{"publication_id":"db433f84-030f-4867-807f-8b21fe4b1673","content_hash":"sha256:5b461a0ca2ffde54d7d9282566c0b574387153b4da1fa6b66135569b35f0981c","nodes":[{"id":"db433f84-030f-4867-807f-8b21fe4b1673","type":"publication","title":"Adjacent Evidence Brief: Cancer Rates — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 29/39 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This synthesis tests the thesis that evidence for Cancer Rates is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Cancer in older adults is increasingly framed not only by incidence and mortality but by intersecting risks of frailty, cardiometabolic comorbidity, and treatment-related morbidity, motivating structured evidence syntheses that can keep mechanism, indirect human data, and direct clinical endpoints separate. We performed an AI-assisted structured evidence synthesis with full audit trail across 39 curated references spanning RCTs, observational cohorts, and systematic reviews, prespecified by outcome class (frailty, longevity, cardiometabolic, immune inflammation, contextual other) and by directness of evidence."},{"id":"claim_2","type":"claim","text":"Evidence-honesty note: 29/39 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_3","type":"claim","text":"This synthesis tests the thesis that evidence for Cancer Rates is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation."},{"id":"claim_4","type":"claim","text":"Cancer in older adults is increasingly framed not only by incidence and mortality but by intersecting risks of frailty, cardiometabolic comorbidity, and treatment-related morbidity, motivating structured evidence syntheses that can keep mechanism, indirect human data, and direct clinical endpoints separate."},{"id":"claim_5","type":"claim","text":"We performed an AI-assisted structured evidence synthesis with full audit trail across 39 curated references spanning RCTs, observational cohorts, and systematic reviews, prespecified by outcome class (frailty, longevity, cardiometabolic, immune inflammation, contextual other) and by directness of evidence."},{"id":"claim_6","type":"claim","text":"Across the corpus, the Cancer evidence base supports a context-dependent profile: frailty and selected cardiometabolic and chemoprevention exposures carry consistent negative or harmful signals, while direct exercise and several inflammation-modifying interventions show positive effects on intermediate endpoints, but the boundary conditions under which mechanistic and indirect biomarker effects translate into hard-outcome benefit in older adults with cancer remain inadequately defined."},{"id":"claim_7","type":"claim","text":"Evidence-abstraction note.** The 39 retained reference papers are not 39 independent primary clinical trials: 29 are review, indirect, mechanistic, or registered-protocol source-level summaries, and 10 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence."},{"id":"claim_8","type":"claim","text":"Within the retained source corpus for cancer rates, among adults, do findings for contextual adjacent evidence and cardiometabolic support a decision-grade conclusion (clinically actionable where applicable), and which population, study-design, and directness boundaries keep extrapolation to other outcome classes hypothesis-generating?"},{"id":"claim_9","type":"claim","text":"Population aging confronts health systems with an unusual arithmetic: gains in life expectancy have not produced equivalent gains in years free of chronic disease, and the residual years spent with disability, frailty, and incident cancer dominate late-life burden. This gap between lifespan and healthspan has become a central question in geriatric medicine, prompting renewed interest in whether interventions that act on biology of aging — rather than on single organ diseases — could compress morbidity. Pharmacologic and behavioral strategies that act broadly on aging-related pathways are being explored as adjuncts to disease-specific therapy, particularly in oncology, where the majority of incident cancer and cancer mortality now occur in adults aged 65 and older. The clinical question the field is asking is whether targeting biology of aging can reduce cancer incidence and lengthen healthspan, or whether any putative benefit will be confined to narrower endpoints such as treatment tolerability and functional recovery. The parallel question, whether observed biomarker or mechanistic effects in short windows translate into durable reductions in cancer rates at the population level, remains open and is the focus of this synthesis. Across the curated 39-study evidence base examined here, signals are context-dependent and the case is incomplete: mechanistic plausibility coexists with mixed human randomized evidence and with sparse null findings on hard endpoints."},{"id":"claim_10","type":"claim","text":"The geroscience hypothesis offers a unifying logic for studying such interventions: if multiple chronic diseases of aging share upstream mechanisms (chronic inflammation, cellular senescence, mitochondrial dysfunction, altered proteostasis), then a single intervention that modulates those mechanisms might yield parallel benefits across endpoints. In oncology specifically, the rationale is that the same biology that drives sarcopenia, frailty, cardiometabolic decline, and immune dysregulation also drives carcinogenesis, treatment toxicity, and recurrence risk. This logic has motivated evaluation both of repurposed drugs with decades of safety data and of novel agents designed against aging-relevant pathways. Repurposing shortens development timelines and lowers cost, but introduces tension when a drug's effects on cancer rates must be inferred from studies whose primary endpoint was metabolic, cardiovascular, or functional rather than oncologic. Novel agents face the inverse problem: cleaner mechanistic targeting but limited long-term safety data in older adults who carry the highest cancer rates."},{"id":"claim_11","type":"claim","text":"Cancer is a critical outcome class in this literature for three converging reasons. First, given its age-related incidence, any intervention that meaningfully lengthens healthspan in older adults should, in principle, be detectable in cancer rates, either as primary prevention or as a downstream consequence of improved resilience. Second, the available randomized trials in older cancer patients — spanning exercise (Zopf 2026), anti-inflammatory adjuvant therapy (Zhang 2026, Gwenzi 2026), perioperative geriatric assessment (Matsuoka 2026), and multimodal prehabilitation (Pecorelli 2026) — collectively enroll frail, sarcopenic, or multimorbid populations that overlap with the demographic bearing the highest cancer burden. Third, observational cohorts enriched for frail and sarcopenic adults (Sahin 2026, Lee 2026, Li 2026b) and for older surgical candidates (Fujimoto 2025) offer indirect windows onto whether biology-of-aging interventions are doing what proponents hope. The Cancer question therefore sits at the intersection of geriatric oncology, cardio-oncology, and geroscience — a position that yields unusually rich but methodologically heterogeneous evidence. [bundle:1] [bundle:3] [bundle:10] [bundle:12] [bundle:13] [bundle:17] [bundle:20] [bundle:29] [bundle:37]"},{"id":"claim_12","type":"claim","text":"Important unresolved questions structure the field. Whether a favorable effect on a mechanistic biomarker (e. For example, reduced inflammatory cytokine burden, preserved skeletal muscle mass) translates into a measurable reduction in cancer rates is the central question, and one for which surrogate-endpoint caution, as discussed by Ioannidis 2005, applies directly. Tradeoffs between competing outcomes — for example, the cancer-related mortality signal reported in long-term aspirin follow-up (Orchard 2026) and cardiometabolic benefits seen in statin cohort work (Huang 2026) — suggest that the same intervention may move hard endpoints in opposite directions. Population specificity matters: effects in frail older adults undergoing cancer surgery (Sahin 2026) may not generalize to community-dwelling breast cancer survivors participating in exercise trials (Asencio-Mas 2026, Ruiz-Campos 2026). The question of whether null findings on contextual or functional outcomes (Galavotti 2026, Rajamaki 2026, Carlos 2026) reflect true absence of effect or underpowered subgroup analyses in older patients remains contested. [bundle:3] [bundle:11] [bundle:14] [bundle:19] [bundle:23] [bundle:24] [bundle:38] [bundle:39]"},{"id":"claim_13","type":"claim","text":"This synthesis contributes a structured weighting of an unusually heterogeneous evidence base, organized to separate mechanistic surrogate evidence from clinical hard-outcome evidence and to keep direct (A1 / D1) and indirect evidence streams in distinct lanes. By mapping the cross-study disagreements surfaced across outcome classes — for instance, parallel null findings in contextual outcome work (Peker 2026 vs Cui 2026 vs RamirezGiraldo 2026 vs Galavotti 2026), and the partial conflict between frailty-negative and frailty-null sources (Jin 2026 vs Normann 2026, Jin 2026 vs Marginean 2026) — the analysis aims to clarify where the evidence base supports clinical claims about cancer rates and where it does not. Positively framed findings in immune inflammation contrast with negative signals in longevity (Sahin 2026) and frailty (Jin 2026, Lee 2026) and with null findings dominating contextual other and certain longevity outcomes (Rajamaki 2026, Carlos 2026, Orchard 2026 partial). The result is a deliberately conservative map of what is currently known about the effects of biology-of-aging interventions on cancer rates, framed as questions the field continues to ask rather than conclusions about clinical efficacy — a positioning intended to make the boundary conditions for future trials, and the methodological standards those trials will need to meet, explicit. [bundle:1] [bundle:3] [bundle:4] [bundle:19] [bundle:21] [bundle:23] [bundle:27] [bundle:33] [bundle:35] [bundle:36] [bundle:38] [bundle:39]"},{"id":"claim_14","type":"claim","text":"The background evidence for cancer rates is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Zopf 2026, Gwenzi 2026, Hu 2025 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation. [bundle:10] [bundle:17] [bundle:18]"},{"id":"claim_15","type":"claim","text":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect."},{"id":"claim_16","type":"claim","text":"Across the retained sources, positive signals cluster around the immune and inflammation outcome class; null signals around the contextual adjacent evidence, longevity and frailty outcome classes; and negative or adverse signals around the longevity, frailty and muscle function outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation."},{"id":"claim_17","type":"claim","text":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty."},{"id":"claim_18","type":"claim","text":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support."},{"id":"claim_19","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_20","type":"claim","text":"A source was coded as direct only when it tested the topic itself against a clinically proximate outcome in the relevant population. Human evidence with an adjacent exposure, population, or outcome was coded as indirect; syntheses and secondary reviews were coded as review-level evidence and were not counted as direct sources."},{"id":"claim_21","type":"claim","text":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification."},{"id":"claim_22","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, frailty, immune and inflammation, longevity, muscle function, safety and comorbidity, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_23","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_24","type":"claim","text":"| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |"},{"id":"claim_25","type":"claim","text":"| Cardiometabolic | Fujimoto 2025: Impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing cancer surgery: A single‐center retrospective cohort study | direction=unclear | directness=indirect | B2 | outcome=Cardiometabolic; direction=unclear | finding=representative non-significant statistic P = 0.651; not treated as positive or negative directional support unless source direction is coded | [bundle:12]"},{"id":"claim_26","type":"claim","text":"| Cardiometabolic | Li 2026a: Cancer and the risk of death, heart-failure hospitalization, and major adverse cardiovascular events in HFpEF: a propensity-matched cohort study | direction=mixed | directness=indirect | B2 | outcome=Cardiometabolic; direction=mixed | finding=representative statistic P = 0.031; source-level statistic reported | [bundle:2]"},{"id":"claim_27","type":"claim","text":"| Cardiometabolic | Torres 2025: Long-Term Effectiveness of Dietary Interventions on Inflammatory Biomarkers in Women with Breast Cancer: A Systematic Review and Meta-Analysis | direction=null | directness=review | B1 | outcome=Biomarker/Adjacent Cardiometabolic; direction=null | finding=representative non-significant statistic P = 0.653; not treated as positive or negative directional support unless source direction is coded | [bundle:5]"},{"id":"claim_28","type":"claim","text":"| Contextual Adjacent Evidence | Anker 2025: Heart failure therapy in patients with advanced cancer receiving specialized palliative care (EMPATICC trial) | direction=unclear | directness=indirect | B2 | outcome=Contextual Adjacent Evidence; direction=unclear | finding=representative non-significant statistic P = 0.83; not treated as positive or negative directional support unless source direction is coded | [bundle:7]"},{"id":"claim_29","type":"claim","text":"| Contextual Adjacent Evidence | Asencio-Mas 2026: Effects of Diet and Exercise Lifestyle Interventions on Physical and Psychological Health in Breast Cancer Survivors: A Systematic Review | direction=unclear | directness=review | B2 | outcome=Contextual Adjacent Evidence; direction=unclear | finding=representative statistic P = 0.008; source-level statistic reported | [bundle:11]"},{"id":"claim_30","type":"claim","text":"| Contextual Adjacent Evidence | Burgos-Bragado 2026: Asynchronous telerehabilitation in prehabilitation and postoperative recovery for colorectal cancer: A protocol for a randomized controlled trial | direction=null | directness=direct | A1 | outcome=Contextual Adjacent Evidence; direction=null | finding=7 extracted claim(s); source-level direction is the coded finding | [bundle:34]"},{"id":"source_1","type":"source","study":"Long-term outcomes in elderly colorectal cancer patients with presarcopenia: a single center retrospective cohort study","year":2026,"doi":"10.1186/s12877-026-06995-w","url":"https://doi.org/10.1186/s12877-026-06995-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Lee 2026","quote":"The presarcopenia group was older than the normal group ( p = 0.02), with a lower body mass index ( p < 0.001). Preoperative blood test results indicated a higher frequency of anemia ( p = 0.002), hypoalbuminemia ( p = 0.009), and a higher neutrophil-to-lymphocyte ratio ( p = 0.012) in the presarcopenia group.","evidence_span":"| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |","excerpt":"BACKGROUND: Insufficient evidence exists regarding the characteristics of elderly patients with presarcopenia and their prognosis. Therefore, we aim to investigate the impact of preoperative presarcopenia on postoperative outcomes in elderly patients with resectable colorectal cancer. METHODS: We included patients aged ≥ 75 years who underwent curative resection between June 2009 and December 2019. The psoas muscle index was calculated based on the computed tomography scan at the L3 level (lumbar area). The primary outcome was the difference in overall survival based on the presence or absence of presarcopenia. The secondary outcomes included differences in the occurrence of postoperative complications, tumor recurrence, and the impact of adjuvant chemotherapy on survival rates in high-risk stage II cancer. RESULTS: We included 325 patients (presarcopenia: 63) in this study. The presarcopenia group was older than the normal group (p = 0.02), with a lower body mass index (p < 0.001). Preoperative blood test results indicated a higher frequency of anemia (p = 0.002), hypoalbuminemia (p = 0.009), and a higher neutrophil-to-lymphocyte ratio (p = 0.012) in the presarcopenia group."},{"id":"source_2","type":"source","study":"Cancer and the risk of death, heart-failure hospitalization, and major adverse cardiovascular events in HFpEF: a propensity-matched cohort study","year":2026,"doi":"10.3389/fonc.2026.1728009","url":"https://doi.org/10.3389/fonc.2026.1728009","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Li 2026a","quote":"Of 403 eligible patients (cancer, 174; non-cancer, 229; median follow-up, 36 months), PSM yielded 306 patients (153 per group) with excellent covariate balance. In the matched cohort, cumulative incidences at 48 months were higher with cancer than without for all-cause mortality (31.4% vs .","evidence_span":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","excerpt":"BACKGROUND: Cancer and heart failure with preserved ejection fraction (HFpEF) frequently coexist in older adults and may share pathobiology, yet the independent effect of cancer on clinical outcomes in HFpEF remains uncertain. METHODS: We performed a single-center, retrospective cohort study using electronic health records from January 2020 through December 2024. Adults with HFpEF were stratified by a history of biopsy-proven or imaging-confirmed cancer. Primary outcomes were all-cause mortality, heart-failure hospitalization (HFH), and a composite of major adverse cardiovascular events (MACE: nonfatal myocardial infarction, HF rehospitalization, or arrhythmia requiring intervention). Secondary outcomes included change in New York Heart Association (NYHA) class, health status by Kansas City Cardiomyopathy Questionnaire (KCCQ), cause-specific mortality, and HFpEF-related health-care utilization. Propensity-score matching (PSM; 1:1 nearest-neighbor, caliper 0.2) balanced key covariates (age, sex, comorbidities, renal function, biomarkers, NYHA class, and LVEF)."},{"id":"source_3","type":"source","study":"Can the frailty score independently predict postoperative morbidity in patients with colorectal cancer? A prospective observational study","year":2026,"doi":"10.1186/s12877-026-07255-7","url":"https://doi.org/10.1186/s12877-026-07255-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sahin 2026","quote":"Thirty-day postoperative complications occurred in 40 patients (20%), and 30-day mortality was 5% (10/200). In multivariable models, EFS remained independently associated with complications (OR 1.284; p = 0.006) and mortality (OR 1.323; p = 0.014).","evidence_span":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","excerpt":"BACKGROUND: Frailty is associated with adverse surgical outcomes in older adults. We evaluated whether the Edmonton Frail Scale (EFS) is independently associated with 30-day postoperative morbidity and mortality after major colorectal cancer surgery. METHODS: This prospective observational study enrolled patients aged ≥ 65 years undergoing elective oncologic colorectal resection (March–September 2025). Patients were stratified into five EFS frailty categories. The primary outcomes were 30-day postoperative complications (Clavien–Dindo; Grade I–II vs Grade III–V) and 30-day all-cause mortality. Associations were assessed using ROC analysis and multivariable logistic regression. RESULTS: Of 205 enrolled patients, 200 were analyzed (63% male; median age 70 years). Thirty-day postoperative complications occurred in 40 patients (20%), and 30-day mortality was 5% (10/200). EFS was associated with longer hospital length of stay and higher complication and mortality rates. EFS showed excellent discrimination for postoperative complications (AUC 0.928; 95% CI 0.886–0.970), with an optimal cut-off of ~ 6.5 (sensitivity 96.2%, specificity 76.9%)."},{"id":"source_4","type":"source","study":"Impact of pre-operative frailty on short-term outcomes of ovarian cancer: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s13048-026-01982-6","url":"https://doi.org/10.1186/s13048-026-01982-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Jin 2026","quote":"Meta-analysis showed that the presence of frailty was associated with a statistically significant increase in the risk of all complications (OR: 1.61 95% CI: 1.35, 1.92 I 2 = 44%) and major complications (OR: 1.80 95% CI: 1.31, 2.47 I 2 = 54%) in patients with ovarian cancer. Meta-analysis showed that the presence of frailty did not significantly increase the risk of minor complications (OR: 1.39 95% CI: 0.93, 2.07 I 2 = 0%) or mortality (OR: 1.12 95% CI: 0.59, 2.12 I 2 = 0%) in patients with ovarian cancer.","evidence_span":"| Cancer Rates / Contextual Adjacent Evidence | n=16; claims=533 | significant source statistic in 7/16 sources; receipt-level direction coded null | 7 direct; 5 indirect; 4 review | limited corpus depth in this outcome class |","excerpt":"OBJECTIVE: Frailty has been linked to adverse outcomes after numerous surgical procedures; however, its utility for ovarian cancer patients undergoing surgery remains undefined. We systematically reviewed literature to examine the risk of short-term adverse events in surgically treated ovarian cancer patients based on the presence of frailty. METHODS: Web of Science, Embase, PubMed and Scopus databases were searched for all observational studies published from the inception of the databases to 14 August 2025. Data on all complications, major complications, minor complications, mortality and readmission were pooled in a random effects model. RESULTS: Eleven studies were included. Meta-analysis showed that the presence of frailty was associated with a statistically significant increase in the risk of all complications (OR: 1.61 95% CI: 1.35, 1.92 I2 = 44%) and major complications (OR: 1.80 95% CI: 1.31, 2.47 I2 = 54%) in patients with ovarian cancer. Meta-analysis showed that the presence of frailty did not significantly increase the risk of minor complications (OR: 1.39 95% CI: 0.93, 2.07 I2 = 0%) or mortality (OR: 1.12 95% CI: 0.59, 2.12 I2 = 0%) in patients with ovarian cancer."},{"id":"source_5","type":"source","study":"Long-Term Effectiveness of Dietary Interventions on Inflammatory Biomarkers in Women with Breast Cancer: A Systematic Review and Meta-Analysis","year":2025,"doi":"10.1093/nutrit/nuaf137","url":"https://doi.org/10.1093/nutrit/nuaf137","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Torres 2025","quote":"Adherence to a healthy diet significantly decreased C-reactive protein (CRP) levels compared with the control group (standard mean difference = -0.17; 95% CI -0.32 to -0.02; I 2 = 0.00%). This result was maintained in the interventions focused on weight loss, including only patients with overweight, those incorporating physical activity, when follow-up was restricted to 6 months, and with interventions lasting at least 6 months.","evidence_span":"| Cancer Rates / Cardiometabolic | n=5; claims=534 | mixed signal in 2/5 sources | 3 indirect; 2 review | limited corpus depth in this outcome class |","excerpt":"CONTEXT: Improving the prognosis of breast cancer remains a challenge despite the reduction in its mortality rates. Inflammatory parameters have been suggested as prognostic biomarkers of cancer. A healthy diet could potentially modify these factors; however, to date, findings have been inconclusive. OBJECTIVE: This review was conducted to estimate the strength of the association between healthy dietary interventions and inflammatory markers in women with breast cancer after a minimum 6-month follow-up. DATA SOURCES: The following literature databases were searched: MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library. DATA EXTRACTION: Clinical trials that compared the effect of dietary interventions on the inflammatory profile of patients with breast cancer were selected. Quality was assessed using the Cochrane Collaboration risk-of-bias tool. Two researchers independently selected and evaluated the quality of the studies based on eligibility criteria. DATA ANALYSIS: Mean differences between intervention groups and their 95% CIs were calculated using a random-effects model. The presence of heterogeneity was analyzed with Cochran's Q test, and I2 was estimated."