Critical Reviews in Oncology Hematology

Article	Citations
Harnessing tumor metabolism during cancer treatment: A narrative review of emerging dietary approaches	261
Comparative efficacy of first-line therapies for PD-L1-negative advanced NSCLC: A network meta-analysis with reconstructed survival curves	175
Microbiome and lung cancer: carcinogenic mechanisms, early cancer diagnosis, and promising microbial therapies	138
The role of cGAS-STING in remodeling the tumor immune microenvironment induced by radiotherapy	128
Systemic immune-inflammation index as a predictor of survival in non-small cell lung cancer patients undergoing immune checkpoint inhibition: A systematic review and meta-analysis	125
Current status of locally advanced rectal cancer therapy and future prospects	102
Development of treatment strategies for advanced HER2-positive gastric cancer: Insights from clinical trials	99
Tyrosine kinase inhibitors in cancers: Treatment optimization – Part II	87
A non-invasive miRNA-based approach in early diagnosis and therapeutics of oral cancer	85
Stereotactic body radiotherapy as an alternative to brachytherapy in cervical cancer (SCORE): A systematic review and meta-analysis	77
Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study	76
Double agents in immunotherapy: Unmasking the role of antibody drug conjugates in immune checkpoint targeting	73
Apigenin in cancer prevention and therapy: A systematic review and meta-analysis of animal models	73
Microbiome dynamics in breast cancer: Mechanisms, therapeutic impacts and research gaps	71
Novel bioengineered drugs with immunotherapies for malignant pleural effusion: Remodulate tumor immune microenvironment and activate immune system	70
Real-world analysis of primary central nervous system diffuse large B-cell lymphoma	65
Advancing tumor vaccines: Overcoming TME challenges, delivery strategies, and biomaterial-based vaccine for enhanced immunotherapy	64
Novel insight into the Warburg effect: Sweet temptation	61
Direct and indirect effects on child neurocognitive development when maternal cancer is diagnosed during pregnancy: What do we know so far?	60
Open issues in the therapeutic management of unresectable stage III NSCLC in the immunotherapy era	58
Hurrying up but not rushing, acting and not reacting, good sense and not common sense: Open thoughts and reasonable doubts on COVID-19 vaccination strategies in cancer patients	54
Instruments and scales for the evaluation of acute radiation dermatitis: A systematic review	53
Editorial Board	49
Surface-Enhanced Raman Scattering (SERS) combined with machine learning enables accurate diagnosis of cervical cancer: From molecule to cell to tissue level	46
Letter to the Editor regarding the article “A net-work meta-analysis of the cardiac safety for next-generation hormonal agents in treating castration-resistant prostate cancer: How to choose drugs app	46

Mapping the research landscape of HPV-positive oropharyngeal cancer: a bibliometric analysis	45
Stereotactic body radiation therapy versus conventional external beam radiation therapy for painful bone metastases: A systematic review and meta-analysis of randomized trials	43
Unveiling the Role of JAK2/STAT3 signaling in chemoresistance of gynecological cancers: From mechanisms to therapeutic implications	42
Efficacy of PD-1/PD-L1 immunotherapy on brain metastatic non-small-cell lung cancer and treatment-related adverse events: A systematic review	41
The cytokines in tumor microenvironment: from cancer initiation-elongation-progression to metastatic outgrowth	40
A bone paradigm challenging the standard model of myeloma oncogenesis	40
Navigating management of localized prostate cancer in the geriatric population	40
Skin barrier dysfunction in cutaneous T-cell lymphoma: From pathogenic mechanism of barrier damage to treatment	39
Total neoadjuvant treatment and organ preservation strategies in the management of localized rectal cancer: A narrative review and evidence-based algorithm	39
Dysregulation of systemic immunity in colorectal cancer and its clinical applications as biomarkers and therapeutics	39
Innovations in cancer immunotherapy: A comprehensive overview of recent breakthroughs and future directions	39
UGT1A1 Testing in Breast Cancer: should it become routine practice in patients treated with antibody-drug conjugates?	38
Optimal treatment strategy for central nervous system non-germinomatous germ cell tumors: A systematic review and meta-analysis	38
