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Review Article | DOI: https://doi.org/10.31579/2640-1053/260
Department of Physics with electronics, Federal University Birnin Kebbi.
*Corresponding Author: Buhari Samaila., Department of Physics with electronics, Federal University Birnin Kebbi.
Citation: Buhari Samaila, (2026), Patient-Specific Risk Modeling of Radiation-Induced Secondary Malignancies Following Radiotherapy, J. Cancer Research and Cellular Therapeutics. 10(2); DOI:10.31579/2640-1053/260
Copyright: © 2026, Buhari Samaila. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 02 February 2026 | Accepted: 16 February 2026 | Published: 02 March 2026
Keywords: doctor-patient relationship; emotions; communicative interaction; cancer patient
Background: Radiotherapy (RT) remains a cornerstone of cancer management, offering substantial survival benefits across diverse malignancies. However, exposure to ionizing radiation confers long-term risks, notably radiation-induced secondary malignancies (RISM), particularly in younger patients and long-term survivors. Advances in treatment delivery have increased dose conformity but have also altered low-dose exposure patterns, necessitating robust patient-specific risk assessment frameworks. Contemporary research increasingly integrates physical dosimetry, biological response modeling, and computational techniques to estimate individualized secondary cancer risk.
Objective: This systematic review aimed to critically evaluate existing patient-specific modeling approaches used to estimate radiation-induced secondary malignancy risk following radiotherapy, with emphasis on dosimetric, biological, epidemiological, and data-driven frameworks, and to identify methodological gaps and future research priorities.
Methods: The review was conducted in accordance with PRISMA 2020 guidelines. Peer-reviewed studies published between 2009 and 2025 were systematically identified from major scientific databases. Eligible studies included original research, treatment-planning investigations, Monte Carlo simulations, systematic reviews, and modeling frameworks that quantitatively assessed secondary malignancy risk following photon, proton, or radionuclide radiotherapy. Data extraction focused on radiotherapy modality, modeling methodology, organ-specific risk estimates, and key findings. A qualitative synthesis was performed, categorizing studies by modeling domain and treatment technique.
Results: A total of 40 studies met the inclusion criteria. Dosimetric and physics-based modeling approaches, particularly Monte Carlo simulations, constituted the largest proportion of studies and consistently identified organ-specific absorbed dose and low-dose bath as dominant predictors of secondary cancer risk. Comparative analyses demonstrated that proton therapy reduced predicted secondary malignancy risk by approximately 40–60% compared with photon-based techniques across multiple disease sites. Epidemiological risk projection models revealed substantial inter-model variability, limiting precision at the individual patient level. Emerging biological models highlighted the role of radiation-induced lymphopenia and immune suppression as indirect modifiers of carcinogenesis, while machine-learning and radiomics-based models improved individualized risk stratification but lacked widespread external validation.
Conclusion: Patient-specific secondary malignancy risk following radiotherapy is governed by complex interactions between dose distribution, treatment modality, and biological susceptibility. While advanced modeling approaches have enhanced risk estimation, the absence of harmonized frameworks and long-term clinical validation limits routine clinical translation. Integrating dosimetric, biological, and data-driven models is essential for advancing precision radiotherapy and minimizing long-term radiation-related cancer risk.
Radiotherapy (RT) is a cornerstone in modern cancer management, providing curative or palliative benefits across a wide range of malignancies. Despite its clinical efficacy, exposure to ionizing radiation carries both acute and long-term risks, including systemic effects such as radiation-induced lymphopenia (RIL) and late sequelae such as secondary malignancies. RIL, characterized by substantial depletion of circulating lymphocytes, has emerged as a critical determinant of patient immune competence and therapeutic outcomes, with lymphocytes demonstrating extreme radiosensitivity even at low doses (Cella et al., 2024; De Kermenguy et al., 2025). Understanding and modeling RIL require an integrated consideration of patient-specific factors, treatment modalities, and dose distributions, as these influence both the severity and clinical implications of lymphocyte depletion. Concurrently, the risk of radiation-induced secondary cancers represents a major long-term concern, particularly in patients with favorable prognoses or younger age at initial treatment. Epidemiological and dosimetric studies indicate that secondary malignancy risk is highly dependent on treatment technique, irradiated volume, organ sensitivity, and cumulative dose to normal tissues. Comparative analyses demonstrate that proton therapy and advanced photon techniques such as volumetric modulated arc therapy (VMAT) or intensity-modulated radiotherapy (IMRT) can differentially impact organ-at-risk exposure, thereby influencing lifetime attributable risk of secondary cancers (Paganetti et al., 2020; Mazonakis et al., 2024; Zhang et al., 2020). Moreover, patient-specific factors, including genetic susceptibility, pre-existing comorbidities, and immune status, modulate both lymphopenia and carcinogenic risk, underscoring the necessity of individualized risk assessment. Modern research emphasizes the integration of dosimetric, biological, and computational modeling approaches to predict RT-induced toxicities. Voxel-based blood irradiation models, organ equivalent dose frameworks, and Monte Carlo simulations have advanced patient-specific risk prediction, allowing for the quantification of both in-field and out-of-field radiation effects (Timlin et al., 2015; Meyer et al., 2024; Kang et al., 2021). Such approaches facilitate the development of predictive nomograms and mechanistic models that inform clinical decision-making, optimize therapeutic ratios, and guide personalized treatment planning. Despite these advances, significant gaps remain, particularly regarding the harmonization of modeling frameworks, longitudinal validation of predicted risks, and inclusion of underrepresented populations in risk assessment studies (Paganetti, 2012; Shcherbakov et al., 2025). Collectively, these observations highlight a critical need for integrated, patient-specific, and multi-domain modeling approaches to evaluate both immediate and delayed RT-related toxicities. Systematic risk assessment frameworks that combine dosimetry, biological susceptibility, and patient-specific factors are essential for advancing precision radiotherapy, minimizing long-term complications, and enhancing clinical outcomes across diverse populations.
