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Bioscientia Medicina : Journal of Biomedicine and Translational Research

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Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Neuroscience

BioScientia Medicina is an open access international scholarly journal in the field of biomedicine and translational research aimed to publish a high-quality scientific paper including original research papers, reviews, short communication, and technical notes. This journal welcomes the submission of articles that offering a sensible transfer of basic research to applied clinical medicine. BioScientia Medicina covers the latest developments in various fields of biomedicine with special attention to medical sciences, Traditional Herb, genetics, immunology, environmental health, toxicology, bioinformatics and biotechnology as well as multidisciplinary studies. The views of experts on current advances in nanotechnology and molecular/cell biology will be also considered for publication as long as they have a direct clinical impact on human health.

Arjuna Subject : Kedokteran - Anatomi

Articles 1,290 Documents

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Menopausal Status as the Strongest Independent Predictor of Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer Stephen William Soeseno; I Wayan Sudarsa; Ni Gusti Ayu Agung Manik Yuniawaty Wetan
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 6 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i6.1621

Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer (LABC), yet predicting individual patient response remains challenging. This study investigates menopausal status and other clinicopathological factors as predictors of NAC response in a Southeast Asian population. Methods: This retrospective cohort study analyzed 247 LABC patients treated with NAC between 2022–2023 at the Oncology Surgery Division, Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Bali. Variables included menopausal status (premenopausal vs. postmenopausal), histological type, histological grading, molecular subtype, lymphovascular invasion (LVI), tumor-infiltrating lymphocytes (TIL), and age. Bivariate analysis used chi-square tests; multivariate logistic regression identified independent predictors. Results: Among 247 patients (mean age 51.7 ± 9.1 years), 130 (52.6%) achieved positive response. Postmenopausal patients demonstrated significantly higher response rates (79.7% vs. 12.1%, p<0.001). Multivariate analysis revealed menopausal status as the strongest predictor (OR=14.999, 95%CI: 6.045–37.213, p<0.001), followed by molecular subtype (OR=4.182, p=0.006), histological grading (OR=3.596, p=0.010), and histological type (OR=0.367, p=0.017). Age, LVI, and TIL lost statistical significance in the multivariate model. Conclusion: Menopausal status emerged as the strongest independent predictor of NAC response in LABC, suggesting that hormonal factors play a pivotal role in chemotherapy sensitivity. These findings support more aggressive NAC regimens or combined endocrine-cytotoxic strategies for postmenopausal patients and warrant validation in prospective Southeast Asian cohorts.

Efficacy and Safety of Travoprost Intraocular Implants in Open-Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis Jovita Jutamulia; Agnestya Christine Zely Raule
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1628

Background: Open-angle glaucoma (OAG) and ocular hypertension (OHT) are leading causes of irreversible visual impairment and require lifelong reduction of intraocular pressure (IOP). Topical prostaglandin analogues are the standard first-line therapy, yet their effectiveness is constrained by poor adherence. The travoprost 75 µg intracameral implant has emerged as a sustained-release alternative designed to bypass these adherence barriers. The present systematic review and meta-analysis quantitatively synthesised the efficacy and safety of this device in adults with OAG or OHT. Methods: PubMed was searched in accordance with the PRISMA 2020 statement. Original research articles evaluating the travoprost 75 µg intracameral implant in adults with OAG or OHT were eligible. Two reviewers screened, extracted data, and independently appraised risk of bias using Cochrane RoB 2.0 (RCTs) or the Newcastle–Ottawa Scale (non-randomised). Standardised mean changes in IOP were synthesised as Hedges' g under a DerSimonian–Laird random-effects model with Knapp–Hartung adjustment. Pre-specified sensitivity, leave-one-out, alternative-pool, and design sub-group analyses were performed. The funnel plot was inspected; Egger's test was deferred because k < 10. Results: Of 30 PubMed records, 10 original research studies were eligible and 6 contributed to the primary quantitative synthesis (2,152 total enrolled participants; 1,525 implant-arm participants pooled in the within-group synthesis). The pooled within-group Hedges' g for IOP reduction was 4.35 (95% CI 3.14 to 5.56; p = 0.0002). Heterogeneity was very high (I² = 96.1%, τ² = 1.121, Q = 53.64, p < 0.0001). The 95% prediction interval, derived from the same model, spanned approximately 1.13 to 7.56. The randomised-controlled-trial-only pool (k = 4) yielded a more conservative pooled estimate of g = 3.76 (95% CI 2.94 to 4.58; I² = 88.6%). Leave-one-out analyses confirmed robustness (g range 3.98–4.56). Serious ocular adverse events were rare (one endophthalmitis in the slow-eluting arm of the GC-010 phase 3 trial, with no further cases in the remaining cohorts); transient ocular hyperemia, iritis, and elevated IOP were the most common, broadly consistent with the topical-travoprost class profile. Conclusion: The travoprost 75 µg intracameral implant produced a large and consistent reduction in IOP across designs and follow-up windows, with a safety profile non-inferior to topical timolol 0.5%. The substantial heterogeneity, near-uniform sponsor footprint, and limited head-to-head comparisons against topical prostaglandin monotherapy temper the certainty of the evidence and warrant pragmatic, independent, multi-ethnic trials. Within these limits, the implant is a clinically meaningful addition to interventional glaucoma therapy, particularly for patients in whom topical adherence is the dominant driver of disease progression.

