Evaluating the Usefulness of the Prognostic Nutritional Index and Controlling Nutritional Status in Stratifying Prognosis in Cancer Patients during Gaza War, 2024

Evaluating the Usefulness of the Prognostic Nutritional Index and Controlling Nutritional Status in Stratifying Prognosis in Cancer Patients during Gaza War, 2024 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluating the Usefulness of the Prognostic Nutritional Index and Controlling Nutritional Status in Stratifying Prognosis in Cancer Patients during Gaza War, 2024 Hadeel S. S. Abuaziz, Samah Alshami This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7398900/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Objective To evaluate the usefulness of nutritional index and disease risk index in prognosis of cancer patients. Methodology: A cross-sectional study was conducted among 100 subjects diagnosed with cancer who attended the Outpatient Oncology Clinic of Augusta Victoria Hospital (AVH) at Al Ahli Arab Hospital (AAH) in the Gaza Strip, State of Palestine, from September 2024 to December 2024. Results 100 participants in the study had a mean age of 50.16 years (± 14.50); their mean weight loss during the war was 15.3 kg (± 5.4), and their BMI was 23.45 (± 4.9). 63% of the participants had at least one family member with cancer, and 42% of them were related to first-degree relatives. 81% of participants only eat once a day if there is a meal present or they may skip meals for a while. 68% of patients complain and require medical assessment by an oncologist. Male patients had a worse prognosis status than female patients. According to the PNI, which shows that 66% of patients have a good prognosis while 34% have a poor prognosis status due to extremely hard conditions. Based on PNI and CONUT scoring interpretations, there was a statistically significant correlation between the type of malignancy and the PNI score (P = 0.002), and there were clinically significant disparities related to location variable (P = 0.022). Conclusion Tools like PNI and CONUT offer valuable, low-cost methods for assessing prognosis and nutritional status, especially for solid tumors. PNI could be used as an independent prognostic indicator for cancer status, while more studies are needed to assess the prognostic role of CONUT. Nutritional index Cancer patient war area Prognosis assessment Introduction Cancer is a large group of diseases that could affect almost any organ or tissue of the body when abnormal cells grow uncontrollably, go beyond their usual boundaries to invade adjoining parts of the body, and/or spread to other organs. The latter process is called metastasizing and is a major cause of death from cancer. A neoplasm and malignant tumor are other common names for cancer and considered as the second leading cause of death in the globe ( 1 ). Nutritional status has been widely correlated with the initiation and prognosis of cancer ( 2 ). There is growing evidence that a patient's nutritional state may have an impact on their prognosis from cancer. Stratifying patients into distinct risk groups (score < 18.5 and ≥ 18.5) for each TNM category revealed significantly varied median overall survival rates ( 3 ); this approach was created to help physicians' stage various cancer types according to established standards. The tumor's size (T), its degree of lymph node dissemination (N), and the existence of metastases (M) are all included in the TNM Staging System ( 4 ). Individuals with cancer are frequently diagnosed with cancer-associated malnutrition, which has factors connected to the individuals' unique lifestyles, the cancerous tumor, and the course of treatment. Despite the fact that malnutrition is a global issue linked to higher rates of morbidity, death, and expense, there hasn't been agreement on diagnostic standards in clinical settings ( 3 ). The survival and duration of treatment for cancer patients are strongly correlated with their nutritional health; as a result, several prognostic models incorporate information on nutrition ( 5 ), and earlier research had developed predictive models for cancer patients using the Patient-Generated Subjective Global Assessment (PG-SGA) ( 6 ). A professional evaluation component (which includes weight change, diseases related to diet, metabolic demand, and physical examination) and a patient-reported component (which includes weight, food consumption, symptoms, and activities and function) are both included in the PG-SGA ( 3 ). The Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) Score have been recently used as useful screening tools to describe the prognosis of many diseases in patients, including cancer ( 7 ). Anti-cancer therapy's primary goal is to improve patients' overall survival (OS), hence factors that indicate prognosis are of clinical and scientific significance ( 3 ). As malnutrition is well known to be closely associated with poor survival in patients with cancer, evaluation of nutritional status using nutritional markers has attracted attention in the context of survival outcomes of cancer patients. ( 8 ) Malnutrition, a sub-acute or chronic state in cancer patients, may impair immune function and increase susceptibility to infection and complications of the treatment, thus leading to an increased mortality of cancer patients ( 7 ). Methodology Study Design & Study Population: A cross-sectional study was conducted among 100 subjects diagnosed with cancer who attended the Outpatient Oncology Clinic of Augusta Victoria Hospital (AVH) at Al Ahli Arab Hospital (AAH) in the Gaza Strip, State of Palestine, from September 2024 to December 2024. Sampling Methods and Processing: Questionnaire interview : A questionnaire administered to patients: general information, socioeconomic data, family history, medical history, and therapeutic plan data related to cancer patients will be collected. Sample collection Venous blood samples were collected. A 5 ml syringe was used to withdraw about 4 ml of venous blood from all study participants using the venipuncture technique under quality control and safety procedures. Two ml of the collected blood was placed into sterile ethylene diamine tetra-acetic