Methodology
Protocol and Registration
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review protocol was pre-defined to focus on patient-specific modeling approaches for radiation-induced secondary malignancies following radiotherapy, including both physical dosimetric models and biologically informed computational frameworks.
Information Sources and Search Strategy
The primary sources included peer-reviewed journals in radiation oncology, medical physics, and applied sciences. A total of 40 studies were identified and included for full-text review (Paganetti, 2009; König et al., 2020; Cella et al., 2024; etc.). Searches incorporated keywords and MeSH terms such as: “Radiotherapy AND secondary malignancy”, “Patient-specific risk modeling”, “Monte Carlo AND radiotherapy”, “Radiation-induced lymphopenia”, “Proton therapy AND secondary cancer”. No additional grey literature or conference abstracts were included to maintain methodological consistency and ensure data quality.
Eligibility Criteria
Studies were considered eligible if they met the following criteria:
Exclusion criteria included: editorials, letters, purely descriptive clinical reports without quantitative modeling, and studies that did not explicitly report on secondary cancer risk or patient-specific risk assessment.
Selection Process
Two independent reviewers screened all 40 identified studies using a two-step process. Initially, titles and abstracts were reviewed to exclude duplicates, irrelevant studies, and non-modeling papers, followed by a full-text assessment to confirm eligibility based on explicit patient-specific secondary malignancy modeling or mechanistic risk assessment. Any disagreements between reviewers were resolved through discussion, and consensus decisions were reached. The study selection process is presented in accordance with the PRISMA 2020 framework (Figure 1).
Figure 1: Study selection according to PRISMA 2020 framework
Data Extraction, Management and Risk of Bias Assessment
Data were extracted using a pre-designed table capturing: Author(s) and year, Country/location, Cancer site and procedure, Radiotherapy modality and methodology (including modeling approach), Quantitative findings (e.g., organ-specific dose, effective dose, predicted secondary cancer risk), and Key conclusions and identified gaps. All extracted data were cross-checked by a second reviewer for accuracy and completeness. Given the modeling-focused nature of the included studies, risk of bias was assessed using adapted criteria relevant for computational and treatment-planning studies. Parameters evaluated included: Appropriateness of dose distribution modeling, Consideration of out-of-field and organ-specific doses, Incorporation of biological or mechanistic parameters (e.g., lymphopenia, tissue heterogeneity), Validation against clinical or epidemiological data and Transparency and reproducibility of computational methods.
A qualitative synthesis of the included studies was performed, with investigations categorized according to radiotherapy modality (photon, proton, and radionuclide therapy), modeling approach (Monte Carlo, voxel-based, 3D tissue response, radiomics, machine learning, and immune/biological modeling), and cancer site-specific outcomes (breast, thoracic, pelvic, head and neck, craniospinal, and prostate). Where data allowed, comparative trends in predicted secondary malignancy risk were summarized across modalities, emphasizing the influence of dose distribution, tissue heterogeneity, and patient-specific biological factors on risk estimates. These structured comparisons provide insights into modality-dependent risk profiles and underscore the need for integrating dosimetric precision with biological and computational modeling to improve individualized risk assessment (König et al., 2020).
Characteristics of Included Studies
The studies included in this systematic review are summarized in Table 1. Collectively, they comprise modeling studies, treatment-planning investigations, systematic reviews, retrospective cohort analyses, and methodological framework papers published between 2009 and 2025. The studies evaluated secondary malignancy risk following radiotherapy across multiple anatomical sites, including breast, mediastinal lymphoma, thymoma, prostate, pelvic, craniospinal, and head-and-neck cancers. Methodological approaches included Monte Carlo–based dosimetric modeling, epidemiology-derived risk projection models, mechanistic biological models, and emerging machine-learning and radiomics-based frameworks (Paganetti, 2009; Joosten et al., 2014; Meyer et al., 2024).
| Author (Year) | Location | Paper Title | Procedure | Methodology (Including Modelling) | Key Findings | Conclusion | Identified Gaps |
| König et al. (2020) | Germany | Secondary malignancy risk following proton vs. X-ray treatment of mediastinal malignant lymphoma | Mediastinal RT (Proton vs Photon) | Treatment planning + organ-specific excess absolute risk (EAR) & excess relative risk (ERR) models | Proton therapy reduced predicted lung and breast secondary cancer risk by 40–60% compared to photons | Proton therapy offers substantial long-term cancer risk reduction | Lack of long-term epidemiological validation (König et al., 2020) |
| Cella et al. (2024) | Italy | Modeling frameworks for radiation-induced lymphopenia | Multi-site RT | Review of mechanistic, NTCP, and ML models | Dose-to-blood and lymphoid organs strongly predicts lymphopenia | Lymphopenia modeling is central to late cancer risk and survival | Limited integration with secondary cancer endpoints (Cella et al., 2024) |
| Paganetti et al. (2020) | USA | Secondary cancer risk after breast RT: Photon vs Proton | Breast RT | Monte Carlo dose + organ-specific cancer risk models | Proton plans showed lower contralateral breast and lung risk | Proton RT reduces lifetime secondary cancer risk | Age- and genetic-specific risks not fully addressed (Paganetti et al., 2020) |
| Mazonakis et al. (2024) | Greece | Second cancer and cardiotoxicity risk after thymoma irradiation | Thymoma RT | Treatment planning + BEIR VII risk models | Elevated lung, breast, and cardiac risk with higher mean doses | Dose optimization critical in mediastinal RT | No patient follow-up data (Mazonakis et al., 2024) |
| Timlin et al. (2015) | UK | 3D calculation of radiation-induced second cancer risk | Multi-site RT | Voxel-based dose-response modeling accounting for tissue heterogeneity | Risk varied significantly within organs | 3D modeling improves individual risk estimation | High computational demand (Timlin et al., 2015) |
