Derivation Web

source_8577f04ac529457c

by researka:v2 · 2026-07-17 16:38:37.947187+04:00

{"content_hash": "sha256:5b461a0ca2ffde54d7d9282566c0b574387153b4da1fa6b66135569b35f0981c", "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"}], "nodes": [{"id": "db433f84-030f-4867-807f-8b21fe4b1673", "title": "Adjacent Evidence Brief: Cancer Rates — full paper", "type": "publication"}, {"id": "claim_1", "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.", "type": "claim"}, {"id": "claim_2", "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.", "type": "claim"}, {"id": "claim_3", "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.", "type": "claim"}, {"id": "claim_4", "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.", "type": "claim"}, {"id": "claim_5", "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.", "type": "claim"}, {"id": "claim_6", "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.", "type": "claim"}, {"id": "claim_7", "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.", "type": "claim"}, {"id": "claim_8", "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?", "type": "claim"}, {"id": "claim_9", "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.", "type": "claim"}, {"id": "claim_10", "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.", "type": "claim"}, {"id": "claim_11", "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]", "type": "claim"}, {"id": "claim_12", "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]", "type": "claim"}, {"id": "claim_13", "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]", "type": "claim"}, {"id": "claim_14", "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]", "type": "claim"}, {"id": "claim_15", "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.", "type": "claim"}, {"id": "claim_16", "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.", "type": "claim"}, {"id": "claim_17", "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.", "type": "claim"}, {"id": "claim_18", "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.", "type": "claim"}, {"id": "claim_19", "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.", "type": "claim"}, {"id": "claim_20", "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.", "type": "claim"}, {"id": "claim_21", "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.", "type": "claim"}, {"id": "claim_22", "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.", "type": "claim"}, {"id": "claim_23", "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.", "type": "claim"}, {"id": "claim_24", "text": "| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |", "type": "claim"}, {"id": "claim_25", "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]", "type": "claim"}, {"id": "claim_26", "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]", "type": "claim"}, {"id": "claim_27", "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]", "type": "claim"}, {"id": "claim_28", "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]", "type": "claim"}, {"id": "claim_29", "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]", "type": "claim"}, {"id": "claim_30", "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]", "type": "claim"}, {"cited_as": "Lee 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1186/s12877-026-06995-w", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Long-term outcomes in elderly colorectal cancer patients with presarcopenia: a single center retrospective cohort study", "type": "source", "url": "https://doi.org/10.1186/s12877-026-06995-w", "year": 2026}, {"cited_as": "Li 2026a", "comparator": "not extracted", "directness": "indirect", "doi": "10.3389/fonc.2026.1728009", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "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 .", "risk_of_bias": "not appraised in public sidecar", "study": "Cancer and the risk of death, heart-failure hospitalization, and major adverse cardiovascular events in HFpEF: a propensity-matched cohort study", "type": "source", "url": "https://doi.org/10.3389/fonc.2026.1728009", "year": 2026}, {"cited_as": "Sahin 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1186/s12877-026-07255-7", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "study": "Can the frailty score independently predict postoperative morbidity in patients with colorectal cancer? A prospective observational study", "type": "source", "url": "https://doi.org/10.1186/s12877-026-07255-7", "year": 2026}, {"cited_as": "Jin 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1186/s13048-026-01982-6", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of pre-operative frailty on short-term outcomes of ovarian cancer: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1186/s13048-026-01982-6", "year": 2026}, {"cited_as": "Torres 2025", "comparator": "not extracted", "directness": "review", "doi": "10.1093/nutrit/nuaf137", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Long-Term Effectiveness of Dietary Interventions on Inflammatory Biomarkers in Women with Breast Cancer: A Systematic Review and Meta-Analysis", "type": "source", "url": "https://doi.org/10.1093/nutrit/nuaf137", "year": 2025}, {"cited_as": "Houdt 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1016/j.esmoop.2025.105896", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "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", "type": "source", "url": "https://doi.org/10.1016/j.esmoop.2025.105896", "year": 