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All Journal MEDIA MEDIKA INDONESIANA Journal of Nutrition and Health JURNAL GIZI INDONESIA Jurnal Kedokteran Diponegoro Journal of Nutrition College Sari Pediatri Molecular and Cellular Biomedical Sciences (MCBS) Jurnal Riset Kesehatan Poltekkes Depkes Bandung Bioscientia Medicina : Journal of Biomedicine and Translational Research Medica Hospitalia World Nutrition Journal IJCNP (INDONESIAN JOURNAL OF CLINICAL NUTRITION PHYSICIAN) Diponegoro International Medical Journal (DIMJ) Bioscientia Medicina : Journal of Biomedicine and Translational Research
Niken Puruhita
Clinical Nutrition Specialist Program, Faculty Of Medicine, Diponegoro University
Biochemistry, Genetics & Molecular Biology Dentistry Environmental Science Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Nursing Public Health

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Vitamin D in the Breast Cancer Continuum: A Systematic Review and Meta-Analysis of Primary Prevention, Patient Prognosis, and Adjunctive Treatment Response Felix Setiawan; Yan Wisnu Prajoko; Niken Puruhita; Aliva Nabila Farinisa
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (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.v10i1.1486

Abstract

Background: The role of vitamin D across the breast cancer spectrum remains complex and contested. Compelling preclinical antineoplastic mechanisms contrast with inconsistent clinical findings. Large randomized controlled trials (RCTs) show null effects for primary prevention, while observational studies often link higher vitamin D status at diagnosis with better prognosis. Key conflicts include this prevention-prognosis disconnect, debates over linear versus J-shaped prognostic dose-responses, and a "receptor-status paradox" where estrogen receptor-positive (ER-positive) disease shows prognostic links, but hormone receptor-negative (HR-negative)/triple-negative (TNBC) subtypes derive greater benefit (improved pathological complete response, pCR) from vitamin D intervention during neoadjuvant chemotherapy (NACT). This study systematically synthesizes evidence across these distinct clinical contexts. Methods: Following PRISMA guidelines, we systematically reviewed PubMed, EMBASE, and CENTRAL (January 1st, 2014–September 2nd, 2025) for high-impact RCTs and large prospective cohort studies evaluating vitamin D supplementation or serum 25-hydroxyvitamin D (25(OH)D) levels regarding breast cancer incidence, prognosis (survival/recurrence), or pCR after NACT. Quality was assessed (Cochrane RoB 2; Newcastle-Ottawa Scale). Data were extracted dually. Findings were synthesized stratigraphically (prevention, prognosis, treatment). A random-effects meta-analysis pooled pCR data from NACT RCTs. Results: Six high-quality studies (3 RCTs, 3 cohorts; N=31,026) were included. (1) Prevention: The VITAL RCT (N=25,871; mean baseline 25(OH)D 30.8 ng/mL) found no reduction in incident invasive breast cancer with 2000 IU/day vitamin D3 (HR 1.02, 95% CI 0.79–1.31). (2) Prognosis: Cohort studies (N=4,835) showed higher 25(OH)D linked to better OS (Adj HR T3 vs T1: 0.72). Complexity emerged: one study linked benefit specifically to ER-positive recurrence (Adj HR 0.87), while another reported a J-shaped curve for EFS, with worse outcomes at both low (≤52 nmol/L; Adj HR 1.63) and high (≥99 nmol/L; Adj HR 1.37) levels versus intermediate. (3) Treatment: Meta-analysis of two NACT RCTs (N=310) showed vitamin D supplementation significantly increased pCR rates (38.1% vs 22.6%; Pooled RR 1.69, 95% CI 1.21–2.36; P=0.002; I²=0%). Subgroup data strongly suggested greater benefit in HR-negative/TNBC and baseline-deficient patients. Conclusion: Vitamin D supplementation appears ineffective for primary breast cancer prevention in replete populations. Its prognostic role is complex, suggesting an optimal 25(OH)D range (potentially ~30-40 ng/mL) and possible ER-specific hormonal modulation effects, though causality from observational data remains uncertain. Critically, vitamin D intervention during NACT significantly improves pCR, particularly in HR-negative/TNBC, likely via distinct chemosensitization/immunomodulatory mechanisms. This synthesis provides a framework for understanding these context-dependent roles, supporting vitamin D assessment and potentially adjunctive NACT supplementation, especially in deficient patients with aggressive subtypes, pending necessary validation in larger trials.
Adaptive Radiotherapy (ART) versus Non-Adaptive IMRT for Locoregionally Advanced Nasopharyngeal Carcinoma: A Meta-Analysis of Dosimetric Advantages, Clinical Outcomes, and Organ-at-Risk Sparing Gina Amalia; Yan Wisnu Prajoko; Niken Puruhita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (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.v10i1.1488