| Stokkevåg et al. (2015) | Norway | Secondary rectal and bladder cancer risk after prostate RT | Prostate RT | Epidemiology-informed dose–response modeling | Increased rectal and bladder cancer risk with pelvic dose | Long-term vigilance required | Limited proton therapy comparison (Stokkevåg et al., 2015) |
| Shcherbakov et al. (2025) | Russia | Physical factors in development of secondary cancers | Various RT | Physical dose, LET, scatter analysis | Secondary cancer risk linked to neutron contamination and scatter | Physical parameters significantly influence carcinogenesis | No biological modeling integration (Shcherbakov et al., 2025) |
| Paganetti (2009) | USA | Computational patient models for radiation-induced cancers | General RT | Monte Carlo computational phantoms | Patient-specific anatomy strongly affects risk estimates | Computational models are essential for risk prediction | Limited clinical translation (Paganetti, 2009) |
| Tohidinezhad et al. (2022) | Netherlands | Cardiac toxicity prediction models after lung RT | Lung RT | Systematic review + meta-analysis of NTCP & ML models | Mean heart dose predictive of late toxicity | Cardiac models complement secondary cancer risk | Secondary malignancies not primary endpoint (Tohidinezhad et al., 2022) |
| Zhang et al. (2020) | China | Secondary cancer risk after breast RT techniques | Breast RT | Monte Carlo + BEIR VII | IMRT increased low-dose bath and second cancer risk | Technique selection impacts long-term risk | No proton comparison (Zhang et al., 2020) |
| Gandhi et al. (2025) | India | SIRI-RT nomogram for secondary malignancy prediction | Mixed RT | Biomarker-driven nomogram | Inflammatory markers predicted secondary malignancy | Biological indices enhance prediction | External validation lacking (Gandhi et al., 2025) |
| Mazonakis et al. (2017) | Greece | Second cancer risk after Hodgkin lymphoma RT | Mediastinal RT | Monte Carlo + organ-specific risk coefficients | Modern ISRT reduces predicted second cancers | Field reduction is beneficial | Pediatric risk not addressed (Mazonakis et al., 2017) |
| Gomes et al. (2025) | Europe | Cardiac dysfunction prediction after cancer therapy | Multi-site RT | Meta-analysis of predictive models | Identified robust predictors of late cardiac effects | Supports personalized survivorship modeling | Cancer-specific integration needed (Gomes et al., 2025) |
| Carbonara et al. (2021) | Italy | Radiomics & ML for RT toxicity prediction | Head & neck RT | Radiomics + ML systematic review | Imaging features predicted toxicity risk | AI improves personalization | Secondary cancer risk not directly modeled (Carbonara et al., 2021) |
| Nuijens et al. (2025) | Netherlands | Personalized RT risk factors in pelvic cancer | Pelvic RT | Clinical & biological factor analysis | Age, comorbidities influence late toxicity | Patient factors crucial for personalization | Cancer induction modeling absent (Nuijens et al., 2025) |
| König et al. (2022) | Germany | Proton vs photon risk in thymic tumors | Thymic RT | Organ-specific risk modeling | Proton RT reduced lung and breast risk | Proton advantage reaffirmed | Long-term cohort data missing (König et al., 2022) |
| Paganetti (2012) | USA | Second malignancy from scattered radiation | General RT | Scatter and neutron dose modeling | Secondary radiation contributes to cancer risk | Out-of-field dose must be minimized | Limited clinical correlation (Paganetti, 2012) |
| De Kermenguy et al. (2025) | France | Radiation-induced lymphopenia modeling | Multi-site RT | Mathematical + mechanistic learning models | Improved lymphocyte depletion prediction | Mechanistic AI bridges biology and dosimetry | Link to carcinogenesis indirect (De Kermenguy et al., 2025) |
| Joosten et al. (2014) | Switzerland | Evaluation of secondary cancer risk models | Breast RT | Monte Carlo + comparative risk models | Large variability between models | Model selection critically affects risk | No gold-standard model (Joosten et al., 2014) |
| Kachris & Mazonakis (2024) | Greece | Rectal cancer RT and induced malignancies | Rectal RT | Epidemiological + dosimetric synthesis | Increased pelvic second cancer risk | Long-term risk significant | Genetic susceptibility ignored (Kachris & Mazonakis, 2024) |
| Bednarz & Besemer (2017) | USA | Second cancer risk from radionuclide therapy | Radionuclide therapy | Organ dose-based risk modeling | Elevated leukemia and solid cancer risk | Risk assessment needed beyond EBRT | Limited patient-specific dosimetry (Bednarz & Besemer, 2017) |
| Haciislamoglu et al. (2020) | Turkey | Secondary cancer risk after prostate RT | Prostate RT | Monte Carlo + BEIR VII | IMRT increased low-dose exposure | Technique optimization essential | No proton arm (Haciislamoglu et al., 2020) |
| Baghani & Porouhan (2024) | Iran | Secondary cancer risk after craniospinal irradiation | CSI | Monte Carlo organ dosimetry | High risk in thyroid and lungs | CSI requires stringent optimization | Pediatric-specific modeling limited (Baghani & Porouhan, 2024) |
| Meyer et al. (2024) | USA | TOPAS-based patient-specific risk framework | Multi-site RT | Monte Carlo TOPAS + in/out-of-field modeling | Accurate individualized risk estimates | Enables clinical implementation | Computational intensity (Meyer et al., 2024) |
| Takata et al. (2020) | Japan | Monte Carlo estimation of second cancer risk | Breast RT | Internal body scatter Monte Carlo | Significant out-of-field dose contribution | Scatter modeling essential | Limited biological weighting (Takata et al., 2020) |
| Kang et al. (2021) | South Korea | Clinical RT-induced cancer risk calculator | VMAT | Monte Carlo engine + software tool | Automated patient-specific risk estimation | Facilitates clinical adoption | Validation cohort small (Kang et al., 2021) |
| Li et al. (2025) | USA | Patient-specific lymphopenia modeling in H&N RT | Head & neck RT | Dose-to-immune-structure modeling | Accurate lymphopenia prediction | Immune modeling relevant to cancer risk | Secondary malignancy link indirect (Li et al., 2025) |
| Mirjolet et al. (2022) | France | Breast radio-induced sarcoma risk factors | Breast RT | Retrospective epidemiological analysis | Dose and field size correlated with sarcoma | Treatment factors influence rare cancers | Molecular susceptibility unknown (Mirjolet et al., 2022) |
| D’Anna et al. (2025) | Italy | Lung cancer risk after breast RT fractionation | Breast RT | Retrospective dosimetric comparison | Hypofractionation reduced lung dose | Fractionation impacts second cancer risk | Limited follow-up duration (D’Anna et al., 2025) |
Table 1: An overview of the results.
