clinical Medicine","score":"44","category":"Immunology","categories":["Immunology"],"_categories":["Immunology"]},"pubmed":{"doi":"10.1136/jitc-2025-012427","title":"Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma.","journal":"Journal for immunotherapy of cancer","methods":"","results":"Outlier splicing analysis identified 10 aberrant splice events specific to mRCC. AS analysis revealed 461 differentially spliced events between responders and non-responders in the ICI cohort and 253 in the targeted therapy cohort, with intron retention as the predominant motif. Thirteen unique AS events were enriched in responders, including ","abstract":"$30","keywords":["Biomarker","Immune Checkpoint Inhibitor","Renal Cell Carcinoma","Tumor microenvironment - TME"],"pubmed_id":"42086309","conclusions":"","publication_date":"2026-05-06T00:00:00"},"crossref":{"DOI":"10.1136/jitc-2025-012427","URL":"https://doi.org/10.1136/jitc-2025-012427","ISSN":["2051-1426"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1136/jitc-2025-012427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"e012427","type":"journal-article","issue":"5","score":1,"title":["Characterization of aberrant alternative splicing landscape in patients with metastatic renal cell carcinoma"],"author":[{"given":"Ameish","family":"Govindarajan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, 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No single trial result is reported; this is a guideline synthesis.","limitations":"As a narrative/evidence-based guideline review rather than a primary study, it does not report original data, sample sizes, or direct comparisons. The scope of Part I is not fully delineated from Part II, limiting assessment of completeness.","practice_takeaway":"Clinicians managing endometrial cancer should incorporate molecular classification into staging and treatment planning, consistent with updated SGO guidance. Awareness of expanded maintenance and targeted therapy options is essential, given rising incidence and mortality trends."}},{"doi":"10.1182/blood.2026033049","pmid":"41915766","title":"Consensus recommendations for malignant histiocytic neoplasms (histiocytic, Langerhans, and interdigitating dendritic cell sarcomas)","journal_title":"Blood","journal_issn":"0006-4971","published_at":"2026-03-31T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2026033049","source_score":18,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-20T13:36:07.570Z","updated_at":"2026-07-20T13:36:07.570Z","tags":[{"paper_doi":"10.1182/blood.2026033049","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"condition","value":"Histiocytic Sarcoma","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"condition","value":"Interdigitating Dendritic Cell Sarcoma","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"condition","value":"Langerhans Cell Sarcoma","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"condition","value":"Malignant Histiocytic Neoplasms","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"modality","value":"Immune Checkpoint Inhibition","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"modality","value":"Surgical Resection","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"study_design","value":"Consensus Guidelines / Expert Recommendations","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"warning","value":"Level of evidence is expert consensus (Delphi process); no randomized or prospective trial data underpin the treatment algorithms.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"warning","value":"No sample size is reported — this is a consensus statement, not a clinical trial with enrolled patients.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"warning","value":"Sex distribution of the underlying patient population referenced in case reviews is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033049","tag_type":"warning","value":"The study_design label 'Consensus Guidelines' is used as no standard RCT/cohort design applies; clinicians should interpret recommendations accordingly.","value_numeric":null}],"summaries":{"what_studied":"An international Histiocyte Society working group used a modified Delphi process and case-based review to develop consensus recommendations for malignant histiocytic neoplasms (MHNs) — including histiocytic sarcoma, Langerhans cell sarcoma, and interdigitating dendritic cell sarcoma — covering classification, diagnostics, molecular testing, and treatment.","key_result":"Over 40 consensus statements were produced. Key outputs include: adoption of a unified 'MHN' designation, a minimum immunophenotypic panel, broad molecular profiling integration, and tiered treatment algorithms favoring surgical resection for unifocal disease and targeted therapy or immune checkpoint inhibition (based on actionable mutations or PD-L1 expression) for multifocal disease.","limitations":"Recommendations are expert-consensus based (modified Delphi), not derived from prospective trials — reflecting the rarity of MHNs and absence of randomized data. No formal evidence grading is reported, and the consensus process may not capture all mixed or ambiguous phenotypes.","practice_takeaway":"For unifocal MHN, prioritize surgical resection; for multifocal disease, pursue broad molecular profiling and PD-L1 testing to guide targeted therapy or checkpoint inhibitor selection. Always document prior hematopoietic malignancy, as it affects lineage interpretation and management."