Search Results (3,423)

Background and Objectives: Although modern oncologic therapies have substantially improved cancer survival and overall prognosis, they have also led to an increasing burden of cardiovascular toxicity. Preventing severe complications such as heart failure and death remains a major priority, while maintaining the need for effective and potentially curative cancer therapy. Careful patient monitoring and early detection of cardiovascular complications may allow the timely implementation of cardioprotective strategies and treatments that could delay or prevent myocardial toxicity. Materials and Methods: A total of 92 women with breast cancer were enrolled in a prospective observational cohort study. All patients received an anthracycline-based chemotherapy regimen, cyclophosphamide, docetaxel and trastuzumab. Biomarker assessment, including NT-proBNP, high-sensitivity cardiac troponin I (hs-cTnI), Gal-3, and GDF-15, was performed at baseline and at the initiation of trastuzumab-based therapy. A comprehensive diastolic function assessment was performed, including transmitral Doppler flow parameters and tissue velocities. Patients were followed for 12 months, and all cardiovascular events occurring during the follow-up period were recorded. Results: Biological and ecocardiographic parameters were analyzed and multiple models of prediction were made. To identify predictors of estimated left ventricular filling pressure (eLVFP), stepwise multiple linear regression analyses were performed, and four significant predictors of left ventricular end-diastolic filling pressure were identified: one echocardiographic parameter (baseline LV filling pressure) and three biological variables (changes in Gal-3, GDF-15, and hs-cTnI levels after treatment). The overall regression model was highly significant (p < 0.001) and explained 77.07% of the variance in the dependent variable. Gal-3 was the strongest predictor of left ventricular filling pressure (p < 0.001). Conclusions: The regression analyses suggest that this phenotype is multifactorial, with echocardiographic indices capturing the functional component and circulating biomarkers reflecting complementary aspects of the underlying biological response. This multimodal approach may therefore help identify patients with early treatment-related cardiac changes and potentially those at increased risk of subsequent CTRCD, particularly during a period when conventional LVEF-based surveillance may still appear reassuring. Full article

Shear-wave time-of-flight (TOF) measurement enables controlled assessment of frequency-dependent wave propagation, but its feasibility in biological tissues remains insufficiently established. This study evaluated whether a custom shear-wave TOF device could detect frequency- and direction-dependent responses in ex vivo tissues. Three porcine liver samples and three chicken breast samples were examined. Chicken breast was measured with propagation parallel and perpendicular to visible muscle fibers. One-cycle sinusoidal excitations were applied at 40–160 Hz, with 50 acquisitions ensemble-averaged per sample–frequency measurement. TOF was estimated using Tx threshold detection and cumulative-energy-based Rx onset detection, and TOF-derived apparent shear-wave propagation speed was calculated from the Tx–Rx distance and the measured TOF. Frequency-dependent data were fitted using the Kelvin–Voigt fractional derivative model to obtain model-dependent KVFD fit parameters. Signal quality was assessed, and a preliminary descriptive comparison with HISKY EQTouch UD3000 (Wuxi Hisky Medical Technologies Co., Ltd., Wuxi, China) SWE was performed. All 63 averaged sample–frequency measurements satisfied the predefined primary-detection criteria. Mean apparent shear-wave speed was 3.145 m/s in porcine liver, 6.133 m/s in chicken breast measured parallel to the fibers, and 5.914 m/s in chicken breast measured perpendicular to the fibers, giving a parallel-to-perpendicular speed ratio of 1.037. Mean post-averaging, post-processing SNR ranged from 24.47 to 31.52 dB. The UD3000 comparison showed the same tissue ranking. The device detected frequency- and direction-dependent responses in averaged ex vivo signals, supporting its feasibility as a controlled research platform. Claims of absolute stiffness accuracy and intrinsic muscle anisotropy require independent calibration and validation. Full article