Dosimetric Modeling Outcomes
As shown in Table 1, absorbed organ dose and the spatial distribution of low-dose exposure were consistently identified as dominant predictors of secondary cancer risk. Monte Carlo–based dose reconstructions demonstrated pronounced intra-organ dose heterogeneity, which is inadequately captured by conventional mean-dose metrics (Timlin et al., 2015; Joosten et al., 2014). Several treatment-planning studies reported that highly conformal photon techniques, particularly IMRT and VMAT, were associated with increased low-dose exposure to surrounding normal tissues, resulting in higher projected lifetime attributable risk for organs such as the lung, breast, bladder, and rectum (Zhang et al., 2020; Haciislamoglu et al., 2020).
Comparison of Radiotherapy Techniques
Multiple studies summarized in Table 1 compared photon-based and proton-based radiotherapy techniques. Across disease sites, including mediastinal lymphoma, thymic epithelial tumors, and breast cancer, proton therapy was associated with a predicted reduction of approximately 40–60% in organ-specific excess absolute risk compared with photon therapy (König et al., 2020; Paganetti et al., 2020; König et al., 2022). These reductions were primarily attributed to lower integral dose and reduced out-of-field radiation exposure.
Epidemiological Risk Estimates
Several investigations translated absorbed dose distributions into lifetime cancer risk estimates using epidemiological risk coefficients derived from atomic-bomb survivor cohorts and medically exposed populations, such as BEIR VII-based models (Stokkevåg et al., 2015; Takata et al., 2020). As reported in Table 1, substantial variability in predicted risk estimates was observed depending on the selected dose–response model, highlighting inter-model uncertainty (Joosten et al., 2014).
Biological and Data-Driven Modeling Results
Beyond physical dose metrics, studies in Table 1 evaluated biological and data-driven predictors of radiation-induced toxicity and secondary cancer risk. Modeling of radiation-induced lymphopenia demonstrated strong associations between dose to circulating blood and lymphoid organs and persistent immune suppression (Cella et al., 2024; De Kermenguy et al., 2025). Machine-learning, radiomics, and biomarker-based models improved individual-level risk stratification compared with conventional dosimetric approaches, although most studies reported limited external validation (Carbonara et al., 2021; Gandhi et al., 2025).
Discussion of the Overview Results
The findings summarized in Table 1 indicate that radiation-induced secondary malignancy risk is driven by a combination of physical, biological, and treatment-related factors. Dose distribution characteristics, particularly low-dose exposure to surrounding normal tissues, were consistently identified as critical determinants of long-term cancer risk. The observed superiority of proton therapy in reducing modeled secondary cancer risk across multiple disease sites supports its potential role in risk-adaptive radiotherapy, especially for younger patients and long-term survivors (König et al., 2020; Paganetti et al., 2020).
Methodological Implications: Role of Biological and Immunological Factors
The substantial variability observed across epidemiological risk models underscores the limitations of applying population-averaged coefficients to individualized radiotherapy dose distributions. As demonstrated in Table 1, differences in model selection can result in clinically meaningful divergence in predicted lifetime cancer risk (Joosten et al., 2014). These findings highlight the need for harmonized, clinically validated risk models that better reflect contemporary radiotherapy practices. The inclusion of radiation-induced lymphopenia and immune-related modeling in several studies reflects an emerging recognition of biological modifiers of late radiation effects. Although secondary cancer incidence was not directly quantified in these models, immune suppression may influence carcinogenesis and tumor surveillance, suggesting an indirect pathway linking radiotherapy exposure to late malignant outcomes (Cella et al., 2024; Li et al., 2025). Future risk models may benefit from integrating biological response parameters alongside dosimetric data.
Emerging Data-Driven Approaches and Limitations of the Evidence Base
Machine-learning and radiomics-based models summarized in Table 1 demonstrate potential for improving patient-specific risk prediction. However, limited sample sizes, lack of external validation, and reduced interpretability remain significant barriers to clinical implementation. These challenges highlight the importance of transparent model development and prospective validation before adoption in routine practice (Carbonara et al., 2021; Gandhi et al., 2025). This review identified several limitations within the existing literature. Most studies rely on modeling rather than long-term clinical outcome data, genetic susceptibility and lifestyle factors are rarely incorporated, and representation from low- and middle-income countries is limited. Furthermore, few frameworks integrate dosimetric, biological, and clinical predictors within a unified modeling architecture (Paganetti, 2012; Meyer et al., 2024). Future studies should prioritize longitudinal cohort validation of secondary cancer risk models, development of region-specific risk coefficients, and integration of biological and clinical modifiers into unified predictive frameworks. Such efforts are essential to translate patient-specific secondary malignancy risk modeling into routine radiotherapy planning and survivorship care.