Comparative analysis of systemic treatment with or without immune checkpoint inhibitors for advanced or recurrent endometrial cancer: A systematic review and meta-analysis of randomized controlled tri	37
First-line treatments for advanced or recurrent endometrial cancer: Systematic literature review of clinical evidence	36
Comment on “The risk of breast cancer and gynecologic malignancies after ovarian stimulation: Meta-analysis of cohort study”	35
Editorial Board	34
TIGIT: Will it be the next star therapeutic target like PD-1 in hematological malignancies?	34
Impact of immune cells on the hallmarks of cancer: A literature review	34
Editorial Board	33
Management of secondary immunodeficiency in hematological malignancies in the era of modern oncology	33
Cellular and molecular mechanisms implicated in the dual role of ROR2 in cancer	33
KRAS mutated colorectal cancers with or without PIK3CA mutations: Clinical and molecular profiles inform current and future therapeutics	33
Immuno-oncology therapy in metastatic bladder cancer: A systematic review and network meta-analysis	32
ESO's career development program (2002-2021): Presentation and evaluation	32
Neoadjuvant therapy for muscle-invasive bladder cancer: Current clinical scenario, future perspectives, and unsolved questions	32
Can inflammasomes promote the pathophysiology of glioblastoma multiforme? A view about the potential of the anti-inflammasome therapy as pharmacological target	32
Chemotherapy, immunotherapy, and targeted therapy for osteosarcoma: Recent advancements	31
Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for gastric cancer with peritoneal metastases: A systematic review by the PIPAC UK collaborative	31
Advantages and drawbacks of dexamethasone in glioblastoma multiforme	31
Immunotherapy in OSCC: Current trend and challenges	30
Predictive factors for return to work among cancer survivors in Europe: A systematic review	30
Effect of exercise on functional capacity in patients with advanced cancer: A meta-analysis of randomized controlled trials	29
Targeting hypoxia-inducible factor pathways in sporadic and Von Hippel-Lindau syndrome-related kidney cancers	29
Platelet-mediated tumor metastasis mechanism and the role of cell adhesion molecules	29
Clinical trials for patients with salivary gland cancers: A systematic review of worldwide registers and an evaluation of current challenges	28
The biology and treatment of leiomyosarcomas	28
Thrombosis and cachexia in cancer: Two partners in crime?	28
Exosomes derived from cancer-associated fibroblasts mediate response to cancer therapy	28
Next-generation immunotherapy in relapsed/refractory multiple myeloma: Strategies to achieve sustained MRD negativity	28
Efficacy and safety of targeted therapy and immunotherapy in advanced vulvar squamous cell carcinoma: A scoping review	27
CAR T-cell therapy landscape in pediatric, adolescent and young adult oncology – A comprehensive analysis of clinical trials	27
Unveilling the potential of liquid biopsy in pancreatic cancer for molecular diagnosis and treatment guidance	27
Minimal residual disease testing for classical Hodgkin lymphoma: A comprehensive review	27
The extracellular matrix in colorectal cancer and its metastatic settling – Alterations and biological implications	26
Challenges facing CAR T-cell immunotherapy in multiple myeloma	26
The peripheral tumor neuro-microenvironment: Deciphering neural landscape and mechanistic insights for therapeutic innovation	26
Efficacy of stereotactic radiosurgery as single or combined therapy for brain metastasis: A systematic review and meta-analysis	26
Synergistic effects of immunotherapy and adjunctive therapies in prostate cancer management	26
Unlocking the potential of Molecular Tumor Boards: from cutting-edge data interpretation to innovative clinical pathways	26

Quantifying absolute benefit for adjuvant treatment options in renal cell carcinoma: A living interactive systematic review and network meta-analysis	26
Unraveling molecular mechanisms of head and neck cancer	26
The role and clinical significance of tumor-draining lymph nodes in tumor progression and immunotherapy	25
Antibody-oligonucleotide conjugates in cancer therapy: Potential and Promise	25
The role of liquid biopsy in epithelial ovarian cancer: State of the art	25
The role of central nervous system (CNS) prophylaxis in preventing DLBCL patients from CNS relapse: A network meta-analysis	25