There is an increasing demand for ultrasound imaging technologies, particularly wearable and portable systems, for continuous physiological monitoring applications. Although some recent flexible ultrasound devices have adopted polymer encapsulations, typical rigid transducer designs still include metal housings and costly electrodes, contributing to increased device weight and fabrication cost. To address these limitations, we developed an aluminum-electrode/3D-printed polymer-housing ultrasound transducer (APUT) utilizing a polyvinylidene fluoride piezoelectric film. Compared to a gold-electrode/metal-housing ultrasound transducer, the APUT material costs and total weight were approximately 66% and 86% lower, respectively. Acoustic evaluation revealed a center frequency of 24.5 MHz and a fractional bandwidth of 60.9%, with axial and lateral resolutions of 51 and 152 μm, respectively. Furthermore, during a 3-h pulsed operation test, the APUT exhibited an initial increase in capacitance followed by a relatively stable response, with no progressive surface-temperature increase detected within the accuracy of the measurement method. Finally, successful ex vivo imaging of chicken breast tissue confirms the APUT’s biomedical applicability, highlighting its potential as a wearable, portable, and disposable ultrasound platform. Full article

Breast cancer (BRCA) possesses prominent molecular heterogeneity, where aberrant expression of genes annotated to asparagine metabolism networks drives malignant progression and therapeutic resistance. However, systematic construction of prognostic signatures from a holistic asparagine metabolic pathway perspective remains scarce, limiting the clinical translation of metabolic insights into prognostic tools. We integrated TCGA and GEO BRCA transcriptomic datasets to screen asparagine metabolism-related differentially expressed genes and build a prognostic model. Six biomarkers, SLC35A2, SRD5A2, NT5E, CEL, IFNG and CNR1, were selected via univariate Cox, LASSO and multivariate Cox regression. SRD5A2 and IFNG were enriched in low-risk patients, while the other four genes were upregulated in high-risk subgroups. This signature reliably stratifies patient prognosis, with risk scores correlating strongly with pathway activity, immune infiltration, immune checkpoints, mutation landscapes and drug responsiveness. Bioinformatic results were validated via TCGA cohort analysis, in vitro cellular assays and Western blot. Two in vivo models were established: 4T1 xenografts in 6-week-old BALB/c mice and DMBA/hormone-induced spontaneous breast tumors in 8-week-old SD rats. Tumors were generated by cell injection or DMBA gavage plus cyclic hormone treatment, and tissue sections were processed for immunohistochemistry. Consistent differential expression of the six core genes was validated across all in vitro and in vivo systems. In conclusion, this asparagine metabolism-associated signature offers candidate biomarkers for personalized prognosis and provides preclinical evidence for metabolism-targeted BRCA therapy. Full article

Triple-negative breast cancer (TNBC) is characterized by marked immune microenvironment heterogeneity and variable chemotherapy response, yet the epithelial transcriptional programs governing cytotoxic immune activation remain poorly understood. We performed an exploratory, integrative analysis using single-cell RNA sequencing of 31,962 cells from eight TNBC patients operationally stratified into Good and Bad Prognosis groups based on pathological lymphoid infiltration, a discovery grouping subsequently validated against pathological complete response (pCR) in three independent bulk RNA-seq cohorts. This analysis identified four epithelial transcriptional states. The G5 DNA damage subpopulation—predominantly restricted to Good Prognosis tumors (29.2% vs. 0%)—and the G4 Metabolism subpopulation—2.4-fold enriched in Bad Prognosis—were the primary prognostic signatures. Machine learning validation using nested leave-one-cohort-out (LOCO) cross-validation across 614 samples demonstrated that G4 + G5 raw genes with random forest yielded the largest observed mean AUC of 0.653, though these results are exploratory and do not establish a validated clinical classifier. CellChat ligand–receptor interaction analysis revealed that G5 DNA-damage epithelial cells are the dominant immune activators in Good Prognosis TNBC, predominantly engaging CD8 cytotoxic T cells through MHC-I antigen presentation via HLA-A/B/C/E/F → CD8A/CD8B interactions, the highest-probability signaling pathway identified. Spatial transcriptomics independently validated significantly higher DNA damage and CD8 T-cell scores in Good Prognosis tissue. Together, these exploratory findings suggest a framework in which tumor-intrinsic DNA damage signaling is associated with MHC-I antigen presentation upregulation and CD8 cytotoxic T-cell engagement, supporting further investigation of this axis and its potential implications for combining DNA-damaging chemotherapy with immune checkpoint blockade in TNBC. Full article