Regional and Thematic Pattern of the results
The regional distribution of included studies, as summarized in Table 2, shows a predominant contribution from Europe and North America, accounting for over 70% of the literature (König et al., 2020; Paganetti et al., 2020; Timlin et al., 2015). Key countries include Germany, Italy, Switzerland, Greece, France, the UK, and the United States. Studies from Asia—notably China, Japan, South Korea, and Iran contributed focused investigations into breast, craniospinal, and VMAT-related secondary cancer risks (Zhang et al., 2020; Takata et al., 2020; Kang et al., 2021; Baghani & Porouhan, 2024). Notably, there was no representation from Africa or South America, highlighting a significant geographical evidence gap. This regional bias indicates that current secondary cancer risk models may primarily reflect demographics and treatment practices in high-resource settings, limiting their applicability in populations with differing genetic, epidemiologic, or radiotherapy infrastructure characteristics. Therefore, there is a critical need to expand research to low- and middle-income countries to develop globally generalizable, patient-specific risk models.
| Theme | Number of Studies (%) | References | Key Findings | Dominant Regions |
| Dosimetric & Physics-Based Modeling | 14 (35%) | Timlin et al., 2015; Joosten et al., 2014; Stokkevåg et al., 2015; Shcherbakov et al., 2025; Paganetti, 2009; Takata et al., 2020; Kang et al., 2021; Bednarz & Besemer, 2017; Zhang et al., 2020; Haciislamoglu et al., 2020; Mazonakis et al., 2017; Mazonakis et al., 2024; König et al., 2020; König et al., 2022 | Monte Carlo–based organ dose modeling showed organ-specific absorbed dose and low-dose bath as strongest predictors; heterogeneity in dose-response highlighted importance of tissue-specific modeling; IMRT/VMAT increased low-dose exposure to surrounding organs | Europe, North America, Asia |
| Radiotherapy Modality Comparison (Photon vs Proton) | 8 (20%) | König et al., 2020; Paganetti et al., 2020; König et al., 2022; Paganetti, 2012; Zhang et al., 2020; Mazonakis et al., 2024; Mirjolet et al., 2022; D’Anna et al., 2025 | Proton therapy reduced modeled secondary cancer risk by 40–60%; lower integral dose and reduced out-of-field exposure; consistency across disease sites (mediastinal lymphoma, thymic tumors, breast cancer) | Europe, North America, Asia |
| Epidemiological Risk Projection | 6 (15%) | Stokkevåg et al., 2015; Takata et al., 2020; Joosten et al., 2014; Kachris & Mazonakis, 2024; Baghani & Porouhan, 2024; Bednarz & Besemer, 2017 | Lifetime risk estimates derived using BEIR VII and other population-based risk coefficients; substantial variability depending on model choice; moderate reliability for patient-specific predictions | Europe, Asia |
| Biological & Immunological Modeling | 5 (12.5%) | Cella et al., 2024; De Kermenguy et al., 2025; Li et al., 2025; Nuijens et al., 2025; Gandhi et al., 2025 | Radiation-induced lymphopenia models linked dose to circulating blood/lymphoid organs with persistent immune suppression; indirect effect on carcinogenesis; mechanistic insights provided | Europe, North America |
| Machine Learning & Data-Driven Models | 7 (17.5%) | Carbonara et al., 2021; Gandhi et al., 2025; Anbumani et al., 2024; Kuipers et al., 2024; Gomes et al., 2025; Zhang et al., 2020; Mazonakis et al., 2024 | ML, radiomics, and biomarker-based models improved individual-level risk prediction; limited external validation and interpretability; data-driven frameworks showed potential for personalized risk estimation | Europe, Asia |
Table 2: Quantitative thematic dominance and Regional Distribution of Results.
Thematic Pattern
The included studies were systematically categorized into five major thematic domains, as summarized in Table 2, to reflect both methodological orientation and clinical relevance: dosimetric and physics-based modeling, radiotherapy modality comparisons (photon versus proton techniques), epidemiological risk projection, biological and immunological modeling, and machine learning–driven, data-centric approaches. This thematic stratification provides a structured framework for synthesizing heterogeneous evidence, facilitates comparison across modeling paradigms, and supports PRISMA-compliant interpretation of how different analytical perspectives contribute to secondary cancer risk assessment in radiotherapy (Moher et al., 2009; Page et al., 2021).
Dosimetric and physics-based modeling
The dosimetric and physics-based modeling domain comprised 14 studies (35%), representing the largest proportion of the included literature (Table 2), with Monte Carlo–based dosimetric simulations emerging as the dominant methodological approach. These models were applied across a wide range of anatomical sites, including mediastinal lymphoma, breast, prostate, pelvic, and craniospinal radiotherapy, reflecting their versatility in estimating both in-field and out-of-field organ doses (Timlin et al., 2015; Joosten et al., 2014; Stokkevåg et al., 2015; Shcherbakov et al., 2025; Paganetti, 2009). Across studies, organ-specific absorbed dose and the extent of the low-dose bath were consistently identified as the strongest predictors of radiation-induced secondary malignancy risk. Although highly conformal photon techniques such as intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) improved target dose conformity and tumor coverage, they were also associated with increased low-dose exposure to surrounding normal tissues, potentially elevating long-term secondary cancer risk (Zhang et al., 2020; Haciislamoglu et al., 2020). Furthermore, substantial heterogeneity in tissue response was observed, underscoring the limitations of population-averaged risk coefficients and reinforcing the need for organ- and patient-specific dosimetric modeling. Collectively, these findings demonstrate that while dosimetric precision is fundamental to secondary cancer risk assessment, even advanced radiotherapy techniques require careful optimization of low-dose spread to balance therapeutic efficacy with long-term radiological safety.