}},{"doi":"10.1182/bloodadvances.2021006469","pmid":"41670627","title":"American Society of Hematology 2026 guidelines for frontline management of acute lymphoblastic leukemia in adolescents and young adults","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-02-11T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2021006469","source_score":107,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-03T13:38:59.555Z","updated_at":"2026-07-03T13:38:59.555Z","tags":[{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"age_group","value":"adolescent","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"condition","value":"Acute Lymphoblastic Leukemia","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"modality","value":"Allogeneic Hematopoietic Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"modality","value":"Asparaginase-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"study_design","value":"Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"warning","value":"Critical: The embedded PDF full text is not the guideline document — it is a U.S. Census Bureau bar chart on uninsured rates by age group (2020–2021). All structured content is derived exclusively from the abstract. Individual recommendation grades, GRADE certainty levels, subgroup-specific data, and good practice statements are not available for extraction.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"warning","value":"Publication date listed as 2026-02-11, but DOI references 'bloodadvances.2021006469' — the submission/manuscript ID may reflect an earlier draft year. Verify final publication details.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2021006469","tag_type":"warning","value":"Sample size tag omitted: no patient-level N is reported in a guideline document of this type.","value_numeric":null}],"summaries":{"what_studied":"ASH 2026 evidence-based guidelines for frontline management of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs), covering regimen selection, transplantation, and targeted agents, based on systematic evidence review through November 2023.","key_result":"The panel issued 15 recommendations: pediatric-inspired, asparaginase-containing regimens are preferred over adult-inspired protocols; allogeneic HSCT is not routinely recommended in first remission (reserved for higher-risk subsets or suboptimal responders); and frontline use of targeted agents is increasingly supported.","limitations":"The full text of the paper could not be extracted — the PDF metadata corresponds to a U.S. Census Bureau figure on uninsured rates, not the guideline document itself. Summary is based solely on the abstract. Specific recommendation grades, GRADE certainty levels, and supporting data for individual recommendations are unavailable.","practice_takeaway":"For AYA patients with ALL, use a pediatric-inspired regimen containing asparaginase as frontline therapy rather than traditional adult protocols. Reserve allogeneic HSCT for first remission only in higher-risk patients or those with suboptimal initial responses."}},{"doi":"10.1080/0886022x.2025.2590283","pmid":"41290561","title":"Anticancer drug-induced nephrotoxicity: biopsy-proven patterns and outcomes across chemotherapy, targeted therapy, and immune checkpoint inhibitors","journal_title":"Renal Failure","journal_issn":"0886-022X","published_at":"2025-11-26T00:00:00.000Z","url":"https://doi.org/10.1080/0886022x.2025.2590283","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-11-30","doi":"10.1080/0886022x.2025.2590283","days":"7","issn":"0886-022X","rank":"8","field":"Clinical Medicine","score":"7","category":"Urology & Nephrology","categories":["Urology & Nephrology"],"_categories":["Urology & Nephrology"]},"pubmed":{"doi":"10.1080/0886022X.2025.2590283","title":"Anticancer drug-induced nephrotoxicity: biopsy-proven patterns and outcomes across chemotherapy, targeted therapy, and immune checkpoint inhibitors.","journal":"Renal failure","methods":"","results":"","abstract":"Biopsy-confirmed anticancer drug-induced kidney injury is underreported. 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Outcomes were first‑year per‑capita health care and systemic therapy costs, time toxicity within 1 year of initial treatment, and overall survival.","key_result":"Mean first‑year health care costs were higher in 2018–2019 vs 2007–2012 ($47,886 vs $33,347), with larger increases in stage III ($67,108 vs $46,511) and stage IV ($117,450 vs $47,739). Systemic therapy costs rose across stages (stage II $40,823 vs $10,309; stage III $55,699 vs $9,764; stage IV $79,358 vs $9,318); 3‑year OS improved (74.2% vs 65.8%; HR 0.72, 95% CI 0.61–0.85; P<.001); time toxicity was similar, though stage IV patients averaged 58.7 vs 44.2 days with health system contact (>1 day/week; standardized difference 0.40; P=.20).","limitations":"Retrospective, propensity score–matched comparison of different eras (2007–2012 vs 2018–2019). Costs and time toxicity were measured only in the first year and within a single provincial health system.","practice_takeaway":"Adoption of immunotherapy and targeted therapy for stage II–IV melanoma was linked with higher first‑year costs and substantial time burden for stage IV patients, alongside better 3‑year survival. Discuss these trade‑offs when planning systemic therapy."}}],"initialOffset":17,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Targeted Therapy"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Targeted Therapy"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Targeted Therapy"}}}]]

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