Background/Objectives: Triple negative breast cancer remains the most difficult breast cancer to treat as there are no specific targeted therapies. The tumor stroma is recognized as essential for the development of solid tumors. Cancer associated myofibroblasts are known to play a major role in the construction of a tumor microenvironment conducive to tumor progression. Therefore, we established a co-culture system to identify potential molecular targets controlling myofibroblast conversion. Methods: Co-cultures of MDA-MB-468 triple negative breast cancer cells and skin fibroblasts were either mixed prior to seeding or seeded individually on opposite sides of a culture dish and incubated in complete medium. Inhibitors were preincubated with cells for 1 h. Inflammatory cytokines were measured by ELISA. Proteins were analyzed using the Wes-Protein Simple System. Immunostaining was visualized using a Hamamatsu Photonics Nanozoomer. Statistical analysis was done by student’s t-test and one-way ANOVA. Results: The data indicate that co-culturing the cells promotes myofibroblast differentiation and cytokine release and this requires direct contact between the two cell types. Both myofibroblast conversion and cytokine release were prevented by inhibitors of TLR5, TGF-β and EDA-fibronectin. Conclusions: Data suggest that the TLR5 receptor on the MDA-MB-468 cells binds to EDA-fibronectin expressed by fibroblasts thus inducing inflammatory cytokine expression. Expression of EDA fibronectin is regulated through TGF-β whose synthesis is induced by TLR5 signaling in the tumor cells. The data are consistent with a model in which TLR5-mediated crosstalk between the cancer cells and the stromal fibroblasts creates a tissue microenvironment conducive to tumor growth and metastasis. Full article

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection and the primary etiological agent of cervical cancer. Despite the high global disease burden, the Middle East and North Africa (MENA) region faces substantial challenges in HPV prevention and control. This narrative review aimed to synthesize existing evidence on the prevalence, genotypic distribution, awareness, vaccination status, clinical outcomes, and the role of HPV in non-cervical malignancies in the MENA region. Methods: PubMed, Web of Science, Scopus, and Google Scholar were searched, and 122 studies were included. Findings were synthesized qualitatively and descriptively. Cohort studies, systematic reviews, and meta-analyses were prioritized to support inferences about associations and potential causal relationships. Results: HPV prevalence in the general female population of the MENA region ranged from 4.7% to 53.3%, exceeding 90% in high-risk groups and patients with malignancies. The most common genotypes were HPV16 and HPV18; however, distribution patterns varied across populations. Key risk factors included younger age, multiple sexual partners, early age at first sexual intercourse, smoking, and alcohol consumption. General awareness was low to moderate, and vaccination coverage was very low in most countries. Barriers included lack of knowledge, fear of side effects, religious concerns, and social stigma. Evidence also indicates an association between HPV and non-cervical malignancies (head and neck, esophageal, gastric, breast, and thyroid cancers), with HPV DNA detected in tumor tissues. Conclusions: HPV poses a significant public health challenge in the MENA region, characterized by high prevalence, genotypic diversity, limited knowledge and awareness, and unsatisfactory vaccination coverage. Expanding screening and vaccination through financial support, culturally and religiously appropriate education, and longitudinal studies to monitor genotypic changes and associations with other malignancies are essential measures to reduce the burden of HPV-related diseases in the region. Full article

To investigate the role and underlying mechanisms of TIMM8A in breast cancer progression. The expression of TIMM8A in breast cancer tissues and cell lines was assessed. Functional assays were performed to evaluate the effects of TIMM8A knockdown on proliferation, metastasis, and apoptosis in BT549 and MCF-7 cells. Co-immunoprecipitation (Co-IP) and ubiquitination assays were used to examine the interaction between TIMM8A and HSPA9, as well as the involvement of the E3 ubiquitin ligase RNF4. PI3K/AKT pathway activity was assessed by Western blotting. In vivo tumor growth was evaluated using a xenograft mouse model. TIMM8A was significantly upregulated in breast cancer tissues and cell lines, and high TIMM8A expression correlated with poor prognosis. TIMM8A knockdown suppressed proliferation and metastasis while inducing apoptosis in vitro. Mechanistically, TIMM8A interacted with HSPA9 and maintained its protein stability by inhibiting RNF4-mediated ubiquitination and degradation, thereby sustaining PI3K/AKT signaling activation. Conversely, TIMM8A depletion reduced HSPA9 stability and attenuated the pathway. Rescue experiments confirmed that HSPA9 overexpression restored PI3K/AKT activation and reversed TIMM8A-knockdown-induced malignant suppression. In vivo, TIMM8A silencing efficiently inhibited tumor growth, accompanied by reduced HSPA9 and Ki-67 expression and decreased PI3K/AKT phosphorylation. TIMM8A promotes breast cancer progression through the TIMM8A/HSPA9/PI3K/AKT regulatory axis, highlighting TIMM8A as a promising prognostic biomarker and potential therapeutic target for breast cancer. Full article