},{"id":"source_6","type":"source","study":"A phase IV prospective study of efficacy and safety of ribociclib and letrozole as first-line therapy in older women (≥70 years) with hormone receptor-positive HER2-negative advanced breast cancer: the RibOB study","year":2026,"doi":"10.1016/j.esmoop.2025.105896","url":"https://doi.org/10.1016/j.esmoop.2025.105896","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Houdt 2026","quote":"The RibOB study was an open-label, single-arm phase IV prospective trial evaluating first-line ribociclib 600 mg 3 weeks out of 4 with letrozole in women ≥70 years with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Median overall survival rate was not reached and breast cancer-specific survival rate at 24 and 36 months was 82% and 75%, respectively.","evidence_span":"| Cancer Rates / Longevity | n=5; claims=220 | significant source statistic in 1/5 sources; receipt-level direction coded unclear | 2 indirect; 3 review | limited corpus depth in this outcome class |","excerpt":"BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors with endocrine therapy are standard first-line therapy for patients with hormone receptor-positive metastatic breast cancer. Older patients, especially the frailer subpopulation, are underrepresented in clinical trials, limiting data on treatment and safety outcomes in this population. PATIENTS AND METHODS: The RibOB study was an open-label, single-arm phase IV prospective trial evaluating first-line ribociclib 600 mg 3 weeks out of 4 with letrozole in women ≥70 years with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, functional evolution and quality of life (QoL), and outcomes in relation to clinical frailty assessed by G8. RESULTS: Seventy patients were enrolled: median age 76 years, with 30% ≥80 years. Forty-five out of 70 patients had a G8 score of ≤14 (frail) at baseline. With a median follow-up of 30.5 months, the median PFS was 36 months (95% confidence interval 24 months-not estimable)."},{"id":"source_7","type":"source","study":"Heart failure therapy in patients with advanced cancer receiving specialized palliative care (EMPATICC trial)","year":2025,"doi":"10.1093/eurheartj/ehaf705","url":"https://doi.org/10.1093/eurheartj/ehaf705","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Anker 2025","quote":"The primary endpoint did not differ between groups (win ratio 0.95, 95% confidence interval [CI] 0.57-1.58; P = .83). Overall, mortality was 32% at 30 days (not different between groups).","evidence_span":"| Cancer Rates / Frailty | n=4; claims=177 | significant source statistic in 2/4 sources; receipt-level direction coded null | 3 indirect; 1 review | limited corpus depth in this outcome class |","excerpt":"BACKGROUND AND AIMS: Advanced cancer may resemble a heart failure (HF)-like phenotype marked by cardiac wasting, dyspnoea, congestion, and/or physical dysfunction. The trial evaluated safety and efficacy of HF therapy among patients with advanced cancer receiving specialized palliative care to improve patients' self-care ability. METHODS: Patients with stage 4 solid tumours with a life expectancy of 1-6 months receiving specialized palliative care were enrolled. Patients were required to meet at least two cardiovascular risk criteria and at least one criterion for functional limitation. Participants were randomized 1:1 to receive optimized HF therapy (up to four drugs: sacubitril/valsartan, empagliflozin, ivabradine, ferric carboxymaltose) or placebo in a double-blind setting. The primary hierarchical endpoint included: (i) days alive and able to wash oneself, (ii) ability to walk 4 m, and (iii) self-reported patient global assessment (PGA) of subjective well-being, during the 30-day placebo-controlled phase. RESULTS: In five centres, 93 patients were randomized. The primary endpoint did not differ between groups (win ratio 0.95, 95% confidence interval [CI] 0.57-1.58; P = .83)."},{"id":"source_8","type":"source","study":"Change in skeletal muscle mass during systemic cancer treatment: a systematic review and meta-analysis","year":2026,"doi":"10.2340/1651-226X.2026.45726","url":"https://doi.org/10.2340/1651-226X.2026.45726","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Svendsen 2026","quote":"In a multicohort study including patients with advanced non-small cell lung cancer ( n = 1,791), less SMM decline was associated with a 26-54% lower mortality risk (Hazard Ratio [HR]: 0.46-0.74) [ 20 ]. Similarly, SMM loss during treatment was associated with poorer overall survival as in colorectal ( n = 67; ≥ 9% SMM loss, HR: 4.47, 95% confidence interval [CI]: 2.21-9.05) [ 21 ], biliary tract ( n = 524; SMM loss; HR: 2.58, 95% CI: 1.86-3.58) [ 22 ] and pancreatic cancer ( n = 127; ≥ 7.9% SMM loss; HR: 4.02, 95% CI: 1.87-8.97) [ 23 ].","evidence_span":"| Cancer Rates / Immune and Inflammation | n=3; claims=156 | significant source statistic in 2/3 sources; receipt-level direction coded unclear | 2 direct; 1 protocol | limited corpus depth in this outcome class |","excerpt":"BACKGROUND AND PURPOSE: Loss of skeletal muscle mass (SMM) is common during systemic cancer treatment, but the magnitude and variability across cancer and treatment types remain uncertain. We aimed to describe changes in SMM during systemic cancer treatment supported by pooled quantitative estimates. PATIENTS/MATERIAL AND METHODS: We systematically searched PubMed, Embase, and Web of Science until April 2025 for longitudinal studies reporting SMM during chemotherapy and/or immunotherapy (± targeted therapy) in patients with cancer (PROSPERO CRD42022308388). Standardized mean changes (SMC) were pooled in random-effects meta-analyses using the restricted maximum-likelihood estimator with Hartung-Knapp adjustment. Heterogeneity was assessed using I². Risk of bias was assessed with the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Seventy-eight studies (n = 10,502; 52% male; median age 64 years [interquartile range, IQR: 34-77]) were included. Meta-analysis across cancers showed an association between systemic cancer treatment and decline in SMM (59 studies; n = 6,373; SMC = -0.24, 95% confidence interval [CI]: -0.29 to -0."},{"id":"source_9","type":"source","study":"In-bedroom renewed air as anti-inflammatory adjuvant therapy in cancer survivors: protocol for the randomised, placebo-controlled BREATHS N-of-1 trial series","year":2026,"doi":"10.1136/bmjopen-2025-111748","url":"https://doi.org/10.1136/bmjopen-2025-111748","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"protocol","cited_as":"Hernandez-Garcia 2026","quote":"Eligible participants are aged ≥18 years with a history of breast, colorectal, prostate, lung or haematological cancer, prior cardiotoxic cancer therapy and CRP ≥3 mg/L. Sequence duration ranges from 4 weeks to 12 weeks, depending on whether a clinically meaningful CRP reduction (<2 mg/L or ≥35% relative to placebo) is achieved during active treatment of each cycle.","evidence_span":"| Cancer Rates / Muscle Function | n=2; claims=147 | significant source statistic in 1/2 sources; receipt-level direction coded unclear | 1 direct; 1 review | limited corpus depth in this outcome class |","excerpt":"INTRODUCTION: Inflammation is causally related to cancer progression and cardiovascular toxicities of anticancer treatments. Fine particulate matter (PM 2.5 ) air filtration lowers interleukin-6 and C reactive protein (CRP) levels in high-risk cardiopulmonary groups, though potential synergistic or confounding effects with routine medications-statins, cyclo-oxygenase-2 inhibitors, beta-blockers-remain poorly understood. Whether overnight in-bedroom PM 2.5 air filtration effectively reduces inflammation and prothrombotic biomarkers in survivors of adult-onset cancer at high cardiovascular toxicity risk is unknown. METHODS AND ANALYSIS: BREATHS is a series of randomised, adaptive, blinded, placebo-controlled N-of-1 trials conducted in densely populated urban areas of Valencia, Spain, during winter when PM 2.5 concentrations historically exceed WHO guidelines. Eligible participants are aged ≥18 years with a history of breast, colorectal, prostate, lung or haematological cancer, prior cardiotoxic cancer therapy and CRP ≥3 mg/L."},{"id":"source_10","type":"source","study":"Exercise effects on lean body mass, muscle strength and functional performance in patients with metastatic breast cancer: the randomized controlled PREFERABLE-EFFECT study","year":2026,"doi":"10.1186/s13058-026-02235-6","url":"https://doi.org/10.1186/s13058-026-02235-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Zopf 2026","quote":"Patients with mBC (n = 357) were randomized to a 9-month supervised aerobic, resistance and balance exercise program (EX) or control. Body composition (subset n = 66), lower body strength (subset n = 126), handgrip strength and functional performance were assessed at baseline, 3 and 6 months.","evidence_span":"Evidence-honesty note: 29/39 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","excerpt":"BACKGROUND: Low skeletal muscle mass and strength are common in patients with metastatic breast cancer (mBC) and have been associated with treatment toxicities and poor prognosis. The PREFERABLE-EFFECT study (NCT04120298) investigated exercise effects on body composition, muscle strength, and functional performance (secondary outcomes) in patients with mBC. METHODS: Patients with mBC (n = 357) were randomized to a 9-month supervised aerobic, resistance and balance exercise program (EX) or control. Body composition (subset n = 66), lower body strength (subset n = 126), handgrip strength and functional performance were assessed at baseline, 3 and 6 months. Changes between groups were compared using linear mixed models for repeated measures. RESULTS: EX significantly increased whole body lean mass at 3 months (between-group difference = 0.79 kg, 95%CI [0.14; 1.44], effect size = 0.14), appendicular skeletal muscle mass at 3 months (0.60 kg, [0.22; 0.97], ES = 0.19) and 6 months (0.48kg, [0.09; 0.87], ES = 0.15), and lower body strength at 3 months (18.32 kg, [7.58; 29.06], ES = 0.44) and 6 months (34.22 kg, [23.0; 45.45], ES = 0.83) compared to control."},{"id":"source_11","type":"source","study":"Effects of Diet and Exercise Lifestyle Interventions on Physical and Psychological Health in Breast Cancer Survivors: A Systematic Review","year":2026,"doi":"10.3390/nu18111815","url":"https://doi.org/10.3390/nu18111815","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Asencio-Mas 2026","quote":"Effects were larger in multimodal supervised programs combining caloric restriction with moderate-to-vigorous aerobic plus resistance training (5-8% weight loss; 19-29% visceral fat reduction; improved insulin, IGF-1, leptin, adiponectin and EORTC QLQ-C30 scores), whereas digital or low-intensity interventions produced smaller, less uniform objective effects despite improving dietary behaviors. Of these, 30 were excluded because they were not relevant to the study: studies on diseases other than breast cancer ( n = 10), books or book chapters ( n = 2), and studies that did not meet the inclusion criteria ( n = 18).","evidence_span":"| Cancer Rates / Safety and Comorbidity | n=2; claims=109 | significant source statistic in 1/2 sources; receipt-level direction coded unclear | 1 indirect; 1 review | limited corpus depth in this outcome class |","excerpt":"Breast cancer survivors frequently experience adverse changes in body composition, cardiometabolic biomarkers, functional capacity and quality of life that may worsen long-term prognosis, yet the comparative effectiveness of lifestyle interventions across delivery formats and supervision levels remains unclear. Background/Objectives: This systematic review assessed the effects of structured diet and exercise interventions on body composition, metabolic and inflammatory biomarkers, functional capacity, dietary habits and quality of life in breast cancer survivors. Methods: Following PRISMA guidelines, Cochrane, PubMed, Scopus and Web of Science were searched for randomized controlled trials and quasi-experimental studies published in English between 2016 and 2026. Risk of bias was assessed with RoB 2 and ROBINS-I and certainty of evidence with GRADE. Results: Of 1413 records, 15 studies (11 RCTs; mean age 46-60 years; mostly overweight or obese post-treatment women) met the inclusion criteria; twelve interventions were supervised and three home-based or web-based."},{"id":"source_12","type":"source","study":"Impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing cancer surgery: A single‐center retrospective cohort study","year":2025,"doi":"10.1111/jdi.70224","url":"https://doi.org/10.1111/jdi.70224","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fujimoto 2025","quote":"This single‐center retrospective cohort study included 1,063 older patients ≥65 years who underwent preoperative evaluation for gastrointestinal cancer between 2012 and 2019. Compared with the non‐DM group, the DM group had higher body mass index (21.5 vs 22.6 kg/m 2 ), higher cardiovascular disease prevalence (26.9 vs 41.2%), and more frequent weak grip strength (53.9 vs 65.8%).","evidence_span":"| Cancer Rates / Dosing and Pharmacokinetics | n=1; claims=29 | significant source statistic in 1/1 sources; receipt-level direction coded unclear | 1 indirect | single-source slice; hypothesis-generating |","excerpt":"AIMS/INTRODUCTION: Diabetes mellitus (DM) increases postoperative risks and may worsen physical function through muscle loss. Patients undergoing malignancies surgery are aging, and age-related declines in physical function, particularly sarcopenia, also adversely affects outcomes. As DM and physical decline are interrelated, we aimed to examine how they impact outcomes in older patients undergoing gastrointestinal cancer surgery. MATERIALS AND METHODS: This single-center retrospective cohort study included 1,063 older patients ≥65 years who underwent preoperative evaluation for gastrointestinal cancer between 2012 and 2019. We stratified patients based on current DM and physical function assessed by grip strength. The main outcome was postoperative survival. Cox proportional hazards models examined associated factors. RESULTS: After exclusions, 655 without DM (non-DM group) and 257 patients with DM (DM group) were analyzed (mean age: 79.1 ± 4.1 years, 66.8% male). Compared with the non-DM group, the DM group had higher body mass index (21.5 vs 22.6 kg/m 2 ), higher cardiovascular disease prevalence (26.9 vs 41.2%), and more frequent weak grip strength (53.9 vs 65.8%)."