acid (EDTA) tubes for hematology testing (CBC). Two milliliters were delivered into a plain tube for chemistry and special tests. Serum and plasma were obtained from both tubes after centrifugation at 3500 rpm for 5 minutes for use in kidney function tests, liver function tests, lipid profile, LDH, CK, and ALB preparation. Serum samples were stored at 2–8°C if analysis was performed within 24 hours after collection; otherwise, they were stored at -20°C until analysis. Quality assessment procedures of pre-analytical, analytical, and post-analytical phases were applied to ensure a suitable assurance method was followed to maintain testing accuracy. All levels of controls for CBC and chemical tests were used to establish high quality across all tests throughout the research period and procedures. Internal and external quality control measures were also applied to manage the data and results. Statistical Analysis: The data entry was conducted on an exact basis by the researcher. The data accuracy was checked, and there were no missing values while filling out the data. Data was coded as needed before proceeding with the statistical analysis and cleaned for any illogical or error values. The researcher then used SPSS version 26 statistical tools to analyze the data. Results The study sample involved 100 individuals whose mean age was 50.16 years (± 14.50); 71% of participants were female, 66% of whom were married, and 19% were single. With a mean weight loss during the war of 15.3 kg (± 5.4) and a mean BMI of 23.45 (± 4.9), the northern Gaza Strip accounts for 70% of the population. Over the period of the preceding four months, from 1st December 2024 to 31st March 2025, 9% of attending patients in the Outpatient Oncology Clinic of Augusta Victoria Hospital at Al Ahli Arab Hospital lost their lives regarding their specific kind of cancer as a result of overall malnutrition conditions in the Gaza Strip due to war circumstances. 55% of them have been diagnosed as having breast cancer, 16% have colon cancer, 15% have thyroid cancer, 7% have prostate cancer, and 7% have another solid malignancy. Everyone whose participating carried out the established questionnaire and underwent specific laboratory testing. Based on the details obtained through the questionnaire, 63% of respondents had at least one family member diagnosed with cancer; around 52.38% of them have the same type of cancer, whereas 47.61% have a different type. However, 42% are related to first-degree relatives. 10% of patients stop taking their medications due to doctor consultation, and 68% stop for more than a year, according to war conditions. Both patients require additional follow-up and an oncology professional to handle their status, but during specific periods during the war, they were unable and struggling to communicate with their doctor until an international organization was able to provide some types of medications but not cover all the types of malignancies, even if they were administered intravenously (IV) or as tablets. 10% of them continue to take their medications and require ongoing monitoring during the course of therapy and management, whereas 12% of them take their medication and then stop for follow-up under medical observation. Of these patients, 25% just received surgical treatment, 48% had non-surgical treatment, including 26% who were chemotherapy-dependent, and 27% received both surgical and nonsurgical treatment. According to their nutritional behaviors or dietary intake within this period of time, 81% of them only eat once a day if there is a meal available; even then, they might skip meals for a certain amount of time. After this, all civilians began receiving emergency assistance from international humanitarian organizations. This led to a modification in the patients' food intake and quality; 15% of the participants eat almost twice or three times a day, 68% of patients arrived at the clinic with complaints that required further investigation and an oncologist consultation, 17% of patients had hypertension (HTN), 6% had diabetes mellitus (DM), and 6% had both conditions. The prognostic nutritional index (PNI) indicates that 66% of patients have a good prognosis status because of the nature of the malignancy, which offers a favorable prognosis condition; 34% of patients have a poor prognosis. Male patients had a worse prognosis status than female patients, which was statistically significant (P value = 0.017). Additionally, there was a statistically significant correlation between the type of malignancy and the PNI score (P = 0.002). However, based on CONUT scoring and associated index interpretation, 89% of patients show normal nutritional status following an initial intake of better fortified food and supplements presented as emergency and humanitarian aid supplies, but 4% are still at mild nutritional risk and 7% are at moderate nutritional risk. Clinically significant differences were shown among patients in the north and south (P = 0.022), as well as among patients who are still alive and those who have passed away (P = 0.001) and those who have different types of cancer (P = 0.006). The non-surgical therapy options revealed a statistically significant picture for relations with the COUNT index (P = 0.02), in addition to their latest therapy dose (P = 0.001), whatever the cause of medication termination. A statistically significant difference was observed based on the last therapy dose variable (F (2.97) = 6.5, p = 0.002), the type of cancer (same or different) (F (2.97) = 3.4, p = 0.037), family history (F (2.97) = 3.76, p = 0.027), and geographic location (south or north) (F (2.97) = 3.98, p = 0.022) in a one-way ANOVA that examined the differences in nutritional risk groups according to a number of clinical and demographic variables. The normal nutritional risk group and the mild nutritional risk group differed significantly (p = 0.002) for the last therapeutic dose variable, based on Tukey's post hoc analysis. Statistically significant differences were observed between the mild and moderate nutritional risk groups (p = 0.046) and between the normal and mild nutritional risk groups (p = 0.022) with