Single-Stage Bilateral Sinusectomy with Methylene Blue Tract Delineation for Familial Classic Preauricular Sinus Following Right-Sided Abscess Control: A Case Report Jihan Mudrika Rahmi; Al Hafiz
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1630

Background. Preauricular sinus is a congenital anomaly arising from incomplete fusion of the auricular hillocks of the first and second branchial arches. The condition shows marked ethnic variation, with bilateral presentations strongly associated with hereditary transmission. Surgical excision remains the only definitive treatment for symptomatic or recurrently infected lesions, yet operative recurrence rates of up to 42% have been historically reported. Case presentation. A 24-year-old Indonesian Minangkabau male presented with bilateral preauricular openings present since birth and a recent right preauricular abscess that had been treated with incision and drainage twenty days prior. His father had a unilateral left-sided preauricular pit, consistent with familial transmission. Examination confirmed bilateral classic-type preauricular fistulae anterior to the ascending helix without active discharge, and a quiescent right post-incision wound. Preoperative blood work, renal and hepatic profiles, and chest radiography were within normal limits. The patient underwent simultaneous bilateral preauricular sinusectomy under general anesthesia using methylene blue tract delineation, elliptical skin incision, complete tract dissection with adjacent granulation removal, and primary closure over a small-calibre drain. Postoperative recovery was uneventful; the drain was removed on day three, sutures were removed on day ten, and the surgical wound remained quiescent without recurrence or hypertrophic scarring at the 39-day follow-up. Conclusion. Simultaneous single-stage bilateral sinusectomy combined with methylene blue tract delineation, prior infection control, and closed-system drainage produced excellent early outcomes in an adult with familial bilateral classic preauricular sinus.

Determinants of In-hospital Mortality in Preterm Neonates Admitted to a Tertiary Indonesian NICU: A One-Year Retrospective Cohort of 209 Infants Komang Okky Maharani Ciptana Putri; Putu Mas Vina Paramitha Cempaka; I Made Kardana; Made Sukmawati; Putu Junara Putra; I Wayan Dharma Artana
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1631

Background. Preterm birth is the largest single contributor to global neonatal mortality, and Southeast Asia carries a disproportionate burden, yet contemporary multivariable data from Indonesian tertiary neonatal intensive care units (NICUs) remain limited. We aimed to identify maternal, perinatal and neonatal determinants of in-hospital mortality among preterm neonates at the NICU of Prof. I.G.N.G Ngoerah Hospital, Denpasar, Bali. Methods. In a single-centre retrospective cohort, 209 preterm neonates (gestational age <37 weeks and birth weight <2500 g) admitted between September 2024 and September 2025 were enrolled by total sampling. Bivariate logistic regression with p<0.25 inclusion threshold was followed by multivariable binary logistic regression; intermediate-outcome variables (RDS and surfactant therapy) were excluded a priori to avoid over-adjustment bias. Results. In-hospital mortality was 42.1% (88/209) and decreased monotonically across birth-weight strata, from 75.0% in infants <1000 g to 41.9% in 1000–1499 g and 22.9% in ≥1500 g (Cochran–Armitage trend p<0.001). Sepsis (56.8%) and respiratory distress syndrome (30.7%) accounted for 87.5% of deaths. In the multivariable model, birth weight 1000–1499 g (adjusted odds ratio [aOR] 0.36, 95% CI 0.15–0.90; p=0.029) and ≥1500 g (aOR 0.17, 95% CI 0.06–0.51; p=0.001) and each 1-point increment in 5-minute Apgar score (aOR 0.81, 95% CI 0.67–0.98; p=0.031) were independently associated with lower mortality. Maternal urinary tract infection trended toward higher mortality (aOR 2.85, 95% CI 0.97–8.35; p=0.057). Conclusion. Birth weight and 5-minute Apgar score are independent, immediately measurable predictors of in-hospital preterm mortality in this Indonesian tertiary NICU. Combining bedside risk stratification with antenatal corticosteroid coverage audit and universal antenatal urine-culture screening offers a translational pathway to reduce neonatal mortality in resource-constrained Southeast Asian settings.