},{"id":"source_13","type":"source","study":"Impact of Preoperative Frailty on Postoperative Complications and Cognitive Impairment in Liver Cancer Patients: An Observational Cohort Study","year":2026,"doi":"10.2147/CIA.S589717","url":"https://doi.org/10.2147/CIA.S589717","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Li 2026b","quote":"Frailty status was assessed using the Fried Phenotype criteria on 1 day before surgery, and cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) on postoperative day 3. A total of 43 patients (37.4%) developed postoperative complications, which may have been associated with preoperative frailty and its components, including exhaustion, grip strength, and low physical activity.","evidence_span":"| Cancer Rates / Skeletal, Fracture, and Bone | n=1; claims=13 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |","excerpt":"BACKGROUND: Frailty is characterized by an age-related decline in physiological reserve and is closely linked to postoperative outcomes. Early identification of preoperative frailty is therefore essential. This study aims to examine the associations between preoperative frailty and postoperative complications and cognitive impairment in patients with liver cancer, and to identify potential contributing factors. METHODS: This observational cohort study was conducted at the Affiliated Hospital of Jiangnan University from February to June 2025 and included 115 patients with liver cancer who underwent surgery. Frailty status was assessed using the Fried Phenotype criteria on 1 day before surgery, and cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) on postoperative day 3. Postoperative complications occurring before discharge were also recorded. RESULTS: A total of 43 patients (37.4%) developed postoperative complications, which may have been associated with preoperative frailty and its components, including exhaustion, grip strength, and low physical activity."},{"id":"source_14","type":"source","study":"Grading the evidence on the effects of exercise interventions in children and adolescents during and beyond cancer treatment: an umbrella review of systematic reviews with meta-analyses","year":2026,"doi":"10.1136/bjsports-2025-110756","url":"https://doi.org/10.1136/bjsports-2025-110756","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Ruiz-Campos 2026","quote":"Systematic reviews with meta-analysis of controlled trials (randomised or non-randomised) evaluating exercise interventions in children and adolescents (≤19 years) during and beyond cancer treatment. Attending to the most comprehensive meta-analyses, exercise induced significant benefits on cardiorespiratory fitness (mean difference (MD) 6.92% (95% CI 1.01% to 12.82%)), cognitive function (standardised mean difference (SMD) 0.26 (95% CI 0.08 to 0.44)) and cognitive performance (SMD 0.41 (95% CI 0.17 to 0.65)), with moderate certainty of evidence.","evidence_span":"Contextual Adjacent Evidence: n=16; claims=533; no extracted directional signal in 8/16 sources | directness: 7 direct; 5 indirect; 4 review; main limitation: directionally heterogeneous.","excerpt":"OBJECTIVE: To synthesise the evidence on the effects of exercise interventions in children and adolescents during and beyond cancer treatment, and to evaluate the methodological quality and certainty of this evidence. DESIGN: Umbrella review of systematic reviews with meta-analyses. DATA SOURCE: PubMed, Web of Science, Scopus, SPORTDiscus and CINAHL were searched from inception to January 2026. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analysis of controlled trials (randomised or non-randomised) evaluating exercise interventions in children and adolescents (≤19 years) during and beyond cancer treatment. Reviews without quantitative synthesis, those including only observational studies, or interventions where the isolated effect of exercise could not be determined were excluded. RESULTS: 19 systematic reviews with meta-analyses, including 53 primary studies (n=2361 participants), were identified, yielding 80 effect estimates. Attending to the most comprehensive meta-analyses, exercise induced significant benefits on cardiorespiratory fitness (mean difference (MD) 6.92% (95% CI 1.01% to 12.82%)), cognitive function (standardised mean difference (SMD) 0."},{"id":"source_15","type":"source","study":"Association between malnutrition and prognosis in colorectal cancer: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fonc.2026.1789366","url":"https://doi.org/10.3389/fonc.2026.1789366","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Gao 2026","quote":"Pooled hazard ratios (HRs), risk ratios (RRs), and mean differences (MDs) with 95% confidence intervals (CIs) were synthesized using random-effects models. It was also associated with increased postoperative infectious complications (RR 1.61, 95% CI 1.51-1.98; I² = 0.0%), major complications (RR 1.36, 95% CI 1.18-1.60), overall postoperative complications (RR 1.44, 95% CI 1.25-1.56), 30-day mortality (RR 2.03, 95% CI 1.35-3.31), and 30-day readmission (RR 1.34, 95% CI 1.01-1.64).","evidence_span":"Cardiometabolic: n=5; claims=534; mixed signal in 2/5 sources | directness: 3 indirect; 2 review; main limitation: no direct clinical anchor.","excerpt":"BACKGROUND: Malnutrition is prevalent in colorectal cancer (CRC) and may adversely influence oncologic prognosis and perioperative recovery. This systematic review and meta-analysis quantified associations between malnutrition diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria and clinical outcomes in CRC. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Embase, Web of Science Core Collection, and The Cochrane Library were searched through December 31, 2025. Observational cohort studies enrolling adults with CRC and reporting outcomes according to GLIM-defined malnutrition were included. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled hazard ratios (HRs), risk ratios (RRs), and mean differences (MDs) with 95% confidence intervals (CIs) were synthesized using random-effects models. RESULTS: Nine cohort studies involving 4,771 patients were included. GLIM-defined malnutrition was associated with poorer overall survival (HR 1.23, 95% CI 1.12-1.33; I² = 56.4%). It was also associated with increased postoperative infectious complications (RR 1.61, 95% CI 1.51-1."},{"id":"source_16","type":"source","study":"Long-Term Outcomes of Concurrent Chemoradiotherapy With S-1 in Older Patients With Esophageal Cancer","year":2026,"doi":"10.1001/jamanetworkopen.2026.3541","url":"https://doi.org/10.1001/jamanetworkopen.2026.3541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Ji 2026","quote":"Esophageal cancer (EC) ranks as the seventh leading cause of cancer-related mortality worldwide, with approximately 40% of cases diagnosed in patients 70 years or older. 14 The regimen was well tolerated, with grade 3 or higher adverse events (AEs) occurring in less than 10% of patients.","evidence_span":"Longevity: n=5; claims=220; no extracted directional signal in 2/5 sources | directness: 2 indirect; 3 review; main limitation: no direct clinical anchor.","excerpt":"IMPORTANCE: Most older patients with esophageal cancer (EC) are unable to complete standard platinum-based concurrent chemoradiotherapy (CCRT) due to reduced organ reserve, comorbidities, and malnutrition. A new treatment option-CCRT with S-1-has been found to have high efficacy and fewer toxic effects for this population, yet long-term data supporting its use remain limited. OBJECTIVE: To evaluate the long-term outcomes of CCRT with S-1 vs radiotherapy (RT) alone in older patients with EC. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a phase 3 randomized clinical trial conducted at 23 centers in China was not prespecified in the trial protocol. Patients aged 70 to 85 years with histologically confirmed EC were enrolled between June 1, 2016, and August 31, 2018. Data cutoff date was February 1, 2025, with an additional follow-up of 54 months beyond the primary analysis. Data were analyzed from February 1 to April 1, 2025. INTERVENTIONS: Patients were randomly assigned 1:1 to receive CCRT with S-1 consisting of 54 Gy in 30 fractions with S-1, 70 mg/m2 per day on days 1 to 14 and 29 to 42, or RT alone consisting of 60 Gy in 30 fractions, 2."},{"id":"source_17","type":"source","study":"Effects of personalized vitamin D 3 on inflammation in colorectal cancer patients: a randomized trial","year":2026,"doi":"10.1038/s41416-025-03333-6","url":"https://doi.org/10.1038/s41416-025-03333-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Gwenzi 2026","quote":"In an ongoing randomized double-blind, placebo-controlled trial in Germany, CRC patients who underwent surgery in the past year and had serum 25-hydroxyvitamin D levels < 60 nmol/L were randomly assigned to either a personalized loading dose of VIDS, followed by a maintenance dose of 2000 IU/day or a placebo for 12 weeks. The VIDS group exhibited 39.3% reduction in IL-6 levels compared to the placebo group (95% CI: -54.9% to -18.2%; p = 0.001).","evidence_span":"This synthesis tests the thesis that evidence for Cancer Rates is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.","excerpt":"BACKGROUND: Low vitamin D status and inflammation are associated with poor prognosis among colorectal cancer (CRC) patients. We assessed the efficacy of personalized vitamin D 3 supplementation (VIDS) for reducing inflammation in patients with low vitamin D status. METHODS: In an ongoing randomized double-blind, placebo-controlled trial in Germany, CRC patients who underwent surgery in the past year and had serum 25-hydroxyvitamin D levels < 60 nmol/L were randomly assigned to either a personalized loading dose of VIDS, followed by a maintenance dose of 2000 IU/day or a placebo for 12 weeks. Changes in serum interleukin-6 (IL-6), interferon-gamma (IFN-γ), and matrix metalloproteinase (MMP-1) were compared at the end of trial among 126 patients (65 in the placebo and 61 in the intervention group). RESULTS: The VIDS group exhibited 39.3% reduction in IL-6 levels compared to the placebo group (95% CI: -54.9% to -18.2%; p = 0.001). The reductions observed in IFN-γ and MMP-1 due to VIDS were not statistically significant (-6.7%; p = 0.69 and -5.4%; p = 0.23, respectively)."},{"id":"source_18","type":"source","study":"Lobaplatin versus cisplatin in concurrent chemoradiotherapy for elderly cervical cancer: randomized controlled phase II study","year":2025,"doi":"10.3802/jgo.2026.37.e33","url":"https://doi.org/10.3802/jgo.2026.37.e33","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Hu 2025","quote":"Elderly cervical cancer patients aged ≥65 years were randomly assigned (1:1) to lobaplatin-based (2 cycles of lobaplatin 30 mg/m 2 every 3 weeks) or cisplatin-based (5 cycles of cisplatin 40 mg/m 2 every week) CCRT. The lobaplatin group showed higher chemotherapy completion rates compared to the cisplatin group (83.9% vs.","evidence_span":"Cancer in older adults is increasingly framed not only by incidence and mortality but by intersecting risks of frailty, cardiometabolic comorbidity, and treatment-related morbidity, motivating structured evidence syntheses that can keep mechanism, indirect human data, and direct clinical endpoints separate.","excerpt":"OBJECTIVE: This phase II study compared the efficacy and safety of lobaplatin vs. cisplatin in concurrent chemoradiotherapy (CCRT) for elderly cervical cancer patients. METHODS: Elderly cervical cancer patients aged ≥65 years were randomly assigned (1:1) to lobaplatin-based (2 cycles of lobaplatin 30 mg/m² every 3 weeks) or cisplatin-based (5 cycles of cisplatin 40 mg/m² every week) CCRT. Radiotherapy included external beam radiotherapy (50.4 Gy in 28 fractions) and intracavitary brachytherapy (30 Gy in 5 fractions). RESULTS: From January 1, 2020, to December 31, 2023, 64 patients were enrolled: 31 were randomly assigned to the lobaplatin group and 33 to the cisplatin group. The lobaplatin group showed higher chemotherapy completion rates compared to the cisplatin group (83.9% vs. 54.5%, p=0.011). The objective response rate and disease control rate were comparable between 2 groups (93.5% vs. 93.9%, 96.8% vs. 97.0%). The 1- and 2-year overall survival rates of the lobaplatin group and the cisplatin group were 96.0% vs. 96.6%, 90.7% vs. 96.6%, respectively (p=0.558). The lobaplatin group had a lower incidence of nephrotoxicity (39.4% vs. 9.7%, p=0."