regards to the family history variable. The mild and moderate nutritional risk groups differed significantly (p = 0.032) in the particular type of cancer-associated variable (same or different with patient's disease). Finally, statistically significant differences between the moderate and mild nutritional risk groups (p = 0.033) and between the moderate and normal nutritional risk groups (p = 0.040) were observed for the location-based variable. Discussion The exceptional and challenging circumstances resulting from the ongoing war in Gaza have posed significant barriers to the healthcare system, particularly affecting vulnerable groups such as patients with noncommunicable diseases (NCDs), children, the elderly, and others with cancer. These unique conditions hinder the ability to compare our findings and those reported in another research. In this paper, we aimed to assess the prognostic value of the PNI and CONUT indices within a severely resource-limited environment. Although the study’s constraints, such as a limited data collection period and a relatively small sample size, may affect the final results, these limitations are inherent to the ongoing humanitarian crisis and require further research to clarify. Due to movement restrictions and safety concerns, patient access and data collection were considerably restricted. Nevertheless, the available data were utilized to conduct this analysis. To the best of the authors’ knowledge, there is currently no comparable study in the literature that has evaluated these prognostic markers under similar conditions. Unexplained weight loss is a well-known indicator of cancer progression and is commonly recognized as a marker of malnutrition status. In the context of our study, which was conducted during the war circumstances, the average weight loss observed was 15.3 ± 5.4 kg, highlighting the severity of nutritional deterioration under such circumstances. While treatment-related side effects, particularly those associated with chemotherapy, such as nausea, mucositis, vomiting, and altered taste change, are known contributors to malnutrition in cancer patients, this factor was less significant in our cohort. The majority of patients had temporarily discontinued their cancer treatment due to the war, limiting the direct impact of treatment-related nutritional decline in our sample. Malnutrition in our study was primarily associated with reduced food intake and altered energy expenditure, compounded by the challenges of displacement, inadequate shelter, and poor hygiene conditions. These findings are consistent with previous research indicating that elderly cancer patients are particularly vulnerable to malnutrition due to physiological, behavioral, economic, and environmental factors ( 9 , 10 ). Additionally, both our data and prior studies suggest a higher prevalence of malnutrition among male cancer patients compared to females. This may be partially explained by sociocultural factors specific to Arabic culture, where women often remain at home and receive greater familial support, potentially improving their nutritional intake and stability ( 9 , 12 ). Given these findings, it is imperative to implement routine nutritional assessments for all cancer patients throughout the treatment process. Early identification and management of malnutrition, in collaboration with oncologist consultation, are essential for improving outcomes and quality of life in this vulnerable population ( 10 ). PNI has emerged as a reliable independent prognostic indicator across various cancer types. Elevated PNI levels have been consistently associated with improved clinical outcomes, including in subgroups stratified of solid tumors ( 11 , 13 , 14 ). Specifically, a CONUT score > 3 or PNI ≤ 47.7 was indicative of an unfavorable prognosis ( 12 ), although in other studies, the CONUT score failed to retain predictive value ( 16 ). In elderly cancer patients, PNI has demonstrated a significant correlation with overall survival, suggesting its potential as a valuable, inexpensive prognostic tool. Given the increasing rate of cancer in aging populations, such accessible and practical biomarkers are essential to guide treatment strategies and optimize healthcare ( 13 ). Furthermore, high PNI values have been associated with improvement of responses to anti-cancer therapies and have outperformed traditional markers such as body mass index and serum albumin levels, particularly in patients with solid tumors ( 14 ). A novel prognostic tool including PNI alongside clinical variables has also been proposed to enhance personalized outcome predictions. For breast cancer patients, the CONUT score may serve as a reliable and clinically meaningful predictor of survival for cancer patients. Its significance lies in its accessibility, simplicity, and prognostic relevance ( 15 ). Moreover, in both early and advanced stages of breast cancer, patients with higher PNI values exhibited significantly longer survival periods. Pretreatment PNI, due to its convenient, noninvasive, and reproducible nature, has shown promise as a prognostic biomarker, particularly for patients undergoing neoadjuvant chemotherapy, and may inform treatment planning and decision-making processes ( 17 ). To enhance the early detection and management of nutritional and metabolic abnormalities in cancer patients, implementing effective nutritional risk screening is essential. One critical aspect to consider is the patient's overall condition when selecting appropriate nutritional assessment tools. The core challenge lies not only in raising awareness or conducting regular follow-ups on patients’ nutritional needs but in turning these requirements into actionable and sustainable interventions on ground. This is particularly relevant in resource-limited settings, where food and basic necessities are often distributed inequitably. In such environments, the capacity to adequately address and manage nutritional needs depends largely on what is immediately available with very limited resources or sometimes nothing actually to have. Therefore, practical application of nutritional requirements must precede ongoing monitoring, discussion, and