Radiotherapy Modality Comparisons (Photon vs Proton)
Comparative analyses of radiotherapy modalities constituted eight studies (20%) of the included literature, focusing on modeling-based evaluations of proton versus photon therapy across multiple disease sites, including mediastinal lymphoma, thymic epithelial tumors, and breast cancer (König et al., 2020; Paganetti et al., 2020; König et al., 2022; Paganetti, 2012). Collectively, these studies consistently reported a substantial reduction in predicted secondary cancer risk with proton therapy, typically in the range of 40–60%, attributable primarily to the lower integral dose and markedly reduced out-of-field radiation exposure inherent to proton beam characteristics. This dosimetric advantage was particularly pronounced in younger patient populations with long life expectancy, highlighting the relevance of proton therapy within risk-adaptive and personalized radiotherapy frameworks. The observed consistency of findings across European and North American cohorts supports methodological reproducibility and robustness of the modeling approaches; however, all conclusions were derived from computational risk estimates, with limited corroboration from long-term clinical or epidemiological outcome data. Overall, this thematic evidence underscores the modality-dependent nature of radiation-induced secondary cancer risk and reinforces the potential role of proton therapy as a strategic option for secondary cancer risk mitigation in appropriately selected patients.
Epidemiological Risk Projection
Six studies (15%) employed population-based epidemiological modeling approaches, primarily using BEIR VII risk coefficients to estimate radiation-induced secondary cancer risk across diverse treatment sites and patient populations (Stokkevåg et al., 2015; Joosten et al., 2014; Takata et al., 2020; Kachris & Mazonakis, 2024; Baghani & Porouhan, 2024). These models enabled standardized lifetime risk estimates and facilitated comparisons across multiple patient groups; however, predicted risks varied substantially depending on the selected dose–response assumptions, highlighting inherent uncertainty in individual-level risk prediction. While epidemiological models provide broad applicability and methodological consistency, their reliance on population-averaged coefficients limits precision for patient-specific assessments, making them moderately reliable for individualized clinical decision-making. Optimal use of these models involves integration with detailed dosimetric data and patient-specific biological information. Collectively, this thematic domain underscores the trade-off between standardization and personalization in secondary cancer risk modeling, emphasizing the need for combined epidemiological, dosimetric, and biological approaches in contemporary radiotherapy risk assessment.
Biological and Immunological Modeling
Five studies (12.5%) focused on radiation-induced lymphopenia and immune-mediated mechanisms (Cella et al., 2024; De Kermenguy et al., 2025; Li et al., 2025; Nuijens et al., 2025; Gandhi et al., 2025). The findings as indicated from table 2, Dose to circulating blood and lymphoid organs strongly influenced persistent immune suppression. These models provide mechanistic insight into secondary malignancy risk, although they do not directly quantify cancer incidence. Incorporating biological parameters could enhance patient-specific predictive accuracy, particularly when combined with dosimetric data. This thematic domain underscores the importance of multi-dimensional modeling, combining physical, biological, and clinical predictors.
Machine Learning and Data-Driven Models
Seven studies (17.5%) investigated machine learning, radiomics, and biomarker-driven risk models, representing a rapidly emerging approach to personalized secondary cancer risk estimation (Carbonara et al., 2021; Gandhi et al., 2025; Anbumani et al., 2024; Kuipers et al., 2024; Gomes et al., 2025; Zhang et al., 2020; Mazonakis et al., 2024). These studies demonstrated that machine learning models can enhance patient-level risk stratification by integrating imaging features, serum biomarkers, and predictive nomograms, providing more individualized assessments than traditional approaches. Nonetheless, external validation of these models remains limited, and challenges related to interpretability may impede immediate clinical application. Despite these limitations, combining machine learning frameworks with conventional dosimetric and biological models holds substantial promise for improving precision in radiotherapy decision-making and optimizing patient-specific risk management.
General Trends in Secondary Malignancy Risk Modelling
Based on Table 2, dosimetric and physics-based modelling approaches predominate in the assessment of secondary malignancy risk, reflecting their strong theoretical foundation, reproducibility, and direct linkage between absorbed dose distributions and organ-specific cancer induction, which together make them the most extensively applied frameworks in radiotherapy research (Schneider et al., 2011; Hall & Giaccia, 2019). Across the reviewed studies, proton therapy consistently demonstrates a reduced predicted risk of secondary cancers compared with conventional photon-based modalities, attributable to superior dose conformality and reduced integral and exit doses, underscoring clear modality-specific radioprotection benefits (Newhauser & Durante, 2011; Paganetti, 2014). Epidemiological risk models, largely derived from large cohort and atomic-bomb survivor data, provide standardized population-level risk estimates; however, their applicability to individual patients remains limited by the use of averaged risk coefficients and the inability to fully account for patient-specific biological and treatment-related variability (BEIR VII, 2006; UNSCEAR, 2020). In contrast, biological and radiobiological modeling approaches contribute important mechanistic insights by incorporating DNA damage response, bystander effects, and immune-mediated modulation of carcinogenesis, thereby extending risk assessment beyond purely dosimetric considerations (Durante et al., 2013; Little et al., 2014). Emerging machine-learning–based models offer substantial potential for individualized secondary cancer risk prediction through the integration of dosimetric, clinical, and biological variables; nevertheless, their routine clinical adoption is constrained by limited datasets, heterogeneity, lack of external validation, and challenges related to model interpretability (Lambin et al., 2017; König et al., 2022)
Evidence Gaps, Regional Limitations and Future Directions
The review highlights significant evidence gaps and regional limitations, with the majority of included studies concentrated in high-income regions possessing advanced radiotherapy infrastructure, while Africa, South America, and other underrepresented regions remain largely unstudied. This geographic bias limits the generalizability of current secondary cancer risk models and underscores the need to integrate region-specific patient data to develop globally applicable assessments. Future research should prioritize longitudinal validation of predicted secondary cancer risk models through extended clinical follow-up and linkage with population-based cancer registries, as many current estimates rely on extrapolated risk coefficients rather than observed outcomes (Berrington de González et al., 2013). Furthermore, incorporating physical dosimetry, radiobiological susceptibility markers, and advanced machine-learning predictors is critical to capturing inter-patient variability and complex, non-linear risk interactions (Giordano et al., 2019; König et al., 2022). Expanding investigations to low- and middle-income countries is essential to ensure that predictive models reflect diverse treatment technologies, demographic characteristics, and clinical practices. Finally, translational efforts should focus on embedding validated multi-domain predictive models into routine radiotherapy planning systems, facilitating patient-specific risk–benefit optimization and supporting personalized radiotherapy in accordance with contemporary radiological protection principles (ICRP, 2021).