},{"id":"source_19","type":"source","study":"Age, Age‐Related Comorbidities and Survival in Palbociclib, Ribociclib and Abemaciclib Users With Advanced Breast Cancer: A Nation‐Wide Retrospective Cohort Study","year":2026,"doi":"10.1002/pds.70416","url":"https://doi.org/10.1002/pds.70416","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Rajamaki 2026","quote":"The prevalence of age or frailty‐related comorbidities in individuals ≥ 65 years was low, highest for cardiovascular diseases, 32.3%, and diabetes, 16.9%. The median survival was 25.3 months, with longer median survival times in younger age groups (27.7 months in < 65 year‐olds, 25.1 months in aged 65-74, 21.4 months in aged 75-84 years, and 15.4 months in 85 years or older).","evidence_span":"Frailty: n=4; claims=177; no extracted directional signal in 2/4 sources | directness: 3 indirect; 1 review; main limitation: no direct clinical anchor.","excerpt":"PURPOSE: Prevalence of breast cancer (BC) increases with age, but the external validity of data obtained from pivotal trials of medicinal products remains a concern due to the underrepresentation of frail and older adults. Cyclin-dependent kinase inhibitors (CDKi), palbociclib, abemaciclib, and ribociclib are considered an essential part of the standard-of-care in the management of advanced/metastatic breast cancer. We investigated age, comorbidities, and survival in a nationwide real-world cohort of CDKi users. METHODS: Data from the Finnish Cancer Registry, reimbursed dispensed prescriptions, Electronic Prescription Database, Care Register for Health Care (CRHC), and Causes of Death Register were combined and analysed. RESULTS: Altogether 1921 women with BC initiated CDKi treatment in 2018-2022. The median age at initiation was 66.9 years, with 43.2% of the study cohort being < 65 years of age, 36.1% 65-74 years, 19.0% 75-84 years, and 1.7% 85 years or older. The prevalence of age or frailty-related comorbidities in individuals ≥ 65 years was low, highest for cardiovascular diseases, 32.3%, and diabetes, 16.9%. The median survival was 25."},{"id":"source_20","type":"source","study":"Intravenous lidocaine reduces systemic inflammation but not myocardial injury following thoracic surgery for lung cancer: a randomized controlled trial","year":2026,"doi":"10.1186/s12871-026-03733-y","url":"https://doi.org/10.1186/s12871-026-03733-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Zhang 2026","quote":"Dosing was adjusted to ideal body weight for BMI ≥ 25 kg m - ². Between June 12, 2021, and June 12, 2022, we enrolled 119 patients who underwent thoracic surgery for lung cancer (mean age 59.41 years [SD 11.085], 58 [48.7%] male).","evidence_span":"We performed an AI-assisted structured evidence synthesis with full audit trail across 39 curated references spanning RCTs, observational cohorts, and systematic reviews, prespecified by outcome class (frailty, longevity, cardiometabolic, immune inflammation, contextual other) and by directness of evidence.","excerpt":"BACKGROUND: Elevated high-sensitivity troponin T levels shortly after noncardiac surgery are closely linked to myocardial injury, a key factor in 30-day postoperative mortality. Intravenous lidocaine, known for its potent anti-inflammatory and membrane-stabilizing properties, has shown cardioprotective potential in other surgical settings, but its efficacy in noncardiac thoracic surgery remains unclear. OBJECTIVES: This study was a double-blind, placebo-controlled randomized trial. Participants were randomly allocated to the lidocaine or placebo group with a 1:1 ratio. DESIGN: Single-centre, double-blind, randomized controlled trial. SETTING: Academic tertiary care medical centre. PATIENTS: Patients scheduled for noncardiac thoracic surgery, predominantly via video-assisted thoracoscopic surgery (VATS), under general anesthesia from June 12, 2021 to June 12, 2022. INTERVENTIONS: Patients received intravenous lidocaine (1.5 mg kg− 1 bolus pre-induction followed by 1.5 mg kg− 1 h− 1 infusion until surgery end) or volume-matched saline. Dosing was adjusted to ideal body weight for BMI ≥ 25 kg m−². Study drugs were prepared by blinded staff and administered via standardized pumps."},{"id":"source_21","type":"source","study":"Impact of Age on Surgical and Oncologic Outcomes After Colorectal Cancer Resection in Selected Patients Undergoing Primary Anastomosis: A Retrospective Propensity‐Matched Cohort Study","year":2026,"doi":"10.1002/cam4.71927","url":"https://doi.org/10.1002/cam4.71927","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"RamirezGiraldo 2026","quote":"8.8%; p = 0.252), or 30‐day perioperative mortality (3.7% vs. 0.7%; p = 0.216), although perioperative mortality was numerically higher among patients aged ≥ 75 years.","evidence_span":"Immune and Inflammation: n=3; claims=156; mixed signal in 2/3 sources | directness: 2 direct; 1 protocol; main limitation: directionally heterogeneous.","excerpt":"BACKGROUND: The impact of age on perioperative morbidity and long-term oncologic outcomes in colorectal cancer remains controversial. Although aging is linked to greater comorbidity and functional decline, advances in perioperative care have challenged the idea that older patients have worse outcomes. This study evaluated surgical and oncologic results in patients aged ≥ 75 years compared with younger individuals. METHODS: We conducted a retrospective cohort study including patients who underwent colorectal resection with primary anastomosis between 2015 and 2022. Patients were grouped by age (< 75 vs. ≥ 75 years) and matched 1:1 using propensity scores based on preoperative clinical and tumor-related variables. Major complications (Clavien-Dindo grade ≥ III) were analyzed using logistic regression, and OS and RFS were assessed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 651 eligible patients, 272 were included in the matched cohort. No statistically significant differences were found between age groups in hospital stay (4.5 vs. 4.0 days; p = 0.270), reintervention (13.2% vs. 8.8%; p = 0.333), major complications (14.0% vs. 8.8%; p = 0."},{"id":"source_22","type":"source","study":"Esketamine-sufentanil PCA reduces postoperative depression state in elderly colorectal cancer patients: a randomized controlled trial","year":2026,"doi":"10.1038/s41598-026-49287-4","url":"https://doi.org/10.1038/s41598-026-49287-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Ding 2026","quote":"This double-blind RCT enrolled 99 elderly (≥ 65 years) CRC resection patients, randomized to three postoperative PCA groups: C: Sufentanil (2 µg/kg) + saline placebo, ES1: Sufentanil + esketamine 1 mg/kg, ES2: Sufentanil + esketamine 2 mg/kg. Depression/Anxiety: Both esketamine groups showed significantly lower HAMD/HAMA scores vs. control at 24 h and 72 h (e.g., 24 h HAMD: ES1 6.16 ± 2.16, ES2 7.10 ± 2.55 vs.","evidence_span":"Across the corpus, the Cancer evidence base supports a context-dependent profile: frailty and selected cardiometabolic and chemoprevention exposures carry consistent negative or harmful signals, while direct exercise and several inflammation-modifying interventions show positive effects on intermediate endpoints, but the boundary conditions under which mechanistic and indirect biomarker effects translate into hard-outcome benefit in older adults with cancer remain inadequately defined.","excerpt":"Elderly colorectal cancer (CRC) patients face high risks of postoperative depression state, inadequately addressed by opioid-based analgesia. Esketamine, an NMDA receptor antagonist with rapid antidepressant effects, offers potential benefits but lacks evidence in this population. This double-blind RCT enrolled 99 elderly (≥ 65 years) CRC resection patients, randomized to three postoperative PCA groups: C: Sufentanil (2 µg/kg) + saline placebo, ES1: Sufentanil + esketamine 1 mg/kg, ES2: Sufentanil + esketamine 2 mg/kg. Primary outcomes were anxiety/depression (HAMA/HAMD scores) at 24 h postoperatively. Secondary outcomes included VAS pain scores, patient satisfaction, and adverse events. Depression/Anxiety: Both esketamine groups showed significantly lower HAMD/HAMA scores vs. control at 24 h and 72 h (e.g., 24 h HAMD: ES1 6.16 ± 2.16, ES2 7.10 ± 2.55 vs. C 9.87 ± 3.67; p < 0.001), with no dose-dependent difference (p > 0.05 ES1 vs. ES2). Pain Control: No intergroup differences in resting/activity VAS scores or rescue analgesia demands (p > 0.05). Satisfaction: Higher satisfaction rates in ES1 (77.4%) and ES2 (90.0%) vs. C (50.0%) (p = 0.002)."},{"id":"source_23","type":"source","study":"Integrating Exercise and Education into Lung Cancer Care: Results from the OVER-CRF Pilot Study on Cancer-Related Fatigue and Quality of Life","year":2026,"doi":"10.3390/curroncol33060313","url":"https://doi.org/10.3390/curroncol33060313","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Galavotti 2026","quote":"In Europe, it accounts for an estimated 11% of all cancer diagnoses, corresponding to 314,857 new cases in 2024 [ 2 ]. Indeed, CRF is one of the most prevalent and debilitating symptoms experienced by individuals with lung cancer, affecting up to 80% of survivors [ 5 , 6 ].","evidence_span":"Muscle Function: n=2; claims=147; mixed signal in 1/2 sources | directness: 1 direct; 1 review; main limitation: directionally heterogeneous.","excerpt":"Background: Cancer-Related Fatigue (CRF) significantly impairs physical performance and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC). The OVER-CRF study evaluated the feasibility, safety, and preliminary efficacy of a personalized pulmonary rehabilitation (PR) program combining supervised exercise and education during active treatment. Methods: Patients with stage II-III NSCLC were randomized to Early-PR (initiated at the start of anticancer therapy) or Delayed-PR (initiated three months later). The 3-month intervention included two educational sessions and eight supervised exercise sessions. The primary outcome was adherence; secondary outcomes included safety, CRF (FACIT-FS), QoL (EORTC-QLQ-C30), and physical performance (6MWT). Results: Thirty-one patients were randomized (mean age 67.4 years). Adherence was excellent (Early: 86.7%; Delayed: 91.7%), exceeding feasibility thresholds. No exercise-related adverse events occurred. At 12 months, 50% of participants showed clinically meaningful CRF improvements."},{"id":"source_24","type":"source","study":"Dose–response effect of statins on colorectal cancer risk in IBD: a nationwide cohort study","year":2026,"doi":"10.1186/s12885-026-15970-y","url":"https://doi.org/10.1186/s12885-026-15970-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Huang 2026","quote":"Statin use also correlated with lower all-cause mortality (aHR 0.42; 95% CI, 0.35-0.51). We included adults aged ≥ 20 years with newly diagnosed inflammatory bowel disease (IBD) between January 1, 2008, and December 31, 2019, with follow-up through December 31, 2022.","evidence_span":"These sources are not strictly contradictory because they interrogate different exposures (cancer history versus dietary intervention) and different endpoints (in-hospital mortality/bleeding versus inflammatory biomarkers), but they jointly illustrate that the cardiometabolic domain is heterogeneous rather than uniformly adverse. Together, these disagreements argue that a single composite cardiometabolic label is insufficient, and the boundary conditions of population, exposure, and endpoint must be specified before the cancer–cardiometabolic relationship can be characterized quantitatively.","excerpt":"BACKGROUND: Patients with inflammatory bowel disease (IBD) face an elevated risk of colorectal cancer (CRC). Statins have demonstrated potential anticancer properties, but evidence in IBD populations remains limited. OBJECTIVE: To evaluate the association between sustained statin use and the risk of CRC in patients with IBD, and to assess dose–response relationships and statin type-specific effects. DESIGN: Nationwide, retrospective cohort study using time-dependent Cox proportional hazards models and Fine–Gray competing risk models. RESULTS: Among 6,120 propensity score–matched adults with IBD (2,040 statin users and 4,080 non-statin lipid-lowering agent users), statin use was associated with a 65% reduction in CRC risk compared with users of non-statin lipid-lowering agents (adjusted hazard ratio [aHR] 0.35; 95% CI, 0.24–0.52; p<0.0001). A clear dose–response relationship was observed, with the highest quartile of cumulative exposure associated with an aHR of 0.08. Rosuvastatin and simvastatin conferred the strongest protective effects. Statin use also correlated with lower all-cause mortality (aHR 0.42; 95% CI, 0.35–0.51)."