Prognostic scores including peripheral blood-derived inflammatory indices in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors	25
DLL3 as a potential diagnostic and therapeutic target in neuroendocrine neoplasms: A narrative review	25
Bone health in glucocorticoid-treated childhood acute lymphoblastic leukemia	25
Strategies to overcome chemoresistance in epithelial ovarian cancer: Navigating beyond challenges	24
A comprehensive review on targeting diverse immune cells for anticancer therapy: Beyond immune checkpoint inhibitors	24
Epigenetic-modifying agents: The potential game changers in the treatment of hematologic malignancies	24
Targeting TIME in advanced hepatocellular carcinoma: Mechanisms of drug resistance and treatment strategies	24
« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review	24
RNA N4-acetylcytidine modification in gastrointestinal cancer: Novel functions, mechanisms, and therapeutic implications	23
Recent advances and research progress in biomarkers for chronic graft versus host disease	23
Towards a new approach in pleural mesothelioma: Perioperative immunotherapy and its implications	23
Systematic review of tumour budding and association with common mutations in patients with colorectal cancer	23
The association between paraneoplastic neurological syndromes (PNS) and urothelial carcinoma – A review of the literature	23
Role of radiation in chimeric antigen receptor T-cell therapy for patients with relapsed/refractory non-Hodgkin lymphoma: Current studies and future prospects	22
Receptor status of breast cancer diagnosed during pregnancy: A literature review	22
Pathology, immunosuppression and NK cell immunotherapy of non-small cell lung cancer	22
Editorial Board	22
Personalized medicine for metastatic prostate cancer: The paradigm of PARP inhibitors	22
Facing the climate change: Is radiotherapy as green as we would like? A systematic review	22
Salvage radiotherapy after initial cryotherapy for localized prostate cancer: A systematic review of the literature	22
Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers	22
Plasmonic surgery: SERS-active smart nanotools reshaping intraoperative decision-making and precision therapy	21
Unlock the code of MHC II-enabled Cancer immunotherapy	21
Cardio-oncology concerns in radiotherapy: Heart and cardiac substructure toxicities from modern delivery techniques	21
Rethinking treatment paradigms: Neoadjuvant therapy and de-escalation strategies in HPV-positive head and neck cancer	21
Safety and efficacy of liposomal irinotecan as the second-line treatment for advanced pancreatic cancer: A systematic review and meta-analysis	21
Recent development in bispecific antibody immunotherapy for hematological malignancies	21
Long-term strategies for management of advanced basal cell carcinoma with hedgehog inhibitors	20
Decoding the puzzle: A multidisciplinary systematic review of adult brainstem glioma	20
Drug-based therapy for advanced adenoid cystic carcinoma: Current landscape and challenges based on an overview of registered clinical trials	20
Combining gut microbiota modulation and immunotherapy: A promising approach for treating microsatellite stable colorectal cancer	20
Sialylated glycoproteins and sialyltransferases in digestive cancers: Mechanisms, diagnostic biomarkers, and therapeutic targets	20
Revolutionizing immunotherapy: The next frontier in CAR T-cell engineering	20
The crosstalk of the human microbiome in breast and colon cancer: A metabolomics analysis	19
Rare histotypes of epithelial biliary tract tumors: A literature review	19
Delta-like ligand 3 in small cell lung cancer: Potential mechanism and treatment progress	19
Association between bevacizumab with cancer drug therapies and drug-induced interstitial lung disease in patients with solid tumor: A systematic review and meta-analysis of randomized clinical trials	19
Androgen annihilation versus advanced androgen blockage as first line treatment for metastatic castration resistant prostate cancer: A systematic review and meta-analysis	19
Endometrial cancer in the elderly: Characteristics, prognostic and risk factors, and treatment options	19
Testicular germ cell tumors: Genomic alternations and RAS-dependent signaling	19
The relationship between LDH and GLIM criteria for cancer cachexia: Systematic review and meta-analysis	19
Evaluation of clinical decision support systems in oncology: An updated systematic review	19