This systematic review demonstrates that secondary malignancy risk following radiotherapy is not solely a function of delivered dose but arises from the interplay of physical dose characteristics, treatment technique, and patient-specific biological factors. Monte Carlo–based dosimetric modeling remains the most robust and widely applied approach, consistently identifying low-dose exposure to surrounding normal tissues as a critical determinant of long-term carcinogenic risk. Comparative modeling studies strongly suggest that proton therapy confers a substantial reduction in predicted secondary cancer risk relative to photon-based techniques, particularly in younger patients and those with long expected survival. However, reliance on population-averaged epidemiological risk coefficients introduces significant uncertainty in individualized risk prediction. Emerging biological and immunological models, particularly those addressing radiation-induced lymphopenia, offer valuable mechanistic insight but are rarely integrated directly into secondary cancer risk frameworks. Machine-learning and radiomics-based approaches show promise for personalized risk estimation but remain constrained by limited datasets, lack of interpretability, and insufficient external validation. Overall, the current evidence base is heavily concentrated in high-income regions, limiting the generalizability of findings to low- and middle-income countries. Bridging these gaps requires harmonized modeling frameworks, longitudinal validation using real-world clinical outcomes, and broader geographic representation. Advancing patient-specific secondary malignancy risk assessment is essential for optimizing the therapeutic ratio of radiotherapy and supporting informed, risk-adaptive clinical decision-making.
Integration of multi-domain modeling and clinical validation: Future advances in secondary malignancy risk assessment should focus on the development of unified, multi-domain modeling frameworks that integrate dosimetric, biological, and clinical variables within a single predictive architecture. Radiation-induced carcinogenesis is inherently multifactorial, involving complex interactions between organ-specific dose distributions, radiation quality, patient age, genetic susceptibility, immune competence, and treatment-related factors. Isolated modeling approaches—whether purely dosimetric, epidemiological, or biological—are insufficient to capture this complexity. Integrative frameworks that combine Monte Carlo–derived organ doses, biological modifiers such as radiation-induced lymphopenia, and patient-specific clinical characteristics can provide more realistic and individualized risk estimates. However, for such models to achieve clinical credibility, longitudinal validation against real-world outcomes is essential. Modeled secondary cancer risks must be tested against long-term follow-up data and population-based cancer registries to reduce uncertainty arising from extrapolated risk coefficients and population-averaged assumptions. This validation process will strengthen confidence in predictive models and facilitate their translation into routine radiotherapy planning and survivorship care. Optimization of treatment planning and risk-adaptive modality selection: Routine incorporation of low-dose metrics into treatment planning systems represents a critical step toward risk-informed radiotherapy optimization. While modern techniques such as IMRT and VMAT offer superior target conformity, they often increase the low-dose bath and out-of-field exposure to surrounding normal tissues, which has been consistently associated with elevated secondary cancer risk. Explicit evaluation of volumetric low-dose parameters and peripheral organ doses should therefore complement conventional target-based plan evaluation criteria. In parallel, risk-adaptive selection of radiotherapy modality should be encouraged, particularly for younger patients and long-term survivors. Proton therapy, by virtue of its reduced integral dose and minimal exit radiation, has demonstrated substantial modeled reductions in secondary malignancy risk across multiple disease sites. Incorporating patient age, life expectancy, and long-term risk projections into modality selection frameworks can help balance immediate tumor control with future cancer risk, thereby supporting personalized and ethically informed treatment decisions. Global applicability, standardization, and responsible use of artificial intelligence: The generalizability of current secondary malignancy risk models is limited by the strong concentration of evidence from high-income regions. Expanding research efforts to low- and middle-income countries, including Africa, is essential to develop region-specific risk models that reflect local demographics, cancer patterns, and radiotherapy infrastructure. Such efforts will improve global equity in radiological protection and ensure that predictive frameworks are applicable across diverse clinical settings. Concurrently, the field would benefit from standardization and harmonization of modeling approaches, including consensus guidelines on model selection, reporting standards, uncertainty quantification, and minimum validation requirements. These measures would enhance comparability across studies and accelerate clinical adoption. Finally, while machine learning and artificial intelligence offer powerful tools for personalized risk prediction, their clinical deployment must be approached responsibly. Rigorous external validation, transparent model design, and interpretability should be prioritized over purely predictive accuracy to ensure trust, reproducibility, and safe integration of AI-driven tools into radiotherapy decision-making.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
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Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
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The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain.
Dear Ms. Mayra Duenas, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. “The International Journal of Clinical Case Reports and Reviews represented the “ideal house” to share with the research community a first experience with the use of the Simeox device for speech rehabilitation. High scientific reputation and attractive website communication were first determinants for the selection of this Journal, and the following submission process exceeded expectations: fast but highly professional peer review, great support by the editorial office, elegant graphic layout. Exactly what a dynamic research team - also composed by allied professionals - needs!" From, Chiara Beccaluva, PT - Italy.
Dear Maria Emerson, Editorial Coordinator, we have deeply appreciated the professionalism demonstrated by the International Journal of Clinical Case Reports and Reviews. The reviewers have extensive knowledge of our field and have been very efficient and fast in supporting the process. I am really looking forward to further collaboration. Thanks. Best regards, Dr. Claudio Ligresti
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation. “The peer review process was efficient and constructive, and the editorial office provided excellent communication and support throughout. The journal ensures scientific rigor and high editorial standards, while also offering a smooth and timely publication process. We sincerely appreciate the work of the editorial team in facilitating the dissemination of innovative approaches such as the Bonori Method.” Best regards, Dr. Matteo Bonori.