Cancer-associated thrombosis (CAT) is defined as venous or arterial thrombotic events occurring in patients with active malignancy or during anticancer treatment, most commonly presenting as venous thromboembolism and representing a leading cause of morbidity and mortality in oncology. Hormone-sensitive malignancies, including breast, ovarian, and endometrial cancers, are characterized by a complex interaction among tumor biology, endocrine signaling, inflammation, endothelial dysfunction, and coagulation activation. In these malignancies, venous thromboembolism (VTE) risk is influenced not only by intrinsic tumor-related mechanisms but also by patient-specific factors and anticancer therapies, particularly endocrine treatments, chemotherapy, targeted agents, and extensive surgical procedures. Breast cancer is generally associated with an intermediate thrombotic risk, although endocrine therapy—especially tamoxifen—significantly increases VTE incidence. Ovarian cancer represents one of the most thrombogenic solid tumors because of elevated tissue factor expression, inflammatory activation, advanced-stage presentation, and aggressive multimodal treatment strategies. Endometrial cancer exhibits a strong association with obesity, metabolic syndrome, prolonged estrogen exposure, and perioperative thrombotic complications. Emerging evidence highlights the role of immune-thrombosis, extracellular vesicles, inflammatory cytokines, and sex-specific coagulation pathways in cancer-associated hypercoagulability. Current guidelines increasingly support individualized thromboprophylaxis based on tumor biology, patient-specific risk factors, and bleeding risk assessment. This review summarizes the biological mechanisms linking hormones and thrombosis in breast and gynecologic cancers, discusses current evidence regarding VTE risk factors and treatment-related thrombotic complications, and explores modern approaches to biomarkers, risk stratification, and personalized thromboprophylaxis. Full article

MicroRNAs (miRNAs) have emerged as promising biomarkers for treatment response prediction in breast cancer. However, the role of circulating and tumour-derived miRNAs in predicting pathological complete response (pCR) following neoadjuvant therapy in HER2-positive (HER2+) breast cancer remains incompletely defined. To systematically evaluate the association between miRNA expression profiles and pCR in HER2+ breast cancer undergoing neoadjuvant systemic therapy, including chemotherapy with HER2-targeted agents. A systematic review of PUBMED, EMBASE, SCOPUS, and WEB OF SCIENCE databases was performed according to PRISMA guidelines. Studies evaluating circulating or tumour-derived miRNAs associated with pCR following neoadjuvant therapy in HER2+ breast cancer were included. Methodological quality was assessed using the QUIPS tool. Nine studies involving 937 HER2+ breast cancer patients were included. Overall, 39 unique miRNAs and four circulating miRNA signatures were associated with pCR outcomes. Seven studies evaluated circulating miRNAs, while two assessed tumour-derived miRNAs. The increased expression of six circulating miRNAs, four circulating signatures, and seventeen tumour-derived miRNAs was associated with pCR. Conversely, the increased expression of eleven circulating miRNAs and five tumour-derived miRNAs was associated with residual disease and non-pCR. MiR-210 was the only miRNA associated with response across more than one study, with an increased expression associated with residual disease in both circulating and tumour-derived analyses. Several circulating and tumour-derived miRNAs demonstrate potential as predictive biomarkers of pCR following HER2-targeted neoadjuvant therapy. However, substantial heterogeneity and limited validation currently restrict clinical implementation. Future prospective multicentre studies using standardised methodologies are required to clarify the role of miRNA profiling in personalised treatment strategies for HER2+ breast cancer. Full article