IHC-based molecular classification in muscle-invasive urothelial bladder carcinoma: Prognostic and predictive value toward a clinically applicable IHC marker panel – A systematic review	19
Artificial intelligence: A promising frontier in bladder cancer diagnosis and outcome prediction	19
Role of innate immunity in tumor microenvironment of HPV-associated anal cancer: The hypothetical beneficial role of γδ T cells.	19
Incidence of antibody–drug conjugates-related pneumonitis in patients with solid tumors: A systematic review and meta-analysis	19
Deciphering the possible reciprocal loop between hepatic stellate cells and cancer cells in the tumor microenvironment of the liver	19
Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?	19
Next-Generation models of Gallbladder Carcinoma: Linking biological insights to precision medicine	19
Navigating chemotherapy and immunotherapy in early-stage lung cancer. A critical review and statements from INTERACTION group	19
Elucidating the mechanistic role of ovarian cancer biomarkers: Lessons learnt from affinity-proteomics	18
N6-methyladenosine-dependent signaling in colorectal cancer: Functions and clinical potential	18
Combine radiotherapy and immunotherapy in esophageal squamous cell carcinoma	18
Circular RNAs as key regulators in cancer hallmarks: New progress and therapeutic opportunities	18
Radiosensitization strategies for hepatocellular carcinoma: Mechanisms, therapeutic advances, and clinical perspectives	18
Anticancer mechanisms and applications based on γδ T cells in cancer immunotherapy	18
The impact of survivorship bias in glioblastoma research	18
Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer	18
Clonal hematopoiesis of indeterminate potential (CHIP): A potential contributor to lymphoma	18
Targeting breast cancer stem cells through retinoids: A new hope for treatment	18
Is it a new era for intrahepatic cholangiocarcinoma?	18
Current landscape of hypoxia in thyroid cancer pathogenesis and treatment	17
Radiotherapy of high-grade gliomas: dealing with a stalemate	17
A scoping review to map the evidence of physical activity interventions in post-treatment adolescent and young adult cancer survivors	17
The diagnostic accuracy of single-item scales in detecting fatigue in patients with cancer: A systematic review and meta-analysis	17
Uncovering the bookshelves of CRISPR-based libraries: Advances and applications in cancer studies	17
Symptomatologic outcomes of gut microbiota modifiers (probiotics, prebiotics and synbiotics) in cancer care: A scoping review of randomized controlled trials	17
Molecular oncology of iodine refractory thyroid cancer current therapies and perspective	17
Molecular mechanisms of ferroptosis and its role in prostate cancer therapy	17
Immune checkpoint inhibitors as a threat to reproductive function: A systematic review	17
Cardiovascular safety outcomes of chronic lymphocytic leukemia treatments: A systematic and targeted literature review	16
Stereotactic body radiotherapy boost as an alternative to brachytherapy for cervical cancer: A scoping review	16
Metaplastic breast cancer: A review	16
The application of stepped-wedge cluster-randomized controlled trial study designs in oncology settings: A systematic review	16

Effect of non-pharmacological interventions on symptoms and quality of life in patients with hematological malignancies – A systematic review	16
Safety assessment of antibody-drug conjugates: Nonclinical toxicology, non-active ingredients, and environmental risk considerations	16
A neuroendocrine biomarker revolution from monoanalyte to multianalyte biomarkers in non-functioning gastro-entero-pancreatic neuroendocrine neoplasms	16
Editorial Board	16
Outcome after treatment with axitinib in children, young adults, and adults with renal cell carcinoma: a narrative review	16
COVID-19 and immunothrombosis: Pathophysiology and therapeutic implications	16
Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer	15
Extrachromosomal DNA in cancer: Molecular mechanisms underlying oncogene amplification and tumor heterogeneity	15
KRAS G12C-mutant driven non-small cell lung cancer (NSCLC)	15
Management of patients with extensive small-cell lung cancer in the immunotherapy era: An Italian consensus through a Delphi approach	15
Status of breast cancer in Latin American: Results of the breast cancer revealed initiative	15
Significance of HOXD transcription factors family in progression, migration and angiogenesis of cancer	15