evaluation of patients’ clinical and nutritional status. Conclusion In resource-limited settings, addressing the nutritional needs of cancer patients presents a significant challenge. While tools like PNI and CONUT offer valuable, low-cost methods for assessing prognosis and nutritional status especially for solid tumors, for PNI, it provides useful prognostic information independently in cancer patients. The real barrier lies in applying nutritional interventions on the ground due to restricted access to resources and healthcare services. Greater attention must be given to implementing practical nutritional support strategies alongside regular clinical assessments to ensure a holistic approach to cancer care in such environments. The results of this study have demonstrated that PNI is an easy-to-use nutrition assessment tool in the assessment of nutritional status of cancer patients and provides useful prognostic information in cancer patients. Abbreviations Augusta Victoria Hospital (AVH) Al Ahli Arab Hospital (AAH) Body Mass Index (BMI) Prognostic Nutritional Index (PNI) Controlling Nutritional Status (CONUT) Tumor's size, lymph node, metastases (TNM) Patient-Generated Subjective Global Assessment (PG-SGA) Overall survival (OS) Ethylene diamine tetra-acetic acid (EDTA) Complete Blood Count (CBC) Albumin (ALB) Lactate Dehydrogenase (LDH) Creatine Kinase (CK) Statistical Package for the Social Sciences (SPSS) Noncommunicable diseases (NCDs) Intravenously (IV) Declarations Ethics approval and consent to participate: Helsinki Committee approval was obtained before starting the study. Permission was obtained from the Ethical Committee of the Augusta Victoria Hospital for this research. Informed consent was obtained orally and by consent from all participants to undergo this study and collect data and blood samples for analysis after explaining the aim and objectives of the study. Consent for publication: Not applicable. Availability of data and materials: The data collected was with authors, supplied as separated file. Competing Interests: Authors declare that they do not have any conflict of interest. Funding: We received no funding. Authors' contributions: We have reviewed and approved the submitted cross sectional study for publication. We organized the data, design, data analysis, and discussion, added some notes according to actual experiences during Gaza War 2023/2024 at Ahli Arab Hospital, and wrote the article. Acknowledgements: We extend our appreciation to our friends and colleagues, who have been supportive throughout this effort. References WHO, Organization WH. Cancer, 2024, https://www.who.int/health-topics/cancer#tab=tab_1 Correa-Rodríguez M, Pocovi-Gerardino G, Callejas-Rubio JL, Fernández RR, Martín-Amada M, Cruz-Caparros MG, Ortego-Centeno N, Rueda-Medina B. The Prognostic Nutritional Index and Nutritional Risk Index Are Associated with Disease Activity in Patients with Systemic Lupus Erythematosus. Nutrients. 2019;11(3):638. 10.3390/nu11030638 . PMID: 30884776; PMCID: PMC6471040. Zhang Q, Zhang K, Li X, Zhang X, Song M, Liu T, Shi. H. P. A novel model with nutrition-related parameters for predicting overall survival of cancer patients. Support Care Cancer. 2021;29(11):6721–30. Rosen RD, Sapra A. TNM classification. In StatPearls [Internet]. StatPearls Publishing; 2023. Kanesvaran R, Li H, Koo KN, Poon D. Analysis of prognostic factors of comprehensive geriatric assessment and development of a clinical scoring system in elderly Asian patients with cancer. J Clin Oncol. 2011;29:3620–7. Martin L, Watanabe S, Fainsinger R, Lau F, Ghosh S, Quan H, Atkins M, Fassbender K, Downing GM, Baracos V. Prognostic factors in patients with advanced cancer: use of the patient-generated subjective global assessment in survival prediction. 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The latter process is called metastasizing and is a major cause of death from cancer. A neoplasm and malignant tumor are other common names for cancer and considered as the second leading cause of death in the globe (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNutritional status has been widely correlated with the initiation and prognosis of cancer (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). There is growing evidence that a patient's nutritional state may have an impact on their prognosis from cancer. Stratifying patients into distinct risk groups (score\u0026thinsp;\u0026lt;\u0026thinsp;18.5 and \u0026ge;\u0026thinsp;18.5) for each TNM category revealed significantly varied median overall survival rates (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e); this approach was created to help physicians' stage various cancer types according to established standards. The tumor's size (T), its degree of lymph node dissemination (N), and the existence of metastases (M) are all included in the TNM Staging System (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIndividuals with cancer are frequently diagnosed with cancer-associated malnutrition, which has factors connected to the individuals' unique lifestyles, the cancerous tumor, and the course of treatment. Despite the fact that malnutrition is a global issue linked to higher rates of morbidity, death, and expense, there hasn't been agreement on diagnostic standards in clinical settings (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe survival and duration of treatment for cancer patients are strongly correlated with their nutritional health; as a result, several prognostic models incorporate information on nutrition (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), and earlier research had developed predictive models for cancer patients using the Patient-Generated Subjective Global Assessment (PG-SGA) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). A professional evaluation component (which includes weight change, diseases related to diet, metabolic demand, and physical examination) and a patient-reported component (which includes weight, food consumption, symptoms, and activities and function) are both included in the PG-SGA (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) Score have been recently used as useful screening tools to describe the prognosis of many diseases in patients, including cancer (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Anti-cancer therapy's primary goal is to improve patients' overall survival (OS), hence factors that indicate prognosis are of clinical and scientific significance (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAs malnutrition is well known to be closely associated with poor survival in patients with cancer, evaluation of nutritional status using nutritional markers has attracted attention in the context of survival outcomes of cancer patients. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Malnutrition, a sub-acute or chronic state in cancer patients, may impair immune function and increase susceptibility to infection and complications of the treatment, thus leading to an increased mortality of cancer patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design \u0026amp; Study Population:\u003c/h2\u003e\u003cp\u003eA cross-sectional study was conducted among 100 subjects diagnosed with cancer who attended the Outpatient Oncology Clinic of Augusta Victoria Hospital (AVH) at Al Ahli Arab Hospital (AAH) in the Gaza Strip, State of Palestine, from September 2024 to December 2024.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSampling Methods and Processing:\u003c/h3\u003e\n\u003cp\u003e\u003cb\u003eQuestionnaire interview\u003c/b\u003e: A questionnaire administered to patients: general information, socioeconomic data, family history, medical history, and therapeutic plan data related to cancer patients will be collected.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSample collection\u003c/strong\u003e\u003cp\u003eVenous blood samples were collected. A 5 ml syringe was used to withdraw about 4 ml of venous blood from all study participants using the venipuncture technique under quality control and safety procedures. Two ml of the collected blood was placed into sterile ethylene diamine tetra-acetic acid (EDTA) tubes for hematology testing (CBC). Two milliliters were delivered into a plain tube for chemistry and special tests. Serum and plasma were obtained from both tubes after centrifugation at 3500 rpm for 5 minutes for use in kidney function tests, liver function tests, lipid profile, LDH, CK, and ALB preparation. Serum samples were stored at 2\u0026ndash;8\u0026deg;C if analysis was performed within 24 hours after collection; otherwise, they were stored at -20\u0026deg;C until analysis.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e Quality assessment procedures of pre-analytical, analytical, and post-analytical phases were applied to ensure a suitable assurance method was followed to maintain testing accuracy. All levels of controls for CBC and chemical tests were used to establish high quality across all tests throughout the research period and procedures. Internal and external quality control measures were also applied to manage the data and results.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eThe data entry was conducted on an exact basis by the researcher. The data accuracy was checked, and there were no missing values while filling out the data. Data was coded as needed before proceeding with the statistical analysis and cleaned for any illogical or error values. The researcher then used SPSS version 26 statistical tools to analyze the data.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study sample involved 100 individuals whose mean age was 50.16 years (\u0026plusmn;\u0026thinsp;14.50); 71% of participants were female, 66% of whom were married, and 19% were single. With a mean weight loss during the war of 15.3 kg (\u0026plusmn;\u0026thinsp;5.4) and a mean BMI of 23.45 (\u0026plusmn;\u0026thinsp;4.9), the northern Gaza Strip accounts for 70% of the population. Over the period of the preceding four months, from 1st December 2024 to 31st March 2025, 9% of attending patients in the Outpatient Oncology Clinic of Augusta Victoria Hospital at Al Ahli Arab Hospital lost their lives regarding their specific kind of cancer as a result of overall malnutrition conditions in the Gaza Strip due to war circumstances. 55% of them have been diagnosed as having breast cancer, 16% have colon cancer, 15% have thyroid cancer, 7% have prostate cancer, and 7% have another solid malignancy. Everyone whose participating carried out the established questionnaire and underwent specific laboratory testing.\u003c/p\u003e\u003cp\u003eBased on the details obtained through the questionnaire, 63% of respondents had at least one family member diagnosed with cancer; around 52.38% of them have the same type of cancer, whereas 47.61% have a different type. However, 42% are related to first-degree relatives. 10% of patients stop taking their medications due to doctor consultation, and 68% stop for more than a year, according to war conditions. Both patients require additional follow-up and an oncology professional to handle their status, but during specific periods during the war, they were unable and struggling to communicate with their doctor until an international organization was able to provide some types of medications but not cover all the types of malignancies, even if they were administered intravenously (IV) or as tablets. 10% of them continue to take their medications and require ongoing monitoring during the course of therapy and management, whereas 12% of them take their medication and then stop for follow-up under medical observation. Of these patients, 25% just received surgical treatment, 48% had non-surgical treatment, including 26% who were chemotherapy-dependent, and 27% received both surgical and nonsurgical treatment.\u003c/p\u003e\u003cp\u003eAccording to their nutritional behaviors or dietary intake within this period of time, 81% of them only eat once a day if there is a meal available; even then, they might skip meals for a certain amount of time. After this, all civilians began receiving emergency assistance from international humanitarian organizations. This led to a modification in the patients' food intake and quality; 15% of the participants eat almost twice or three times a day, 68% of patients arrived at the clinic with complaints that required further investigation and an oncologist consultation, 17% of patients had hypertension (HTN), 6% had diabetes mellitus (DM), and 6% had both conditions.