2026}, {"cited_as": "Anker 2025", "comparator": "not extracted", "directness": "indirect", "doi": "10.1093/eurheartj/ehaf705", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "study": "Heart failure therapy in patients with advanced cancer receiving specialized palliative care (EMPATICC trial)", "type": "source", "url": "https://doi.org/10.1093/eurheartj/ehaf705", "year": 2025}, {"cited_as": "Svendsen 2026", "comparator": "not extracted", "directness": "review", "doi": "10.2340/1651-226X.2026.45726", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "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 ].", "risk_of_bias": "not appraised in public sidecar", "study": "Change in skeletal muscle mass during systemic cancer treatment: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.2340/1651-226X.2026.45726", "year": 2026}, {"cited_as": "Hernandez-Garcia 2026", "comparator": "not extracted", "directness": "protocol", "doi": "10.1136/bmjopen-2025-111748", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "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", "type": "source", "url": "https://doi.org/10.1136/bmjopen-2025-111748", "year": 2026}, {"cited_as": "Zopf 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1186/s13058-026-02235-6", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "some_concerns", "study": "Exercise effects on lean body mass, muscle strength and functional performance in patients with metastatic breast cancer: the randomized controlled PREFERABLE-EFFECT study", "type": "source", "url": "https://doi.org/10.1186/s13058-026-02235-6", "year": 2026}, {"cited_as": "Asencio-Mas 2026", "comparator": "not extracted", "directness": "review", "doi": "10.3390/nu18111815", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Diet and Exercise Lifestyle Interventions on Physical and Psychological Health in Breast Cancer Survivors: A Systematic Review", "type": "source", "url": "https://doi.org/10.3390/nu18111815", "year": 2026}, {"cited_as": "Fujimoto 2025", "comparator": "not extracted", "directness": "indirect", "doi": "10.1111/jdi.70224", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "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%).", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of diabetes mellitus and grip strength on postoperative outcomes in older patients undergoing cancer surgery: A single‐center retrospective cohort study", "type": "source", "url": "https://doi.org/10.1111/jdi.70224", "year": 2025}, {"cited_as": "Li 2026b", "comparator": "not extracted", "directness": "indirect", "doi": "10.2147/CIA.S589717", "effect": "not extracted", "endpoint": "not extracted", "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 |", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of Preoperative Frailty on Postoperative Complications and Cognitive Impairment in Liver Cancer Patients: An Observational Cohort Study", "type": "source", "url": "https://doi.org/10.2147/CIA.S589717", "year": 2026}, {"cited_as": "Ruiz-Campos 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1136/bjsports-2025-110756", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "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", "type": "source", "url": "https://doi.org/10.1136/bjsports-2025-110756", "year": 2026}, {"cited_as": "Gao 2026", "comparator": "not extracted", "directness": "review", "doi": "10.3389/fonc.2026.1789366", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "Cardiometabolic: n=5; claims=534; mixed signal in 2/5 sources | directness: 3 indirect; 2 review; main limitation: no direct clinical anchor.", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "study": "Association between malnutrition and prognosis in colorectal cancer: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.3389/fonc.2026.1789366", "year": 2026}, {"cited_as": "Ji 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1001/jamanetworkopen.2026.3541", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Long-Term Outcomes of Concurrent Chemoradiotherapy With S-1 in Older Patients With Esophageal Cancer", "type": "source", "url": "https://doi.org/10.1001/jamanetworkopen.2026.3541", "year": 2026}, {"cited_as": "Gwenzi 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1038/s41416-025-03333-6", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "some_concerns", "study": "Effects of personalized vitamin D 3 on inflammation in colorectal cancer patients: a randomized trial", "type": "source", "url": "https://doi.org/10.1038/s41416-025-03333-6", "year": 2026}, {"cited_as": "Hu 2025", "comparator": "not extracted", "directness": "direct", "doi": "10.3802/jgo.2026.37.e33", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "some_concerns", "study": "Lobaplatin versus cisplatin in concurrent chemoradiotherapy for elderly cervical cancer: randomized controlled phase II study", "type": "source", "url": "https://doi.org/10.3802/jgo.2026.37.e33", "year": 2025}, {"cited_as": "Rajamaki 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1002/pds.70416", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_19", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "study": "Age, Age‐Related Comorbidities and Survival in Palbociclib, Ribociclib and Abemaciclib Users With Advanced Breast Cancer: A Nation‐Wide Retrospective Cohort Study", "type": "source", "url": "https://doi.org/10.1002/pds.70416", "year": 2026}, {"cited_as": "Zhang 