Spatial transcriptomics in pancreatic cancer: Advances, prospects and challenges	15
Fatty acid in the tumor microenvironment: Perspectives for immunotherapy	15
Tyrosine kinase inhibitors in cancers: Treatment optimization – Part I	15
Expanding horizons in cancer therapy by immunoconjugates targeting tumor microenvironments	15
Chimeric antigen receptor T cell immunotherapy for gynecological malignancies	15
CD200 expression in hematopoietic neoplasms: Beyond a marker for diagnosis of B-cell neoplasms	15
The educational contribution of the college of the European school of oncology (ESCO): A survey analysis of the first three years	15
The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: the challenge is open for new therapeutic st	15
Radioprotective agents against the ionizing radiation-induced hematopoietic stem and progenitor cell injury; Foundation review	15
Targeting the DNA damage response: PARP inhibitors and new perspectives in the landscape of cancer treatment	15
WEE1 inhibition in cancer therapy: Mechanisms, synergies, preclinical insights, and clinical trials	15
Evidence-based recommendations for induction and maintenance treatment of newly diagnosed transplant-ineligible multiple myeloma patients	15
Additions and subtractions of radiotherapy in patients with oligometastatic non-small cell lung cancer under the era of immunotherapy	15
Targeting the DNA damage response to enhance radiotherapy in soft tissue sarcomas	14
Cardiac and vascular toxicity of amivantamab in non-small cell lung cancer (NSCLC): A systematic review	14
Exploring the molecular interactions between ferroptosis and the Wnt/β-catenin signaling pathway: Implications for cancer and disease therapy	14
Polyploid giant cancer cells: Underlying mechanisms, signaling pathways, and therapeutic strategies	14
Epidermal growth factor receptor exon 20 insertion variants in non-small cell lung cancer patients	14
Editorial Board	14
Profile of treatment-related adverse events of PD-1 blockade-based therapies in advanced esophageal cancer: A systematic review and meta-analysis	14
Evolving treatment for advanced non-small cell lung cancer harbouring common EGFR activating mutations	14
The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study	14
HER2-targeted therapies: Unraveling their role in biliary tract cancers	14
Factors for a broad technology assessment of comprehensive genomic profiling in advanced cancer, a systematic review	14
Which is the best treatment for melanoma brain metastases? A Bayesian network meta-analysis and systematic review	14
The current landscape of systemic therapy for recurrent glioblastoma: A systematic review of randomized-controlled trials	14
Venous thromboembolism in cancer and cancer immunotherapy	14
Somatic and germline ATM variants in non-small-cell lung cancer: Therapeutic implications	14
Gamma Knife radiosurgery as primary treatment of low-grade brainstem gliomas: A systematic review and metanalysis of current evidence and predictive factors	14
The role of the SIX family in cancer development and therapy: Insights from foundational and cutting-edge research	14
Protective effects of physical activity in colon cancer and underlying mechanisms: A review of epidemiological and biological evidence	14
The effects of race on anti-PD-(L)1 monoclonal antibodies in non-small cell lung cancer: A systematic literature review and meta-analysis	14
Patients’ selection and trial matching in early-phase oncology clinical trials	14
Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies	14
The effect of COVID-19 pandemic on daily oncology clinical practice	14
The roles of immune cells and non-immune cells in pre-metastatic niche of breast cancer	14
The impact of PARP inhibitors in the whole scenario of ovarian cancer management: A systematic review and network meta-analysis	14
Neoadjuvant endocrine therapy for luminal breast tumors: State of the art, challenges and future perspectives	14
Long non-coding RNAs as immune landscape regulators in cancer: A spotlight on HEIH in immuno-oncology	14
Diagnosis and treatment of therapy-related acute myeloid leukemia	14
Application of molecular imaging in immune checkpoints therapy: From response assessment to prognosis prediction	13
Belgian expert consensus for tumor-agnostic treatment of NTRK gene fusion-driven solid tumors with larotrectinib	13