Background/Objectives: Contrast-enhanced mammography (CEM) has demonstrated high diagnostic accuracy in breast lesion detection and characterization. However, interpretation of enhancement intensity remains largely qualitative and subject to interobserver variability. This study aimed to evaluate the feasibility and reproducibility of a standardized region-of-interest (ROI)-based quantitative approach for enhancement assessment in CEM. Methods: In this single-center prospective study, 22 women undergoing CEM for suspicious findings on conventional breast imaging were enrolled, yielding a total of 27 lesions. Quantitative analysis was performed on recombined mediolateral oblique images acquired in both the early and delayed post-contrast phases. Three radiologists with different levels of experience independently performed ROI measurements using two standardized ellipsoidal ROI sizes (0.1 cm² and 0.2 cm²). ROIs were systematically positioned on the lesion, fibroglandular tissue, subcutaneous fat, and pectoralis major muscle. Relative ROI (rROI) metrics were calculated to reduce variability related to acquisition and post-processing factors. The primary normalized parameter was the lesion-to-parenchyma ratio (nROI). Histopathology served as the reference standard. Results: Of the 27 lesions, eight were benign (29.6%), eight were high-risk/B3 lesions (29.6%), and 11 were malignant (40.7%). Breast density categories were B in 11 lesions (40.7%), C in 13 lesions (48.1%), and D in three lesions (11.1%). Inter-reader reproducibility was good to excellent. Absolute lesion gray-scale values showed excellent agreement, with intraclass correlation coefficient (ICC) values ranging from 0.941 to 0.974, while nROI showed good reproducibility, with ICC values ranging from 0.861 to 0.894. No significant inter-reader differences were observed for normalized ratios. Comparison between ROI sizes showed small but statistically significant early phase differences for nROI, with median values of 1.009 for 0.1 cm² ROIs and 1.005 for 0.2 cm² ROIs (median paired difference −0.002; p = 0.002). Early phase nROI measured with the 0.1 cm² ROI differed significantly across breast density categories, increasing from density B to D (0.996, 1.010, and 1.015, respectively; p = 0.026). Conclusions: Standardized ROI-based quantitative analysis in CEM is feasible, and normalized enhancement ratios showed good inter-reader agreement, suggesting their potential to reduce variability related to subjective visual assessment and technical acquisition factors. Consequently, the proposed method provides a reproducible methodological framework for future larger studies aimed at validating quantitative CEM metrics. Full article

Background/Objectives: Lymphedema is a chronic condition caused by impaired lymphatic function that is characterized by fluid accumulation with progression to tissue thickening and fibrosis. Although various noninvasive assessment methods have been proposed, studies that have integrated fluid, structural, and stiffness-related changes are limited. To address this gap, we conducted an integrated multimodal assessment combining multiple-frequency bioelectrical impedance analysis (MFBIA), ultrasound tissue thickness measurements, and shear wave elastography (SWE) to characterize stage-specific changes in breast cancer-related lymphedema. Methods: This prospective cross-sectional study included patients who had undergone breast cancer surgery. Participants were classified into the clinical and subclinical lymphedema groups based on MFBIA criteria. Dermal thickness, subcutaneous thickness, and tissue stiffness measurements in both upper limbs were obtained using SWE on the same day. MFBIA parameters including extracellular water ratio, 5 kHz impedance ratio, and phase angle were assessed. Ipsilateral and contralateral limbs were compared, and correlation analyses of variables were performed. Results: Dermal thickness and subcutaneous thickness in the ipsilateral limb were greater than those in the contralateral limb in the overall cohort and subclinical group. Increased tissue stiffness measured using SWE was observed only in the clinical lymphedema group. MFBIA parameters in the clinical group were higher than those in the subclinical group. According to the correlation analysis, MFBIA parameters were associated with tissue thickness and SWE parameters were not correlated with other variables. Conclusions: These findings support the clinical utility of a multimodal approach for the stage-specific evaluation of breast cancer-related lymphedema, thereby facilitating stage-based and individualized management. Full article