Incidence of Intraocular Inflammation, Retinal Vasculitis, and Retinal Vascular Occlusion Following Intravitreal Brolucizumab in Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis Ida Ayu Laksmi Devi; Sari Marina; Putu Daivi Prakriti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1632

Background. Brolucizumab is a humanized single-chain anti-VEGF antibody fragment licensed for neovascular age-related macular degeneration (nAMD). Post-marketing surveillance identified intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RVO) as adverse events of special interest, sometimes causing irreversible visual loss. Published incidence estimates range from below 1% to above 10%. We aimed to estimate the pooled cumulative incidence of these events and characterize heterogeneity drivers. Methods. PubMed/MEDLINE, Cochrane CENTRAL, and Google Scholar were searched for phase 3 randomized controlled trials (RCTs), phase IIIb prospective studies, and retrospective/registry studies (≥30 eyes) reporting IOI, RV, or RVO incidence after intravitreal brolucizumab 6 mg in nAMD. A DerSimonian–Laird random-effects model with Freeman–Tukey arcsine transformation was applied; REML, Paule–Mandel, and GLMM (logit link) estimators were used in sensitivity analyses. Results. Ten independent datasets (33,280 brolucizumab-treated eyes; 1,130 events) were included. Pooled cumulative incidence of any IOI/RV/RVO was 5.54% (95% CI 4.23–7.02%; I² = 94.0%; Q = 150.48). Prospective studies yielded higher pooled incidence (8.42%, 95% CI 4.12–14.04%) than retrospective/registry studies (4.35%, 95% CI 3.28–5.56%). Leave-one-out sensitivity ranged 4.98–6.19%. Funnel-plot asymmetry was detected (Egger t = 3.27; p = 0.011). More than 75% of events occurred within six months of the first injection. Conclusion. Cumulative incidence of IOI/RV/RVO after brolucizumab 6 mg in nAMD approached 5.5%, with markedly higher rates under independent adjudication. These findings support careful patient selection, baseline screening for prior IOI history, and intensified monitoring after brolucizumab initiation.

Occupational and Environmental Ultraviolet–Sunlight Exposure, Including Outdoor Agricultural Work, and the Risk of Cataract: A Systematic Review and Meta-Analysis of Observational Studies Kadek Diah Pramesti Ken Wardana; Sari Marina; Putu Daivi Prakriti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1633

Background.Cataract remains the leading cause of avoidable blindness worldwide, and occupational sunlight exposure is suspected as a modifiable risk factor among outdoor workers, including agricultural workers in tropical low- and middle-income countries (LMICs) such as Indonesia. Previous quantitative syntheses pooled mixed exposure-contrast metrics into a single estimate and obtained heterogeneity in excess of I2 = 95%, providing limited interpretable guidance for clinicians and policy makers. Methods.A systematic search of PubMed/MEDLINE was conducted and supplemented by citation tracing and translated search strings for Scopus, Embase, Web of Science and Cochrane CENTRAL. Eligible studies were observational analyses of adults reporting an OR, HR or relative risk with a 95% CI for occupational or environmental UV-sunlight exposure and cataract. Risk of bias was assessed using the Newcastle-Ottawa Scale. Effect estimates were pooled using DerSimonian-Laird random-effects models with REML and Hartung-Knapp-Sidik-Jonkman sensitivity estimators. Results.Seven observational studies (combined n approximately 60,000) met the inclusion criteria. Pooled OR from four extreme high-vs-low contrast studies: 6.52 (95% CI 4.12-10.33; I2 = 67%). Three modest per-unit/ever-vs-never studies pooled at OR/HR 1.09 (95% CI 1.04-1.14; I2 = 0%). The contrast-type moderator explained approximately 45% of between-study heterogeneity (p < 0.001). Conclusion.Occupational and environmental UV-sunlight exposure is associated with a clinically significant increase in cataract risk. The magnitude depended on the exposure contrast. The findings support targeted ocular-protection programmes for outdoor agricultural workers in high-insolation LMICs such as Indonesia.