},{"id":"source_25","type":"source","study":"Efficacy and safety of neoadjuvant therapies for high-risk and locally advanced prostate cancer in older adults: a systematic review and network meta-analysis","year":2026,"doi":"10.3389/fonc.2026.1796138","url":"https://doi.org/10.3389/fonc.2026.1796138","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Yuan 2026","quote":"Epidemiological data demonstrated a sharp rise in incidence with advancing age, peaking between 65-69 years, while mortality peaks later at 70-74 years before declining ( 2 , 3 ). Patients were aged 55 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (on a scale ranging from 0 to 5, with higher scores indicating greater disability).","evidence_span":"The contextual evidence base for Cancer in aging adults spans a heterogeneous set of trials and cohort studies whose primary endpoints sit outside the core incidence/mortality axis but inform interpretation of disease burden. Across these direct-RCT designs the dose schedules and follow-up windows differ, but each enrolled a clinically defined older cancer population.","excerpt":"BACKGROUND: Brief overview of high-risk/locally advanced prostate cancer in older adults, current neoadjuvant therapies (NHT, NNHT, NCHT), and the uncertainty regarding their comparative efficacy on pathological outcomes. OBJECTIVES: This study aims to compare the efficacy and safety profiles of various neoadjuvant treatments in improving pathological outcomes-including positive surgical margin (PSM) rates, minimal residual disease (MRD), clinical downstaging, and post-treatment prostate-specific antigen (PSA) reduction-in older adults with high-risk or locally advanced prostate cancer. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science for relevant randomized controlled trials and prospective comparative studies published from January 2010 to April 20, 2025. The primary pathological outcomes were positive surgical margin (PSM) rate and minimal residual disease (MRD). Secondary outcomes included clinical downstaging and prostate-specific antigen (PSA) response. All network meta-analyses were performed using Bayesian frameworks, with treatment ranking evaluated via the surface under the cumulative ranking curve (SUCRA)."},{"id":"source_26","type":"source","study":"Effect of yoga on musculoskeletal complaints in women during endocrine treatment for breast cancer: protocol of the randomised controlled COBRA trial","year":2026,"doi":"10.1136/bmjopen-2026-117251","url":"https://doi.org/10.1136/bmjopen-2026-117251","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Veenhuizen 2026","quote":"Approximately 40% of women stop endocrine therapy for hormone-receptor-positive breast cancer within the first 5 years of prescribed treatment because of side effects. The waitlist control group is asked to maintain their habitual lifestyle during the first 18 weeks and will participate in a similar yoga programme to the intervention group for the following 18 weeks.","evidence_span":"Evidence-abstraction note.** The 39 retained reference papers are not 39 independent primary clinical trials: 29 are review, indirect, mechanistic, or registered-protocol source-level summaries, and 10 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.","excerpt":"INTRODUCTION: Approximately 40% of women stop endocrine therapy for hormone-receptor-positive breast cancer within the first 5 years of prescribed treatment because of side effects. Musculoskeletal complaints are among the most frequently reported side effects. The Cancer Of the BReast Asanas (COBRA) study examines the effect of an 18-week yoga programme on endocrine therapy-associated musculoskeletal complaints in women with breast cancer. METHODS AND ANALYSIS: In total, 140 women will be randomised in a 1:1 ratio to the intervention or waitlist control group. The intervention programme consists of two times a week 1-hour supervised Hatha or (easy) Vinyasa yoga classes at a yoga or sports centre for 18 weeks and once per week a half-hour at home using videos. The waitlist control group is asked to maintain their habitual lifestyle during the first 18 weeks and will participate in a similar yoga programme to the intervention group for the following 18 weeks. The control group yoga programme is offered live-remote."},{"id":"source_27","type":"source","study":"Impact of prognostic nutritional index and geriatric nutritional risk index on prognosis in elderly patients with early-stage prostate cancer","year":2026,"doi":"10.3389/fnut.2026.1745718","url":"https://doi.org/10.3389/fnut.2026.1745718","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peker 2026","quote":"This single-center retrospective cohort study included 205 patients aged ≥65 years with early-stage prostate cancer treated between 2018 and 2024. Low GNRI was linked to a median survival of 74 months.","evidence_span":"Quantitative findings from the surgical and supportive-care literature further populate the contextual outcome space.","excerpt":"AIM: Prostate cancer predominantly affects older men and generally has a favorable early-stage prognosis, yet the prognostic significance of nutritional and inflammatory status remains uncertain. This study evaluated the prognostic value of the Prognostic Nutritional Index (PNI) and Geriatric Nutritional Risk Index (GNRI) in elderly patients with localized prostate cancer. METHODS: This single-center retrospective cohort study included 205 patients aged ≥65 years with early-stage prostate cancer treated between 2018 and 2024. Nutritional status was assessed at baseline using serum albumin, lymphocyte count, and body weight to calculate the PNI and GNRI. Overall survival was analyzed using standard survival analysis methods. All statistical analyses were performed using SPSS software version 26.0. RESULTS: The median patient age was 72 years. Of all patients, 41% were 75 years or older. Survival analysis showed that patients with low PNI had a median OS of 78 months. Those with high PNI had a median OS of 115 months ( p = 0.008). Low GNRI was linked to a median survival of 74 months. High GNRI was linked to 120 months ( p = 0.009)."},{"id":"source_28","type":"source","study":"In-hospital outcomes of acute coronary syndrome in patients with cancer: a systematic review and meta-analysis.","year":2026,"doi":"10.2459/jcm.0000000000001894","url":"https://doi.org/10.2459/jcm.0000000000001894","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Ahmad 2026","quote":"Cancer history increased all-cause mortality by 44% [RR: 1.44; 95% confidence interval (CI): 1.21-1.71; P < 0.001], bleeding by 72% (RR: 1.72; 95% CI: 1.33-2.22; P < 0.001), major adverse cardiac events (MACE) by 18% (RR: 1.18; 95% CI: 1.17-1.19; P < 0.001), and stroke by 48% (RR: 1.48; 95% CI: 1.35-1.63; P < 0.001).","evidence_span":"Two source-traced p-values support the dose–response framing of the statin–colorectal cancer association in IBD: P < 0.0001 and P = 0.0007. The directness of this evidence to a dosing/pharmacokinetics outcome is rated indirect, and the effect direction is marked unclear in the source.","excerpt":"BACKGROUND: Patients with a history of malignancy are at elevated risk for acute coronary syndrome (ACS). This study evaluates in-hospital cardiovascular outcomes in ACS patients with and without a cancer history. METHODS: A systematic search of PubMed, Scopus, Embase, and ClinicalTrials.gov (2000-2025) identified studies comparing in-hospital outcomes for ACS in patients with vs. without malignancy. Data were pooled and analyzed using RevMan 5.4, calculating risk ratios (RRs) under a random-effects model. RESULTS: Fifteen studies were included. Among ACS patients, a history of cancer was associated with significantly worse in-hospital outcomes. Cancer history increased all-cause mortality by 44% [RR: 1.44; 95% confidence interval (CI): 1.21-1.71; P < 0.001], bleeding by 72% (RR: 1.72; 95% CI: 1.33-2.22; P < 0.001), major adverse cardiac events (MACE) by 18% (RR: 1.18; 95% CI: 1.17-1.19; P < 0.001), and stroke by 48% (RR: 1.48; 95% CI: 1.35-1.63; P < 0.001). No significant associations were observed for heart failure (RR: 1.24; 95% CI: 0.96-1.59; P = 0.10), re-infarction (RR: 1.17; 95% CI: 0.83-1.65; P = 0.36), or cardiogenic shock (RR: 1.22; 95% CI: 0.97-1.55; P = 0.09)."},{"id":"source_29","type":"source","study":"Feasibility of a mobile application-based geriatric assessment and communication support intervention for older adults with cancer: protocol for a pilot randomised controlled trial (MAPLE2 pilot)","year":2026,"doi":"10.1136/bmjopen-2025-112309","url":"https://doi.org/10.1136/bmjopen-2025-112309","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Matsuoka 2026","quote":"Patients aged≥70 years with solid cancer or lymphoma initiating or changing systemic therapy will undergo baseline GA. Cancer disproportionately affects older adults, with individuals aged≥70 years comprising the majority of patients with cancers in Japan.","evidence_span":"Within the retained source corpus for cancer rates, among adults, do findings for contextual adjacent evidence and cardiometabolic support a decision-grade conclusion (clinically actionable where applicable), and which population, study-design, and directness boundaries keep extrapolation to other outcome classes hypothesis-generating?","excerpt":"INTRODUCTION: Older adults with cancer have ageing-related vulnerabilities that influence their treatment tolerance and decision-making. In our previous randomised controlled trial (MAPLE), integrating geriatric assessment (GA) with communication support using a question prompt list (QPL), delivered by trained intervention providers, facilitated patient-oncologist communication, increased implementation of GA-guided management (GAM) and improved patient outcomes. However, its widespread adoption has been limited by the need for trained personnel and dedicated time. To enhance scalability and sustainability, we developed a mobile application-based intervention to deliver GAM and communication support. This MAPLE2 study aims to evaluate the feasibility of the intervention using this mobile application-based GA and QPL among older adults with cancer. METHODS AND ANALYSIS: This multicentre, open-label, pilot randomised controlled trial will be conducted at two academic hospitals in Japan. Patients aged≥70 years with solid cancer or lymphoma initiating or changing systemic therapy will undergo baseline GA."},{"id":"source_30","type":"source","study":"Management of Bone-Only Progressive Disease in Metastatic Breast Cancer—A Retrospective Single-Center Analysis","year":2026,"doi":"10.3390/jcm15093456","url":"https://doi.org/10.3390/jcm15093456","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Deutschmann 2026","quote":"In 59.3% of bone-only PD cases the systemic treatment was continued with a numerically higher rate if multiple metastatic sites were present (71.4% vs. A RECIST bone-only PD was defined as the appearance of bone lesions with a measurable soft tissue mass larger than 1 cm or an increase of 1 or more bone soft tissue metastases of more than 20% compared to the previous examination.","evidence_span":"Within the corpus, the dosing/pharmacokinetics outcome class contains no non-orthogonal tension pairs, so disagreements cannot be directly surfaced at this granularity. The integrating thesis nonetheless notes that null findings dominate the longevity outcome class and that the Cancer case remains mechanistically plausible but incompletely characterized in human RCT evidence, which limits any inference about a true statin dose–response threshold for colorectal cancer risk reduction.","excerpt":"Background/Objectives: The optimal management of bone-only progressive disease (PD) in metastatic breast cancer remains unclear for several reasons. Radiologic diagnosis of bone PD is complicated by the lack of standardized response assessment criteria, unspecific morphologic changes of the bone, and flare-up phenomena. Furthermore, bone-only disease and oligoprogression have been associated with favorable prognosis challenging a change of systemic treatment with the consequence of limited treatment options in the future. Additionally, bone-only metastatic disease is frequently excluded from clinical trials resulting in scarce data. This study aimed to assess the therapeutic management and outcome of bone-only PD in metastatic breast cancer patients in a real-world academic setting. Methods: A retrospective analysis of all breast cancer patients with bone metastases (BMs) and at least one event of radiologic evidence of bone-only PD and/or the occurrence of a skeletal-related event (SRE) who were treated at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Austria, between 1 January 2015 and 14 December 2021 was performed."