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1186/s12871-026-03733-y", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_20", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "some_concerns", "study": "Intravenous lidocaine reduces systemic inflammation but not myocardial injury following thoracic surgery for lung cancer: a randomized controlled trial", "type": "source", "url": "https://doi.org/10.1186/s12871-026-03733-y", "year": 2026}, {"cited_as": "RamirezGiraldo 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1002/cam4.71927", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "Immune and Inflammation: n=3; claims=156; mixed signal in 2/3 sources | directness: 2 direct; 1 protocol; main limitation: directionally heterogeneous.", "id": "source_21", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "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", "type": "source", "url": "https://doi.org/10.1002/cam4.71927", "year": 2026}, {"cited_as": "Ding 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1038/s41598-026-49287-4", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_22", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "some_concerns", "study": "Esketamine-sufentanil PCA reduces postoperative depression state in elderly colorectal cancer patients: a randomized controlled trial", "type": "source", "url": "https://doi.org/10.1038/s41598-026-49287-4", "year": 2026}, {"cited_as": "Galavotti 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.3390/curroncol33060313", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "Muscle Function: n=2; claims=147; mixed signal in 1/2 sources | directness: 1 direct; 1 review; main limitation: directionally heterogeneous.", "id": "source_23", "intervention_or_exposure": "not extracted", "population": "not extracted", "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 ].", "risk_of_bias": "not appraised in public sidecar", "study": "Integrating Exercise and Education into Lung Cancer Care: Results from the OVER-CRF Pilot Study on Cancer-Related Fatigue and Quality of Life", "type": "source", "url": "https://doi.org/10.3390/curroncol33060313", "year": 2026}, {"cited_as": "Huang 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1186/s12885-026-15970-y", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_24", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Dose–response effect of statins on colorectal cancer risk in IBD: a nationwide cohort study", "type": "source", "url": "https://doi.org/10.1186/s12885-026-15970-y", "year": 2026}, {"cited_as": "Yuan 2026", "comparator": "not extracted", "directness": "review", "doi": "10.3389/fonc.2026.1796138", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_25", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "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", "type": "source", "url": "https://doi.org/10.3389/fonc.2026.1796138", "year": 2026}, {"cited_as": "Veenhuizen 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1136/bmjopen-2026-117251", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_26", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "some_concerns", "study": "Effect of yoga on musculoskeletal complaints in women during endocrine treatment for breast cancer: protocol of the randomised controlled COBRA trial", "type": "source", "url": "https://doi.org/10.1136/bmjopen-2026-117251", "year": 2026}, {"cited_as": "Peker 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.3389/fnut.2026.1745718", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "Quantitative findings from the surgical and supportive-care literature further populate the contextual outcome space.", "id": "source_27", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of prognostic nutritional index and geriatric nutritional risk index on prognosis in elderly patients with early-stage prostate cancer", "type": "source", "url": "https://doi.org/10.3389/fnut.2026.1745718", "year": 2026}, {"cited_as": "Ahmad 2026", "comparator": "not extracted", "directness": "review", "doi": "10.2459/jcm.0000000000001894", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_28", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "study": "In-hospital outcomes of acute coronary syndrome in patients with cancer: a systematic review and meta-analysis.", "type": "source", "url": "https://doi.org/10.2459/jcm.0000000000001894", "year": 2026}, {"cited_as": "Matsuoka 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1136/bmjopen-2025-112309", "effect": "not extracted", "endpoint": "not extracted", "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?", "id": "source_29", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "some_concerns", "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)", "type": "source", "url": "https://doi.org/10.1136/bmjopen-2025-112309", "year": 2026}, {"cited_as": "Deutschmann 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.3390/jcm15093456", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_30", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Management of Bone-Only Progressive Disease in Metastatic Breast Cancer—A Retrospective Single-Center Analysis", "type": "source", "url": "https://doi.org/10.3390/jcm15093456", "year": 2026}, {"cited_as": "Nucci 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1016/j.nut.2025.113071", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_31", "intervention_or_exposure": "not extracted", "population": "not