Prophylactic Statin Therapy for the Prevention of Anthracycline-Induced Cardiotoxicity in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Cohort Studies Nadia Karimah Amalia; Yenny Dian Andayani; Mediarty; Norman Djamaludin
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1634

Background. Anthracycline-based chemotherapy remains a cornerstone of curative-intent breast-cancer treatment but carries a dose-dependent risk of cancer therapy-related cardiac dysfunction (CTRCD). Statins exert pleiotropic anti-inflammatory, antioxidative, and endothelial-stabilizing effects that may attenuate myocardial injury; however, prior meta-analyses pooled breast-cancer and lymphoma populations, obscuring breast-cancer-specific signals. Methods. A systematic review and random-effects meta-analysis was conducted per PRISMA 2020. PubMed, Cochrane, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) and propensity-matched cohort studies enrolling adult breast-cancer patients receiving anthracycline-based chemotherapy with or without trastuzumab. Co-primary outcomes were CTRCD incidence and standardized change in left-ventricular ejection fraction (LVEF, Hedges' g). Risk of bias was assessed using RoB 2.0 and ROBINS-I. Sensitivity analyses included leave-one-out exclusion and restriction to breast-cancer-only RCTs. Results. Ten studies (1,239 patients; six RCTs, four cohort studies) were included. The pooled risk ratio for CTRCD was 0.49 (95% CI 0.28–0.85; p = 0.011; I² = 0%). The pooled standardized mean difference for LVEF change was 0.38 (95% CI −0.06 to 0.81; I² = 81%), corresponding to approximately +2.1 LVEF percentage points. Sensitivity analyses restricted to breast-cancer-only RCTs strengthened the CTRCD effect (RR 0.36, 95% CI 0.16–0.82). HER2-positive subgroup analyses yielded a pooled RR of 0.28 (95% CI 0.10–0.80). Conclusion. Prophylactic statin therapy is associated with a clinically meaningful and statistically significant reduction in CTRCD in breast-cancer patients receiving anthracyclines. The protective effect is particularly pronounced in HER2-positive patients. A cautious, risk-stratified use of statins as a cardioprotective adjunct is supported pending adequately powered, breast-cancer-specific randomized trials.

Repeated Optical Biometry Failure as an Underrecognized Marker of Late In-the-Bag Intraocular Lens Decentration in Axial Myopia: A Case Report Angel Lim; Ni Made Dwipayani
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1636

Background: Late in-the-bag intraocular lens (IOL) dislocation is a delayed complication of cataract surgery driven by progressive zonular weakness, with axial myopia recognized as an independent risk factor. Its role as a hidden cause of optical biometry failure, however, has received little emphasis in the literature. Case presentation: A 58-year-old woman with longstanding axial myopia presented seven years after uneventful right-eye phacoemulsification with progressively blurred vision, monocular diplopia, and ghost images. Best-corrected visual acuity (BCVA) was 6/38 in the right eye improving to 6/15 with pinhole; refractometry revealed a new −4.00 D cylinder at axis 90° with persistent visual distortion consistent with irregular astigmatism. Slit-lamp examination showed inferior decentration of an in-the-bag posterior chamber IOL with a visible inferior haptic. Posterior segment evaluation through the displaced optic was hazy. Repeated optical biometry of the affected eye failed to acquire a valid axial-length signal across three sessions, whereas the fellow eye yielded reliable measurements. The patient was referred to a tertiary vitreoretinal center for IOL repositioning or exchange with possible pars plana vitrectomy and scleral fixation. Conclusion: In a myopic pseudophakic eye presenting with new-onset monocular diplopia and an astigmatic shift, repeated failure of optical biometry should be recognized as a critical diagnostic clue to underlying IOL instability, prompting timely tertiary referral and individualized surgical planning.