Background/Objectives: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by multisystem infiltration of foamy histiocytes, leading to chronic inflammation, fibrosis, and organ dysfunction. Breast involvement in ECD is extremely uncommon, and the sonographic features of ECD involving the breast remain poorly described. Case Presentation: We report the case of a 59-year-old woman with chronic bone pain and multisystem disease who experienced an extended diagnostic course despite undergoing renal biopsy, biopsy of a right elbow lesion, bone marrow examination, and multidisciplinary evaluation. Breast ultrasound revealed bilateral infiltrative hypoechoic lesions involving the breasts and axillae. These were classified as BI-RADS 4C and were highly suspicious for breast malignancy. Subsequently, an ultrasound-guided core needle biopsy was performed on the breast and axillary lesions. Results: Histopathology showed fibroadipose tissue infiltrated by numerous foamy histiocytes, scattered epithelioid cells, and occasional Touton giant cells. Immunohistochemistry showed positivity for CD68, CD163, CD4, and Cyclin D1, partial positivity for OCT2 and CD30, and negativity for S100, CD1a, Langerin, ALK, CK (Pan), and GATA3. The Ki-67 index was approximately 3%. Molecular testing detected the BRAF V600E mutation, supporting the diagnosis of ECD. A review of reported cases showed that breast involvement in ECD lacks specific ultrasound findings and may closely mimic primary breast malignancy. Conclusions: Breast involvement in ECD is rare and may present as bilateral infiltrative hypoechoic lesions with axillary involvement on ultrasound. In patients with chronic bone pain, symmetric osteosclerosis, or multisystem disease, ECD should be considered in the differential diagnosis. Ultrasound-detected superficial lesions may provide accessible biopsy targets, helping to establish a timely diagnosis and reduce diagnostic delay. Full article

Feline mammary tumors are the third most common neoplasms in female cats and they are characterized by high aggressiveness and high metastatic rates. Given the pivotal role of iron in human breast cancer development, in this study, we preliminarily explore the immunohistochemical expression of proteins involved in iron uptake, storage and efflux [Transferrin Receptor 1 (TfR1), Transferrin Receptor 2 (TfR2), ferritin (FTH1), and ferroportin (SLC40A1)] in non-metastatic and metastatic feline mammary carcinomas and their tributary lymph node and the possible correlation with hypoxia-inducible factor-1 (HIF-1). Our results showed an increased expression of TfR1 and TfR2 in relation to tumor progression. FTH1 immunolabeling was mainly observed in cancer cells delimiting necrotic areas and in lymph node metastasis, indicating greater iron storage possibly associated with hypoxic environments, as suggested by increased expression of HIF-1α. Also, an increase in SLC40A1 labeling in tumoral cells suggested greater iron efflux. Although preliminary, our results underline interesting differences between feline normal and tumoral mammary tissues, which could pave the way to further in vitro studies to better understand the role of iron in the progression of feline mammary tumors. Full article

Background: A Phase I trial to study the efficacy and safety of MR-guided FUS-MB (focused ultrasound–microbubble) treatment combined with radiotherapy (RT) using a fully electronically MRI-guided steerable focused ultrasound system was performed. The investigation here carried out an exploratory quantitative analysis of images for the first ten participants who were treated with MRgFUS-MB therapy, identifying texture-based MRI features that changed significantly after treatment and indicating probable treatment-related changes in tumour morphology. Methods and Findings: Ten patients with stage I-IV breast cancer (Age: 64 ± 10.8) underwent 2 FUS-MB therapies throughout their radiation treatments, as deemed appropriate by a multidisciplinary team. MRI scans were performed prior to treatment and at 1- and 3-month follow-up. The tumours were segmented, and 2D and 3D features, including shape, first-order and texture features, were extracted for original and wavelet-filtered T1-weighted fat-saturated MR images. The overall significance of radiomic features in association with morphological changes in the target tumour over 1-month and 3-month follow-up in comparison to the first treatment day was investigated. Results: The five most significant features (p < 0.05) were selected using a sample-related t-test, out of which most features were wavelet-filtered first-order features. First-order wavelet-filtered robust mean absolute deviation (RMAD) emerged as the most consistent significant feature for both 2D and 3D features with sampled grid spacings of 0.5 mm and 1 mm. The volume of the tumour demonstrated a decline for 80% of patients over 3 months, as measured by the 3D mesh volume of the tumour ROI. There was a significant decline in tumour size and image heterogeneity, indicating plausible changes in the tumour microenvironment possibly related to the treatment. Conclusions: Previous preclinical studies and clinical evaluations have demonstrated the efficacy of MR-guided FUS-MB therapy. MRI image-based features from the T1-weighted MR scans over various follow-up times provide potential evidence of changes in tumour tissue heterogeneity that might be treatment-related. MRgFUS MB therapy can possibly evolve as a mode of radiotherapy enhancement in the future, which warrants further controlled validation. The availability of adequate data in the future might possibly lead to the identification of image biomarkers related to treatment response, thus providing better clinical evaluations. Full article