},{"id":"source_31","type":"source","study":"Mediterranean diet in cancer patients' survival: A systematic review and meta-analysis for tertiary prevention featured in the Italian National Guidelines \"La Dieta Mediterranea\".","year":2026,"doi":"10.1016/j.nut.2025.113071","url":"https://doi.org/10.1016/j.nut.2025.113071","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Nucci 2026","quote":"Moderate-certainty evidence showed that higher adherence to the MD was associated with reduced overall mortality in cancer patients (risk ratio: 0.96; 95% CI: 0.94-0.98), including subgroups with head and neck (HR: 0.92; 95% CI: 0.84-1.00), ovarian (HR: 0.68; 95% CI: 0.56-0.87), prostate (HR: 0.97; 95% CI: 0.95-0.99), breast (HR: 0.97; 95% CI: 0.96-0.98), and gastric cancer (HR: 0.50; 95% CI: 0.45-0.55). Moderate-certainty evidence supported improved disease-free survival in patients with breast cancer (HR: 0.39; 95% CI: 0.15-0.72).","evidence_span":"In human randomized controlled trials targeting immune-inflammatory endpoints, two recent studies provide contrasting evidence on inflammation modulation in cancer contexts. This ongoing double-blind, placebo-controlled trial in Germany employs a mechanistic biomarker framework to assess inflammation-related outcomes.","excerpt":"BACKGROUND: Cancer remains a leading global health burden, yet survival rates are improving due to better prevention and treatment advances. In this systematic review and meta-analysis we investigate the impact of adherence to the Mediterranean diet (MD) on overall and disease-free survival in cancer patients across various cancer types. METHODS: This review was conducted in accordance with PRISMA 2020 and MOOSE guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Library was performed up to February 28, 2024. Study quality was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence was evaluated with the NUTRIGRADE approach. Pooled effect sizes were computed using a random-effects model and expressed as risk ratios, hazard ratios (HR), or odds ratios. RESULTS: Among 8314 records initially identified, 17 studies were included; sample sizes ranged from 23 to 6457. Moderate-certainty evidence showed that higher adherence to the MD was associated with reduced overall mortality in cancer patients (risk ratio: 0.96; 95% CI: 0.94-0.98), including subgroups with head and neck (HR: 0.92; 95% CI: 0.84-1.00), ovarian (HR: 0.68; 95% CI: 0.56-0."},{"id":"source_32","type":"source","study":"Geriatric Oncology multidomain intervention study to prevent Cognitive impairment among older Indian patients with cancer receiving chemotherapy: a multicentric randomised controlled trial (GOCog)","year":2026,"doi":"10.1186/s12877-026-07513-8","url":"https://doi.org/10.1186/s12877-026-07513-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Noronha 2026","quote":"A review by Janelsins et al. reported that nearly 30% of patients exhibit cognitive decline prior to treatment, 75% have measurable cognitive impairment during chemotherapy, and 35% develop it in the months to years after treatment completion [ 11 ]. A survey of 1,600 survivors found that 75% self-reported cognitive symptoms related to cancer treatments, and most expressed interest in receiving support, particularly cognitive training [ 61 ].","evidence_span":"Population aging confronts health systems with an unusual arithmetic: gains in life expectancy have not produced equivalent gains in years free of chronic disease, and the residual years spent with disability, frailty, and incident cancer dominate late-life burden. This gap between lifespan and healthspan has become a central question in geriatric medicine, prompting renewed interest in whether interventions that act on biology of aging — rather than on single organ diseases — could compress morbidity. Pharmacologic and behavioral strategies that act broadly on aging-related pathways are being explored as adjuncts to disease-specific therapy, particularly in oncology, where the majority of incident cancer and cancer mortality now occur in adults aged 65 and older. The clinical question the field is asking is whether targeting biology of aging can reduce cancer incidence and lengthen healthspan, or whether any putative benefit will be confined to narrower endpoints such as treatment tolerability and functional recovery. The parallel question, whether observed biomarker or mechanistic effects in short windows translate into durable reductions in cancer rates at the population level, remains open and is the focus of this synthesis. Across the curated 39-study evidence base examined here, signals are context-dependent and the case is incomplete: mechanistic plausibility coexists with mixed human randomized evidence and with sparse null findings on hard endpoints.","excerpt":"BACKGROUND: Chemotherapy-related cognitive dysfunction is a common adverse effect in older adults receiving cancer-directed therapy, impairing independence, treatment adherence, and quality of life. Evidence from India is limited, and culturally adapted interventions are lacking. We aim to assess (i) the effectiveness of a multidomain intervention (exercise and cognitive training) on cognition, function, and quality of life; (ii) the feasibility and compliance to the intervention; and (iii) exploratory imaging and biomarker correlates. METHODS: We will conduct a multicentric randomised controlled trial with two parallel arms among patients ≥ 60 years planned for systemic chemotherapy at Tata Memorial Centre (Mumbai) and Medical Trust Hospital (Kochi). A total of 364 participants will be randomised 1:1 to the intervention group (exercise + cognitive training) or control group (usual care). The intervention will consist of a 3-month program combining supervised and home-based aerobic, resistance exercises and structured cognitive training activities."},{"id":"source_33","type":"source","study":"Cardiovascular Vulnerability, Including Heart Failure Risk, in Breast Cancer Surgery: The Role of Operative Technique, Frailty, and Postoperative Complications","year":2026,"doi":"10.3390/medicina62050877","url":"https://doi.org/10.3390/medicina62050877","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Marginean 2026","quote":"Studies were included if they were original research articles (retrospective or prospective cohort studies, registry-based analyses, or large administrative database studies) that met the following criteria: (1) evaluated adult patients (≥18 years) undergoing breast cancer surgery, including breast-conserving surgery, mastectomy, oncoplastic procedures, or any form of immediate or delayed reconstruction; (2) reported extractable postoperative outcomes within 30 days or during the index hospitalization; and (3) included data on at least one of the following domains: cardiovascular comorbidities (including heart failure), cardiovascular risk factors, or frailty assessment. Thirteen reports were excluded following full-text review due to lack of relevant postoperative outcomes ( n = 5), insufficient or non-extractable data ( n = 3), lack of focus on breast cancer surgery ( n = 3), or inelig","evidence_span":"Evidence for this outcome class is represented in the structured results table, but the retained narrative paragraphs were more strongly assigned to adjacent outcome classes. The synthesis therefore treats this class as context for cross-domain interpretation rather than as a standalone prose claim.","excerpt":"Background and Objectives : Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global perioperative complication rates and composite medical endpoints, with heart failure events only rarely captured as dedicated outcomes, and operative technique, cardiovascular comorbidity, and frailty are often treated as separate domains rather than components of an integrated risk framework. Materials and Methods : We conducted a systematized narrative review with a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science from inception to 31 January 2026, including original studies of adult patients undergoing breast-conserving surgery, mastectomy, and/or reconstruction that reported early postoperative outcomes in relation to comorbidities, cardiovascular risk, or frailty."},{"id":"source_34","type":"source","study":"Asynchronous telerehabilitation in prehabilitation and postoperative recovery for colorectal cancer: A protocol for a randomized controlled trial","year":2026,"doi":"10.1371/journal.pone.0333649","url":"https://doi.org/10.1371/journal.pone.0333649","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Burgos-Bragado 2026","quote":"The World Health Organization (WHO) reports that CRC is the third most frequently diagnosed cancer and the second leading cause of cancer-related death worldwide, accounting for nearly 10% of all cases and 9.6% of annual cancer deaths [ 11 ]. The exclusion criteria will be: 1) Patients over 80 years old; 2) Preoperative ASA classification IV; 3) Musculoskeletal, inflammatory or other pathological conditions preventing physical exercise; 4) Central and/or peripheral neurological disorders limiting participation in the rehabilitation program; 5) Unstable concomitant cardiac conditions, including cardiac arrhythmias, hypertension, angina or other conditions contraindicating moderate-intensity exercise; 6) Psychiatric disorders diagnosed by a psychiatrist; 7) Lack of access to an internet-enabled mobile device or computer at home; and 8) Refusal to participate or lack of a signed consent for","evidence_span":"The geroscience hypothesis offers a unifying logic for studying such interventions: if multiple chronic diseases of aging share upstream mechanisms (chronic inflammation, cellular senescence, mitochondrial dysfunction, altered proteostasis), then a single intervention that modulates those mechanisms might yield parallel benefits across endpoints. In oncology specifically, the rationale is that the same biology that drives sarcopenia, frailty, cardiometabolic decline, and immune dysregulation also drives carcinogenesis, treatment toxicity, and recurrence risk. This logic has motivated evaluation both of repurposed drugs with decades of safety data and of novel agents designed against aging-relevant pathways. Repurposing shortens development timelines and lowers cost, but introduces tension when a drug's effects on cancer rates must be inferred from studies whose primary endpoint was metabolic, cardiovascular, or functional rather than oncologic. Novel agents face the inverse problem: cleaner mechanistic targeting but limited long-term safety data in older adults who carry the highest cancer rates.","excerpt":"INTRODUCTION: Colorectal cancer (CRC) is a leading global malignancy, and surgery is frequently followed by complications, functional decline, and reduced quality of life. Multimodal prehabilitation and rehabilitation can improve physical recovery and psychosocial outcomes, but uptake is often limited by logistical and mobility barriers. Asynchronous telerehabilitation offers a flexible, patient-centered, and scalable approach; however, its effectiveness across the perioperative CRC pathway has not been rigorously evaluated. This trial will evaluate a multimodal asynchronous program delivered in prehabilitation and postoperative phases, against a booklet-based usual-care approach reflecting the pre-existing perioperative pathway in the study setting before trial initiation. METHODS: This single-blind, parallel-group randomized controlled trial will compare an asynchronous multimodal telerehabilitation program with a booklet-based usual-care program in adults scheduled for elective CRC resection. Fifty-six participants will be randomized 1:1 to the telerehabilitation group (HEFORA platform) or the usual-care control group."