\u003c/p\u003e\u003cp\u003eThe prognostic nutritional index (PNI) indicates that 66% of patients have a good prognosis status because of the nature of the malignancy, which offers a favorable prognosis condition; 34% of patients have a poor prognosis. Male patients had a worse prognosis status than female patients, which was statistically significant (P value\u0026thinsp;=\u0026thinsp;0.017). Additionally, there was a statistically significant correlation between the type of malignancy and the PNI score (P\u0026thinsp;=\u0026thinsp;0.002). However, based on CONUT scoring and associated index interpretation, 89% of patients show normal nutritional status following an initial intake of better fortified food and supplements presented as emergency and humanitarian aid supplies, but 4% are still at mild nutritional risk and 7% are at moderate nutritional risk. Clinically significant differences were shown among patients in the north and south (P\u0026thinsp;=\u0026thinsp;0.022), as well as among patients who are still alive and those who have passed away (P\u0026thinsp;=\u0026thinsp;0.001) and those who have different types of cancer (P\u0026thinsp;=\u0026thinsp;0.006). The non-surgical therapy options revealed a statistically significant picture for relations with the COUNT index (P\u0026thinsp;=\u0026thinsp;0.02), in addition to their latest therapy dose (P\u0026thinsp;=\u0026thinsp;0.001), whatever the cause of medication termination.\u003c/p\u003e\u003cp\u003eA statistically significant difference was observed based on the last therapy dose variable (F (2.97)\u0026thinsp;=\u0026thinsp;6.5, p\u0026thinsp;=\u0026thinsp;0.002), the type of cancer (same or different) (F (2.97)\u0026thinsp;=\u0026thinsp;3.4, p\u0026thinsp;=\u0026thinsp;0.037), family history (F (2.97)\u0026thinsp;=\u0026thinsp;3.76, p\u0026thinsp;=\u0026thinsp;0.027), and geographic location (south or north) (F (2.97)\u0026thinsp;=\u0026thinsp;3.98, p\u0026thinsp;=\u0026thinsp;0.022) in a one-way ANOVA that examined the differences in nutritional risk groups according to a number of clinical and demographic variables. The normal nutritional risk group and the mild nutritional risk group differed significantly (p\u0026thinsp;=\u0026thinsp;0.002) for the last therapeutic dose variable, based on Tukey's post hoc analysis. Statistically significant differences were observed between the mild and moderate nutritional risk groups (p\u0026thinsp;=\u0026thinsp;0.046) and between the normal and mild nutritional risk groups (p\u0026thinsp;=\u0026thinsp;0.022) with regards to the family history variable. The mild and moderate nutritional risk groups differed significantly (p\u0026thinsp;=\u0026thinsp;0.032) in the particular type of cancer-associated variable (same or different with patient's disease). Finally, statistically significant differences between the moderate and mild nutritional risk groups (p\u0026thinsp;=\u0026thinsp;0.033) and between the moderate and normal nutritional risk groups (p\u0026thinsp;=\u0026thinsp;0.040) were observed for the location-based variable.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe exceptional and challenging circumstances resulting from the ongoing war in Gaza have posed significant barriers to the healthcare system, particularly affecting vulnerable groups such as patients with noncommunicable diseases (NCDs), children, the elderly, and others with cancer. These unique conditions hinder the ability to compare our findings and those reported in another research. In this paper, we aimed to assess the prognostic value of the PNI and CONUT indices within a severely resource-limited environment. Although the study\u0026rsquo;s constraints, such as a limited data collection period and a relatively small sample size, may affect the final results, these limitations are inherent to the ongoing humanitarian crisis and require further research to clarify. Due to movement restrictions and safety concerns, patient access and data collection were considerably restricted. Nevertheless, the available data were utilized to conduct this analysis. To the best of the authors\u0026rsquo; knowledge, there is currently no comparable study in the literature that has evaluated these prognostic markers under similar conditions.\u003c/p\u003e\u003cp\u003eUnexplained weight loss is a well-known indicator of cancer progression and is commonly recognized as a marker of malnutrition status. In the context of our study, which was conducted during the war circumstances, the average weight loss observed was 15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 kg, highlighting the severity of nutritional deterioration under such circumstances. While treatment-related side effects, particularly those associated with chemotherapy, such as nausea, mucositis, vomiting, and altered taste change, are known contributors to malnutrition in cancer patients, this factor was less significant in our cohort. The majority of patients had temporarily discontinued their cancer treatment due to the war, limiting the direct impact of treatment-related nutritional decline in our sample.