extracted", "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).", "risk_of_bias": "not appraised in public sidecar", "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\".", "type": "source", "url": "https://doi.org/10.1016/j.nut.2025.113071", "year": 2026}, {"cited_as": "Noronha 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1186/s12877-026-07513-8", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_32", "intervention_or_exposure": "not extracted", "population": "not extracted", "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 ].", "risk_of_bias": "some_concerns", "study": "Geriatric Oncology multidomain intervention study to prevent Cognitive impairment among older Indian patients with cancer receiving chemotherapy: a multicentric randomised controlled trial (GOCog)", "type": "source", "url": "https://doi.org/10.1186/s12877-026-07513-8", "year": 2026}, {"cited_as": "Marginean 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.3390/medicina62050877", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_33", "intervention_or_exposure": "not extracted", "population": "not extracted", "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", "risk_of_bias": "not appraised in public sidecar", "study": "Cardiovascular Vulnerability, Including Heart Failure Risk, in Breast Cancer Surgery: The Role of Operative Technique, Frailty, and Postoperative Complications", "type": "source", "url": "https://doi.org/10.3390/medicina62050877", "year": 2026}, {"cited_as": "Burgos-Bragado 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1371/journal.pone.0333649", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_34", "intervention_or_exposure": "not extracted", "population": "not extracted", "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", "risk_of_bias": "some_concerns", "study": "Asynchronous telerehabilitation in prehabilitation and postoperative recovery for colorectal cancer: A protocol for a randomized controlled trial", "type": "source", "url": "https://doi.org/10.1371/journal.pone.0333649", "year": 2026}, {"cited_as": "Normann 2026", "comparator": "not extracted", "directness": "indirect", "doi": "10.1186/s12877-026-07356-3", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_35", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "“Having surgery is necessary” – a qualitative analysis of the experiences of frail older adults treated with, and recovering from colorectal cancer surgery", "type": "source", "url": "https://doi.org/10.1186/s12877-026-07356-3", "year": 2026}, {"cited_as": "Cui 2026", "comparator": "not extracted", "directness": "review", "doi": "10.3389/fonc.2026.1798402", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_36", "intervention_or_exposure": "not extracted", "population": "not extracted", "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 ).", "risk_of_bias": "not appraised in public sidecar", "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", "type": "source", "url": "https://doi.org/10.3389/fonc.2026.1798402", "year": 2026}, {"cited_as": "Pecorelli 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1186/s13063-026-09467-z", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "Findings Map completeness note: all 39 admitted manifest rows are surfaced below; outcome class follows endpoint/source context before topic keywords.", "id": "source_37", "intervention_or_exposure": "not extracted", "population": "not extracted", "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 ].", "risk_of_bias": "some_concerns", "study": "Multimodal Prehabilitation In Pancreatic cancer Patients undergoing surgery (PIPS): study protocol for a randomized controlled trial", "type": "source", "url": "https://doi.org/10.1186/s13063-026-09467-z", "year": 2026}, {"cited_as": "Carlos 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1016/j.clbc.2026.04.005", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_38", "intervention_or_exposure": "not extracted", "population": "not extracted", "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%).", "risk_of_bias": "not appraised in public sidecar", "study": "Immune Checkpoint Inhibitors in Elderly Patients With Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Subgroup Evidence.", "type": "source", "url": "https://doi.org/10.1016/j.clbc.2026.04.005", "year": 2026}, {"cited_as": "Orchard 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1001/jamaoncol.2025.6196", "effect": "not extracted", "endpoint": "not extracted", "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.", "id": "source_39", "intervention_or_exposure": "not extracted", "population": "not extracted", "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.", "risk_of_bias": "not appraised in public sidecar", "study": "Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial.", "type": "source", "url": "https://doi.org/10.1001/jamaoncol.2025.6196", "year": 2026}], "publication_id": "db433f84-030f-4867-807f-8b21fe4b1673", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 39, "included": 39, "included_or_retained": 39, "screened": 39, "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."}}

{
  "researka_object_type": "publication_sidecar",
  "researka_publication_id": "db433f84-030f-4867-807f-8b21fe4b1673",
  "researka_submission_id": "a88c56c9-38f5-4a28-a85c-f4ee510aaa33",
  "sidecar_name": "claim_graph.json",
  "sidecar_url": "https://api.researka.org/publications/db433f84-030f-4867-807f-8b21fe4b1673/sidecars/claim_graph.json"
}