How safe and effective is irradiating radiation-induced meningiomas? Single-center experience in primary and salvage Gamma-Knife Radiosurgery, systematic review, and metanalysis of current evidence on	13
Perioperative imaging predictors of tumor progression and pseudoprogression: A systematic review	13
International consensus on the initial diagnostic workup of cancer of unknown primary	13
Epigenetics in advanced renal cell carcinoma: Potential new targets	13
Is antibody-drug conjugate a rising star for clinical treatment of solid tumors? A systematic review and meta-analysis	13
Real-world insights into the efficacy and safety of tyrosine kinase inhibitors against thyroid cancers	13
KRAS mutations in advanced non-small cell lung cancer: From biology to novel therapeutic strategies	13
Warming-up the immune cell engagers (ICEs) era in breast cancer: state of the art and future directions	13
Advancements in tumor-infiltrating lymphocytes: Historical insights, contemporary milestones, and future directions in oncology therapy	13
The prevalence of solid tumors and hematologic malignancies among patients with Down syndrome: A systematic review and meta-analysis	13
Advancing patient setup: A comprehensive scoping review of tattoo-less techniques in radiation therapy	13
Erratum to “Beyond the blood-brain barrier: Intranasal vaccines in cancer immunotherapy” [Crit. Rev. Oncol./Hematol. 216C (2025) 104938]	13
Editorial Board	13
Clonal hematopoiesis and inflammation: A review of mechanisms and clinical implications	13
Safety of immune checkpoint inhibitors: An updated comprehensive disproportionality analysis and meta-analysis	13
Comment on “A systematic review and meta-analysis of PD-1/PD-L1 inhibitors in specific patient subgroups with advanced gastro-oesophageal junction and gastric adenocarcinoma”	13
The application of cancer stem cell model in malignant mesothelioma	13
Unlocking the intricacies: Exploring the complex interplay between platelets and ovarian cancer	13
Relationship between purinergic signalling and oxidative stress in prostate cancer: Perspectives for future therapy	13
Surrogate endpoints in phase III randomized trials of advanced gastroesophageal cancer: A systematic review and meta-analysis	12
Transarterial radioembolization in neuroendocrine liver metastases 25 years later: A systematic review	12
Insights into Sorafenib resistance in hepatocellular carcinoma: Mechanisms and therapeutic aspects	12
Small cell lung cancer unveiled: Exploring the untapped resource of circulating tumor cells-derived organoids	12
Long non-coding RNA and the tumor microenvironment: Prospects for clinical applications in breast cancer	12
Which treatment after first line therapy in NSCLC patients without genetic alterations in the era of immunotherapy?	12
Corrigendum to “The emerging HER2 landscape in Colorectal Cancer: The key to unveil the future treatment algorithm?” [Crit. Rev. Oncol./Hematol. 204 (2024) 104515]	12
Key considerations for a prostate cancer mRNA vaccine	12
Optimizing management of cutaneous toxicities from amivantamab in first-line non-small cell lung cancer: A clinical perspective	12
Cellular senescence in tumor immune escape: Mechanisms, implications, and therapeutic potential	12
The role of PIK3CA mutation in lobular breast cancer in the era of precision oncology – A systematic review	12
HER2-low breast cancer: Novel detections and treatment advances	12
Optimizing CDK4/6 inhibitors in advanced HR+/HER2- breast cancer: A personalized approach	12
Advanced and recurrent endometrial cancer: State of the art and future perspectives	12
Prediction performance of twelve tumor mutation burden panels in melanoma and non-small cell lung cancer	12
Liquid biopsy and preclinical tools for advancing diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms	12
Clinical implications of the Drug-Drug Interaction in Cancer Patients treated with innovative oncological treatments	12
The potential of circulating cell-free RNA in CNS tumor diagnosis and monitoring: A liquid biopsy approach	12
Head and neck squamous cell carcinoma: Exploring frontiers of combinatorial approaches with tyrosine kinase inhibitors and immune checkpoint therapy	12
Differentiation therapy: Unlocking phenotypic plasticity of hepatocellular carcinoma	12
Bladder-sparing treatment for muscle-invasive bladder carcinoma using immune checkpoint inhibitors	12
Prognostic and therapeutic potential of STAT3: Opportunities and challenges in targeting HPV-mediated cervical carcinogenesis	12