Abstract

Background: Intensity-modulated radiotherapy (IMRT) is the cornerstone of treatment for nasopharyngeal carcinoma (NPC), offering high dose conformity. However, anatomical variations during the multi-week therapy course can compromise dosimetric accuracy. Adaptive radiotherapy (ART), which adjusts the treatment plan based on intra-treatment imaging, aims to mitigate these effects. This meta-analysis synthesized contemporary comparative evidence (2014–2025) on the efficacy and safety of ART versus non-adaptive IMRT in locoregionally advanced NPC. Methods: Following PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library were searched for studies comparing ART with non-adaptive IMRT (cohorts or hybrid/phantom plan comparisons) in locoregionally advanced NPC. Primary outcomes were locoregional recurrence-free survival (LRFS) and overall survival (OS); secondary outcomes included progression-free survival (PFS), distant metastasis-free survival (DMFS), and dosimetric metrics for targets (D98, Conformity Index [CI]) and organs-at-risk (OARs: parotid Dmean, spinal cord Dmax, brainstem Dmax). Hazard Ratios (HR) and Mean Differences (MD) were pooled using random-effects models. Data estimation methods (Tierney, Wan, Cochrane) were employed where necessary. Heterogeneity was assessed using I². Results: Nine studies (2 cohort, 7 dosimetric/anatomical) involving 362 patients (clinical) and 215 datasets (dosimetric) were included. ART significantly improved LRFS compared to non-adaptive IMRT (pooled HR = 0.53, 95% CI 0.32–0.88; I²=0%). No significant differences were found for OS (HR=0.98, 95% CI 0.64–1.50), PFS (HR=0.70, 95% CI 0.45–1.07), or DMFS (HR=0.88, 95% CI 0.48–1.62). Compared to hybrid/phantom plans, ART significantly enhanced target coverage (pooled PTV D98 MD = 2.15 Gy, 95% CI 1.10–3.20 Gy; I²=78%) and conformity (pooled CI MD = 0.05, 95% CI 0.02–0.08; I²=85%). ART significantly reduced OAR doses: parotid Dmean (pooled MD = -3.50 Gy, 95% CI -4.95 to -2.05 Gy; I²=90%), spinal cord Dmax (pooled MD = -3.95 Gy, 95% CI -5.80 to -2.10 Gy; I²=93%), and brainstem Dmax (pooled MD = -2.75 Gy, 95% CI -4.40 to -1.10 Gy; I²=91%). Dosimetric analyses exhibited high heterogeneity. Conclusion: ART significantly improves LRFS in locoregionally advanced NPC compared to non-adaptive IMRT. It provides substantial dosimetric advantages, enhancing target coverage and conformity while critically reducing doses to parotid glands, spinal cord, and brainstem. Despite high dosimetric heterogeneity and no demonstrated OS benefit, the improvements in LRFS and dose delivery support the thoughtful implementation of ART.
Co-Authors Adriyan Pramono Ahmad Syauqy Alfadila, Tsania Izza Aliva Nabila Farinisa Amalia Sukmadianti Amalia Sukmadianti Amriyatun - Annta Kern Annta Kern Nugrohowati Aryu Candra Asep Iwan Purnawan Asri Purwanti Banundari Rachmawati Budi Santosa Christianto, Febe Della Ayuning Priastiti Dewi, Suci Noviya Dian Ruspita Eiyta Ardinasari Enny Probosari Enny Probosari Ermia Edyanto Etika Ratna Noer Etisa Adi Murbawani Febe Christianto Febe Christianto FILLAH FITHRA DIENNY Gina Amalia Hagnyonowati Hagnyonowati Handayani, Endah Nur Hani Purnamasari Hartanto, Okky Heidi Listya Heri-Nugroho Heri-Nugroho Hermina Sukmaningtyas Hertanto Subagio Hertanto Wahyu Subagio Hertanto Wahyu Subagyo Hertanto WS JC Susanto Jennifer Setiawan Khairuddin - Kusmadewi Eka Damayanti Lilis Banowati Lisyani B Suromo Luciana Sutanto MARTHA ARDIARIA Martha Irene Kartasurya Minidian Fasitasari Muchlis Ahsan Udji Sofro Muhammad Sulchan Muhammad Sulchan Nadia Savitri Nathalia Safitri Noor Wijayahadi Noverita Rochsitasari Novitasari, Anggi Nugraheni Nugraheni Nurjanah, Ayu Nuryanto Nuryanto Puspito Arum Raysa Tanjung Sari Retnaningsih - Riwanto Rizkita, Maura Sania Rosa Kristiansen Saldi Fitra Setiawan, Felix SIGIT ADIANTO Siska Indah Septiana, Siska Indah Siti Fatimah Muis Siti Fatimah Muis Sofyan Harahap Sukma Paramita R, Sukma Suprihati - Tania Wijayanti Yan Wisnu Prajoko Yekti Wirawanni Yudomurti Yudomurti Yuniari, Dwi Zega Yudama Archilona