\u003c/p\u003e\u003cp\u003eMalnutrition in our study was primarily associated with reduced food intake and altered energy expenditure, compounded by the challenges of displacement, inadequate shelter, and poor hygiene conditions. These findings are consistent with previous research indicating that elderly cancer patients are particularly vulnerable to malnutrition due to physiological, behavioral, economic, and environmental factors (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Additionally, both our data and prior studies suggest a higher prevalence of malnutrition among male cancer patients compared to females. This may be partially explained by sociocultural factors specific to Arabic culture, where women often remain at home and receive greater familial support, potentially improving their nutritional intake and stability (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Given these findings, it is imperative to implement routine nutritional assessments for all cancer patients throughout the treatment process. Early identification and management of malnutrition, in collaboration with oncologist consultation, are essential for improving outcomes and quality of life in this vulnerable population (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePNI has emerged as a reliable independent prognostic indicator across various cancer types. Elevated PNI levels have been consistently associated with improved clinical outcomes, including in subgroups stratified of solid tumors (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Specifically, a CONUT score\u0026thinsp;\u0026gt;\u0026thinsp;3 or PNI\u0026thinsp;\u0026le;\u0026thinsp;47.7 was indicative of an unfavorable prognosis (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), although in other studies, the CONUT score failed to retain predictive value (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In elderly cancer patients, PNI has demonstrated a significant correlation with overall survival, suggesting its potential as a valuable, inexpensive prognostic tool. Given the increasing rate of cancer in aging populations, such accessible and practical biomarkers are essential to guide treatment strategies and optimize healthcare (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Furthermore, high PNI values have been associated with improvement of responses to anti-cancer therapies and have outperformed traditional markers such as body mass index and serum albumin levels, particularly in patients with solid tumors (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). A novel prognostic tool including PNI alongside clinical variables has also been proposed to enhance personalized outcome predictions.\u003c/p\u003e\u003cp\u003eFor breast cancer patients, the CONUT score may serve as a reliable and clinically meaningful predictor of survival for cancer patients. Its significance lies in its accessibility, simplicity, and prognostic relevance (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Moreover, in both early and advanced stages of breast cancer, patients with higher PNI values exhibited significantly longer survival periods. Pretreatment PNI, due to its convenient, noninvasive, and reproducible nature, has shown promise as a prognostic biomarker, particularly for patients undergoing neoadjuvant chemotherapy, and may inform treatment planning and decision-making processes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTo enhance the early detection and management of nutritional and metabolic abnormalities in cancer patients, implementing effective nutritional risk screening is essential. One critical aspect to consider is the patient's overall condition when selecting appropriate nutritional assessment tools. The core challenge lies not only in raising awareness or conducting regular follow-ups on patients\u0026rsquo; nutritional needs but in turning these requirements into actionable and sustainable interventions on ground. This is particularly relevant in resource-limited settings, where food and basic necessities are often distributed inequitably. In such environments, the capacity to adequately address and manage nutritional needs depends largely on what is immediately available with very limited resources or sometimes nothing actually to have. Therefore, practical application of nutritional requirements must precede ongoing monitoring, discussion, and evaluation of patients\u0026rsquo; clinical and nutritional status.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn resource-limited settings, addressing the nutritional needs of cancer patients presents a significant challenge. While tools like PNI and CONUT offer valuable, low-cost methods for assessing prognosis and nutritional status especially for solid tumors, for PNI, it provides useful prognostic information independently in cancer patients. The real barrier lies in applying nutritional interventions on the ground due to restricted access to resources and healthcare services. Greater attention must be given to implementing practical nutritional support strategies alongside regular clinical assessments to ensure a holistic approach to cancer care in such environments. The results of this study have demonstrated that PNI is an easy-to-use nutrition assessment tool in the assessment of nutritional status of cancer patients and provides useful prognostic information in cancer patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAugusta Victoria Hospital (AVH)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAl Ahli Arab Hospital (AAH)\u003c/p\u003e\n\u003cp\u003eBody Mass Index (BMI)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrognostic Nutritional Index (PNI)\u003c/p\u003e\n\u003cp\u003eControlling Nutritional Status (CONUT)\u003c/p\u003e\n\u003cp\u003eTumor\u0026apos;s size, lymph node, metastases (TNM)\u003c/p\u003e\n\u003cp\u003ePatient-Generated Subjective Global Assessment (PG-SGA)\u003c/p\u003e\n\u003cp\u003eOverall survival (OS)\u003c/p\u003e\n\u003cp\u003eEthylene diamine tetra-acetic acid (EDTA)\u003c/p\u003e\n\u003cp\u003eComplete Blood Count (CBC)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlbumin (ALB)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLactate Dehydrogenase (LDH)\u003c/p\u003e\n\u003cp\u003eCreatine Kinase (CK)\u003c/p\u003e\n\u003cp\u003eStatistical Package for the Social Sciences (SPSS)\u003c/p\u003e\n\u003cp\u003eNoncommunicable diseases (NCDs)\u003c/p\u003e\n\u003cp\u003eIntravenously (IV)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHelsinki Committee approval was obtained before starting the study. Permission was obtained from the Ethical Committee of the Augusta Victoria Hospital for this research. Informed consent was obtained orally and by consent from all participants to undergo this study and collect data and blood samples for analysis after explaining the aim and objectives of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data collected was with authors, supplied as separated file.