},{"id":"source_35","type":"source","study":"“Having surgery is necessary” – a qualitative analysis of the experiences of frail older adults treated with, and recovering from colorectal cancer surgery","year":2026,"doi":"10.1186/s12877-026-07356-3","url":"https://doi.org/10.1186/s12877-026-07356-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Normann 2026","quote":"Colorectal cancer is the third most common cancer globally, most new cases are amongst people ≥ 70 years, and the incidence is increasing [ 1 - 3 ]. Patients eligible for inclusion in the CRC Frailty study were recently diagnosed with a colorectal cancer where curatively intended surgery was deemed possible, were aged ≥ 65 years and without significant cognitive impairment or language limitations.","evidence_span":"Exact hazard-ratio point estimates are not provided in the source excerpt and are therefore not reproduced here. Per-study endpoint detail is consolidated in the evidence synthesis.","excerpt":"BACKGROUND: Frail older adults undergoing surgical treatment for colorectal cancer are at increased risk of postoperative mortality and complications compared with non-frail older adults. Even though these risks are established, limited research has explored patient perspectives on surgical treatment and recovery in frail older adults. This study aimed to explore the experiences of frail older adults during diagnosis, treatment, and recovery from surgically treated colorectal cancer. METHODS: Participants were recruited through purposive sampling from the control group of the randomized controlled trial “Effect of comprehensive geriatric assessment for frail elderly patients operated for colorectal cancer – the Colorectal Cancer Frailty Study.” Patients in the control group receive standardised treatment according to best practice within an ERAS-concept. Sixteen semi-structured interviews were conducted 6–22 months post-surgery. All interviews were audio-recorded, transcribed verbatim, and analysed using qualitative content analysis with a focus on both manifest and latent content. RESULTS: Participants perceived surgery as essential for survival."},{"id":"source_36","type":"source","study":"Comparative efficacy of aerobic exercise and mind-body practices in improving sleep quality and psychological distress among elderly breast cancer patients: a systematic review","year":2026,"doi":"10.3389/fonc.2026.1798402","url":"https://doi.org/10.3389/fonc.2026.1798402","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Cui 2026","quote":"For example, a study investigating exercise adherence among breast cancer patients undergoing aerobic and resistance training during or after neoadjuvant chemotherapy included only 68 participants with an average age of 52 years, failing to specifically focus on the elderly population ( 79 ). For example, a mixed-methods randomized controlled trial exploring the effects of Guolin Qigong on cancer-related fatigue set its intervention cycle at 12 weeks with a 4-week follow-up period ( 75 ).","evidence_span":"Per the brief, indirect and direct evidence are kept analytically separate; the apparent disagreement between a positive RCT signal and a null pooled estimate therefore reflects different evidentiary roles rather than contradicting findings on the same question.","excerpt":"Elderly breast cancer patients often face severe sleep disturbances and psychological distress due to the disease itself and its treatment process, significantly reducing their quality of life. In recent years, non-pharmacological interventions, represented by aerobic exercise and mind-body practices, have demonstrated great potential in improving the physical and mental health of patients. This paper aims to systematically review existing literature and compare the effects of aerobic exercise and mind-body practices on sleep quality and psychological distress in elderly breast cancer patients. The review focuses on analyzing the similarities and differences between the two intervention approaches in improving sleep architecture, alleviating psychological stress including anxiety and depression, and their associated physiological mechanisms. By synthesizing the latest evidence from clinical trials and intervention studies, this paper explores the clinical application value of these two intervention strategies, identifies current research limitations, and suggests future research directions."},{"id":"source_37","type":"source","study":"Multimodal Prehabilitation In Pancreatic cancer Patients undergoing surgery (PIPS): study protocol for a randomized controlled trial","year":2026,"doi":"10.1186/s13063-026-09467-z","url":"https://doi.org/10.1186/s13063-026-09467-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"some_concerns","directness":"direct","cited_as":"Pecorelli 2026","quote":"Pancreatic cancer surgery is challenging and associated with up to a 70% complication rate, which translates to poor postoperative recovery and patient health-related quality of life (HRQoL). Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with a 5-year survival rate of around 10% [ 1 ].","evidence_span":"Findings Map completeness note: all 39 admitted manifest rows are surfaced below; outcome class follows endpoint/source context before topic keywords.","excerpt":"BACKGROUND: Pancreatic cancer surgery is challenging and associated with up to a 70% complication rate, which translates to poor postoperative recovery and patient health-related quality of life (HRQoL). Previous studies showed that preoperative low functional capacity and malnutrition have been associated with inferior postoperative outcomes. Considering the high frequency of older and frail patients, often deconditioned by long-course neoadjuvant chemotherapy, the preoperative period, including the time window after chemotherapy, is a unique opportunity to condition modifiable risk factors (e.g., functional capacity, nutritional status). This manuscript outlines the protocol for a randomized controlled trial investigating the impact of a multimodal prehabilitation program on postoperative complications and recovery following pancreatectomy. METHODS: This is a single-center, randomized controlled trial evaluating a 4-6-week multimodal prehabilitation program (physical, nutritional, and psychological interventions) compared with usual perioperative care in adults scheduled for pancreatic surgery, whether upfront or following chemotherapy for pancreatic or periampullary cancer."},{"id":"source_38","type":"source","study":"Immune Checkpoint Inhibitors in Elderly Patients With Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Subgroup Evidence.","year":2026,"doi":"10.1016/j.clbc.2026.04.005","url":"https://doi.org/10.1016/j.clbc.2026.04.005","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Carlos 2026","quote":"Results ICIs improved PFS in the intention-to-treat population (HR 0.69; 95% CI 0.56-0.86; I² = 0%), while OS improvement did not reach statistical significance (HR 0.83; 95% CI 0.69-1.01; I² = 0%). In PD-L1-positive subgroups, pooled results showed reduced mortality risk (OS HR 0.70; 95% CI 0.49-1.01; I² = 28.9%) and a nonsignificant trend toward improvement in PFS (HR 0.71; 95% CI 0.43-1.16; I² = 50.5%).","evidence_span":"Because the source carries an empty p values array and does not report a hazard ratio, odds ratio, or relative risk for fracture incidence, the quantitative findings are limited to the descriptive systemic-treatment-continuation percentages cited above. No confidence intervals, follow-up duration, or dose information are present in the supplied excerpt, and the source's directness flag is indirect with respect to the broad Cancer topic. The interpretive consequence is that this outcome class is supported by descriptive proportions only, not by inferential statistics suitable for cross-study pooling.","excerpt":"BACKGROUND: Immune checkpoint inhibitors (ICIs) have advanced the treatment for triple-negative breast cancer (TNBC), but evidence in older adults remains limited. This study assessed the efficacy and safety of ICIs in elderly patients through a systematic review and meta-analysis of randomized clinical trials METHODS: A systematic search identified trials evaluating ICIs in TNBC. Data from nine studies were pooled using random-effects models. Subgroup analyses examined progression-free survival (PFS) and overall survival (OS) in PD-L1-positive tumors and adults aged ≥65 years. RESULTS: ICIs improved PFS in the intention-to-treat population (HR 0.69; 95% CI 0.56-0.86; I² = 0%), while OS improvement did not reach statistical significance (HR 0.83; 95% CI 0.69-1.01; I² = 0%). In PD-L1-positive subgroups, pooled results showed reduced mortality risk (OS HR 0.70; 95% CI 0.49-1.01; I² = 28.9%) and a nonsignificant trend toward improvement in PFS (HR 0.71; 95% CI 0.43-1.16; I² = 50.5%). Benefits were consistent in sensitivity analyses and in adults aged 65 years or older."},{"id":"source_39","type":"source","study":"Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial.","year":2026,"doi":"10.1001/jamaoncol.2025.6196","url":"https://doi.org/10.1001/jamaoncol.2025.6196","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Orchard 2026","quote":"Importance Prior studies, largely among middle-aged adults, reported aspirin reduces cancer risk after 10 years, particularly for colorectal cancer (CRC). In contrast, the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial (RCT) reported that low-dose aspirin (LDA) treatment for a median of 4.7 years had no effect on overall cancer incidence but increased risk of incident late-stage cancer and cancer-related mortality.","evidence_span":"Within the corpus, this outcome class has no tension pairs in the cross-study disagreement map, so there are no within-corpus disagreements to surface for the bone endpoint. Readers should treat the bone subsection as a descriptive anchor rather than as a causal estimate of fracture risk in the Cancer domain.","excerpt":"IMPORTANCE: Prior studies, largely among middle-aged adults, reported aspirin reduces cancer risk after 10 years, particularly for colorectal cancer (CRC). In contrast, the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial (RCT) reported that low-dose aspirin (LDA) treatment for a median of 4.7 years had no effect on overall cancer incidence but increased risk of incident late-stage cancer and cancer-related mortality. OBJECTIVE: To assess whether LDA is associated with cancer incidence and mortality in 10 years of follow-up in older adults (aged ≥70 years) and to assess the association with cancer after prior LDA exposure (legacy effects). DESIGN, SETTING, AND PARTICIPANTS: This community-based binational (Australian and US) cohort study included community-dwelling older adults (aged ≥70 years for Australian participants and ≥65 years for US minority group participants) free from overt cardiovascular disease, dementia, or independence-limiting physical disability. The cohort was derived from the ASPREE randomized clinical trial conducted from 2010 to 2017, with the observational extension study (ASPREE-XT) following up participants from 2018 to 2024."}],"edges":[{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_1","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_2","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_3","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_4","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_5","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_6","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_7","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_8","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_9","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_10","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_11","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_12","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_13","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_14","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_15","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_16","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_17","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_18","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_19","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_20","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_21","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_22","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_23","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_24","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_25","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_26","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_27","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_28","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_29","type":"contains_claim"},{"from":"db433f84-030f-4867-807f-8b21fe4b1673","to":"claim_30","type":"contains_claim"}],"screening":{"identified":39,"screened":39,"excluded":0,"included":39,"included_or_retained":39,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"39 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}