Intraoperative Incisional Wound Irrigation with 0.05% Chlorhexidine versus 0.9% Saline to Prevent Surgical Site Infection after Laparotomy for Hollow-Viscus Perforation Peritonitis: A Double-Blind Randomized Controlled Trial Oktova Ardianto; Bambang Am Am Setya Sulthana; Rizki Diposarosa
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1637

Background: Surgical site infection (SSI) is the most frequent complication of abdominal surgery and a major source of morbidity, prolonged hospitalization and cost, particularly in dirty (class IV) wounds created by gastrointestinal perforation; intraoperative incisional irrigation may lower wound bioburden, yet the optimal irrigant is undefined. Methods: We conducted a double-blind randomized controlled trial at a tertiary referral center in Bandung, Indonesia (November 2019–August 2020) comparing incisional irrigation with 0.05% chlorhexidine versus 0.9% saline in adults undergoing emergency laparotomy for hollow-viscus perforation peritonitis. After fascial closure, incisions were irrigated by allocation and patients were followed for 30 days, with superficial SSI (ASEPSIS score) as the primary outcome. Results: Of 141 patients screened, 96 were analyzed (49 chlorhexidine, 47 saline). Superficial SSI occurred in 5/49 (10.2%) chlorhexidine versus 14/47 (29.8%) saline patients (χ²=5.795, p=0.016; Fisher exact p=0.021; OR 0.268, 95% CI 0.088–0.818; relative risk 0.343; absolute risk reduction 19.6%; number-needed-to-treat 5.1). In multivariable logistic regression, chlorhexidine remained independently protective (adjusted OR 0.228, 95% CI 0.062–0.836, p=0.026), while intra-abdominal contamination (aOR 1.377 per 100 mL, p=0.008) and operative time (aOR 1.645 per 30 min, p=0.027) increased risk; the model discriminated well (AUC 0.835). No irrigation-related adverse events occurred. Conclusion: Incisional irrigation with 0.05% chlorhexidine markedly reduced superficial SSI after laparotomy for perforation peritonitis and offers a low-cost strategy for dirty abdominal wounds.

Efficacy and Safety of Adding Antiangiogenic Therapy to EGFR-Tyrosine Kinase Inhibitors versus EGFR-Tyrosine Kinase Inhibitor Monotherapy in EGFR-Mutant Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomised Controlled Trials Hermis Arsena; Sri Melati Munir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i7.1638

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) limits the durability of targeted therapy in EGFR-mutant non-small cell lung cancer (NSCLC). Inhibiting the vascular endothelial growth factor (VEGF) axis has been proposed to delay this resistance, but individual trials diverge and the antiangiogenic class has not been synthesised together across treatment settings. This study quantified the effect of adding antiangiogenic therapy to an EGFR-TKI on progression-free survival (PFS) and toxicity. Methods. Four databases were searched for randomised controlled trials (RCTs) comparing an EGFR-TKI plus an antiangiogenic agent (bevacizumab or ramucirumab) with the same EGFR-TKI alone in EGFR-mutant NSCLC. The pre-specified primary analysis was PFS in the first-line setting, expressed as the hazard ratio (HR) and pooled with an inverse-variance random-effects (DerSimonian-Laird) model; a restricted maximum-likelihood model confirmed it. Heterogeneity used I², τ² and a 95% prediction interval; risk of bias used Cochrane RoB 2.0. Results. Seven RCTs (eight reports; 1,512 patients; six first-line, one second-line) were included. In the six first-line trials the combination prolonged PFS (pooled HR 0.61, 95% CI 0.53-0.70; p<0.0001) with no heterogeneity (I²=0%; prediction interval 0.50-0.74); the restricted maximum-likelihood estimate was identical. The benefit was consistent for bevacizumab (HR 0.62, 0.52-0.73) and ramucirumab (HR 0.59, 0.46-0.76), a mean prolongation of median PFS of about 5.5 months. Adding the second-line osimertinib/T790M trial attenuated the effect (HR 0.66, 0.56-0.77; I²=32%), driven by absence of benefit in that setting (HR 0.96). Leave-one-out estimates were stable (0.59-0.63); the Egger test was non-significant. Grade ≥3 adverse events were increased (risk ratio 1.95, 1.47-2.57; absolute increase about 29 percentage points; number needed to harm about 4). Conclusion. Adding antiangiogenic therapy to a first-line EGFR-TKI consistently prolongs PFS in EGFR-mutant NSCLC as a VEGF-pathway class effect, at the cost of roughly doubled severe toxicity and without a demonstrated overall-survival gain. The benefit was not evident in the second-line osimertinib/T790M setting, suggesting the strategy delays rather than overcomes resistance.

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