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare that they do not have any conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe received no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have reviewed and approved the submitted cross sectional study for publication. We organized the data, design, data analysis, and discussion, added some notes according to actual experiences during Gaza War 2023/2024 at Ahli Arab Hospital, and wrote the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extend our appreciation to our friends and colleagues, who have been supportive throughout this effort.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWHO, Organization WH. 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Annals Palliat Med. 2021;10(11):116351642\u0026ndash;116311642.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerreira AF, Fernandes T, Carvalho MDC, Loureiro HS. The prognostic role of Prognostic Nutritional Index and controlling nutritional status in predicting survival in older adults with oncological disease: a systematic review. Onco. 2024;4(2):101\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYan X, Wang J, Mao J, Wang Y, Wang X, Yang M, Qiao H. Identification of prognostic nutritional index as a reliable prognostic indicator for advanced lung cancer patients receiving immune checkpoint inhibitors. Front Nutr. 2023;10:1213255.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu M, Chen L, Kong X, Wang X, Ren Y, Liu Q, Wang J. Controlling nutritional status (CONUT) as a novel postoperative prognostic marker in breast cancer patients: a retrospective study. Biomed Res Int, 2022(1), 3254581.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eM\u0026uuml;ller L, Hahn F, M\u0026auml;hringer-Kunz A, Stoehr F, Gairing SJ, Foerster F, Kloeckner R. Immunonutritive scoring in patients with hepatocellular carcinoma undergoing transarterial chemoembolization: prognostic nutritional index or controlling nutritional status score? Front Oncol. 2021;11:696183.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen L, Bai P, Kong X, Huang S, Wang Z, Wang X, Wang J. Prognostic nutritional index (PNI) in patients with breast cancer treated with neoadjuvant chemotherapy as a useful prognostic indicator. Front cell Dev biology. 2021;9:656741.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Nutritional index, Cancer patient, war area, Prognosis assessment","lastPublishedDoi":"10.21203/rs.3.rs-7398900/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7398900/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo evaluate the usefulness of nutritional index and disease risk index in prognosis of cancer patients.\u003c/p\u003e\u003ch2\u003eMethodology:\u003c/h2\u003e\u003cp\u003eA cross-sectional study was conducted among 100 subjects diagnosed with cancer who attended the Outpatient Oncology Clinic of Augusta Victoria Hospital (AVH) at Al Ahli Arab Hospital (AAH) in the Gaza Strip, State of Palestine, from September 2024 to December 2024.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e100 participants in the study had a mean age of 50.16 years (\u0026plusmn;\u0026thinsp;14.50); their mean weight loss during the war was 15.3 kg (\u0026plusmn;\u0026thinsp;5.4), and their BMI was 23.45 (\u0026plusmn;\u0026thinsp;4.9). 63% of the participants had at least one family member with cancer, and 42% of them were related to first-degree relatives. 81% of participants only eat once a day if there is a meal present or they may skip meals for a while. 68% of patients complain and require medical assessment by an oncologist. Male patients had a worse prognosis status than female patients. According to the PNI, which shows that 66% of patients have a good prognosis while 34% have a poor prognosis status due to extremely hard conditions. Based on PNI and CONUT scoring interpretations, there was a statistically significant correlation between the type of malignancy and the PNI score (P\u0026thinsp;=\u0026thinsp;0.002), and there were clinically significant disparities related to location variable (P\u0026thinsp;=\u0026thinsp;0.022).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eTools like PNI and CONUT offer valuable, low-cost methods for assessing prognosis and nutritional status, especially for solid tumors. PNI could be used as an independent prognostic indicator for cancer status, while more studies are needed to assess the prognostic role of CONUT.\u003c/p\u003e","manuscriptTitle":"Evaluating the Usefulness of the Prognostic Nutritional Index and Controlling Nutritional Status in Stratifying Prognosis in Cancer Patients during Gaza War, 2024","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-26 14:53:06","doi":"10.21203/rs.3.rs-7398900/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-10-03T10:23:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"252672148606763878056958776506958432341","date":"2025-10-03T10:01:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T09:46:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-02T19:20:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-30T03:48:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"60853364467037897166680953131464546621","date":"2025-09-27T12:24:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124194668352352588911228314873967848872","date":"2025-09-24T16:16:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2698047364775225766947471039301450337","date":"2025-09-17T14:52:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-17T14:46:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-17T04:55:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-27T12:47:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-27T12:31:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-08-27T12:28:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6512cbf6-72bb-40f2-8800-25c1f60caff4","owner":[],"postedDate":"September 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-26T14:53:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-26 14:53:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7398900","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7398900","identity":"rs-7398900","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}