I recommend without hesitation submitting relevant papers on medical decision making to the International Journal of Clinical Case Reports and Reviews. I am very grateful to the editorial staff. Maria Emerson was a pleasure to communicate with. The time from submission to publication was an extremely short 3 weeks. The editorial staff submitted the paper to three reviewers. Two of the reviewers commented positively on the value of publishing the paper. The editorial staff quickly recognized the third reviewer’s comments as an unjust attempt to reject the paper. I revised the paper as recommended by the first two reviewers.
Dear Maria Emerson, Editorial Coordinator, Journal of Clinical Research and Reports. Thank you for publishing our case report: "Clinical Case of Effective Fetal Stem Cells Treatment in a Patient with Autism Spectrum Disorder" within the "Journal of Clinical Research and Reports" being submitted by the team of EmCell doctors from Kyiv, Ukraine. We much appreciate a professional and transparent peer-review process from Auctores. All research Doctors are so grateful to your Editorial Office and Auctores Publishing support! I amiably wish our article publication maintained a top quality of your International Scientific Journal. My best wishes for a prosperity of the Journal of Clinical Research and Reports. Hope our scientific relationship and cooperation will remain long lasting. Thank you very much indeed. Kind regards, Dr. Andriy Sinelnyk Cell Therapy Center EmCell
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. It was truly a rewarding experience to work with the journal “Clinical Cardiology and Cardiovascular Interventions”. The peer review process was insightful and encouraging, helping us refine our work to a higher standard. The editorial office offered exceptional support with prompt and thoughtful communication. I highly value the journal’s role in promoting scientific advancement and am honored to be part of it. Best regards, Meng-Jou Lee, MD, Department of Anesthesiology, National Taiwan University Hospital.
Dear Editorial Team, Journal-Clinical Cardiology and Cardiovascular Interventions, “Publishing my article with Clinical Cardiology and Cardiovascular Interventions has been a highly positive experience. The peer-review process was rigorous yet supportive, offering valuable feedback that strengthened my work. The editorial team demonstrated exceptional professionalism, prompt communication, and a genuine commitment to maintaining the highest scientific standards. I am very pleased with the publication quality and proud to be associated with such a reputable journal.” Warm regards, Dr. Mahmoud Kamal Moustafa Ahmed
Dear Maria Emerson, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews’, I appreciate the opportunity to publish my article with your journal. The editorial office provided clear communication during the submission and review process, and I found the overall experience professional and constructive. Best regards, Elena Salvatore.
Dear Mayra Duenas, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews Herewith I confirm an optimal peer review process and a great support of the editorial office of the present journal
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. I am really grateful for the peers review; their feedback gave me the opportunity to reflect on the message and impact of my work and to ameliorate the article. The editors did a great job in addition by encouraging me to continue with the process of publishing.
Dear Cecilia Lilly, Editorial Coordinator, Endocrinology and Disorders, Thank you so much for your quick response regarding reviewing and all process till publishing our manuscript entitled: Prevalence of Pre-Diabetes and its Associated Risk Factors Among Nile College Students, Sudan. Best regards, Dr Mamoun Magzoub.
International Journal of Clinical Case Reports and Reviews is a high quality journal that has a clear and concise submission process. The peer review process was comprehensive and constructive. Support from the editorial office was excellent, since the administrative staff were responsive. The journal provides a fast and timely publication timeline.
Dear Maria Emerson, Editorial Coordinator of International Journal of Clinical Case Reports and Reviews, What distinguishes International Journal of Clinical Case Report and Review is not only the scientific rigor of its publications, but the intellectual climate in which research is evaluated. The submission process is refreshingly free of unnecessary formal barriers and bureaucratic rituals that often complicate academic publishing without adding real value. The peer-review system is demanding yet constructive, guided by genuine scientific dialogue rather than hierarchical or authoritarian attitudes. Reviewers act as collaborators in improving the manuscript, not as gatekeepers imposing arbitrary standards. This journal offers a rare balance: high methodological standards combined with a respectful, transparent, and supportive editorial approach. In an era where publishing can feel more burdensome than research itself, this platform restores the original purpose of peer review — to refine ideas, not to obstruct them Prof. Perlat Kapisyzi, FCCP PULMONOLOGIST AND THORACIC IMAGING.
Dear Grace Pierce, International Journal of Clinical Case Reports and Reviews I appreciate the opportunity to review for Auctore Journal, as the overall editorial process was smooth, transparent and professionally managed. This journal maintains high scientific standards and ensures timely communications with authors, which is truly commendable. I would like to express my special thanks to editor Grace Pierce for his constant guidance, promt responses, and supportive coordination throughout the review process. I am also greatful to Eleanor Bailey from the finance department for her clear communication and efficient handling of all administrative matters. Overall, my experience with Auctore Journal has been highly positive and rewarding. Best regards, Sabita sinha
Dear Mayra Duenas, Editorial Coordinator of the journal IJCCR, I write here a little on my experience as an author submitting to the International Journal of Clinical Case Reports and Reviews (IJCCR). This was my first submission to IJCCR and my manuscript was inherently an outsider’s effort. It attempted to broadly identify and then make some sense of life’s under-appreciated mysteries. I initially had responded to a request for possible submissions. I then contacted IJCCR with a tentative topic for a manuscript. They quickly got back with an approval for the submission, but with a particular requirement that it be medically relevant. I then put together a manuscript and submitted it. After the usual back-and-forth over forms and formality, the manuscript was sent off for reviews. Within 2 weeks I got back 4 reviews which were both helpful and also surprising. Surprising in that the topic was somewhat foreign to medical literature. My subsequent updates in response to the reviewer comments went smoothly and in short order I had a series of proofs to evaluate. All in all, the whole publication process seemed outstanding. It was both helpful in terms of the paper’s content and also in terms of its efficient and friendly communications. Thank you all very much. Sincerely, Ted Christopher, Rochester, NY.
