Real-world comparative effectiveness of FOLFIRINOX versus gemcitabine/nab-paclitaxel in metastatic pancreatic cancer: prognostic impact of metastatic site and burden in a Middle Eastern cohort

Introduction

Pancreatic cancer (PC) is one of the most aggressive and fatal cancers, with poor prognosis and limited treatment options. Worldwide, it is the seventh leading cause of cancer death and is projected to become the second most common cause of cancer-related death in the United States by 2030. Despite advances in oncology, the 5-year survival rate for PC remains very low at about 9%, indicating the urgent need for improved early detection and treatment strategies (1,2).

Over the past several decades, the global rates of PC diagnosis and death have nearly doubled, highlighting its increasing burden on public health systems (3). In Saudi Arabia, the incidence of PC has risen significantly, with reported cases quadrupling between 1990 and 2016. Because of this increase, PC is now a top health care priority in the kingdom. Epidemiologically, the disease mainly affects older adults, with more than 85% of cases diagnosed in individuals aged 50 years and older (4).

Surgical resection remains the only potentially curative treatment for PC. However, because the disease often progresses without symptoms and is diagnosed at a late stage, fewer than 20% of patients are eligible for surgery at diagnosis. For most patients with unresectable or metastatic disease, systemic chemotherapy is the main treatment option (2). In the past, gemcitabine monotherapy was the standard treatment for advanced PC, giving patients a small survival benefit. However, recent clinical evidence favors combination chemotherapy regimens that have proven more effective. Two such regimens—FOLFIRINOX (FFX), which includes fluorouracil, leucovorin, irinotecan, and oxaliplatin, and gemcitabine plus nab-paclitaxel (GnP)—have become first-line treatments, showing improved response rates and survival outcomes compared to monotherapy (5).

While randomized trials and extensive retrospective cohorts from Western and East Asian populations have assessed the comparative efficiency of FFX and GnP, patients from the Middle East are significantly underrepresented in these studies (6,7). Variations in demographic characteristics, comorbidity patterns, treatment selection methodologies, access to oncology services, and referral patterns may affect both regimen selection and clinical results, limiting the applicability of current data to this region. Thus, empirical evidence from standard therapeutic practice in Middle Eastern populations is essential to contextualize and corroborate previous findings.

Treating elderly patients with PC involves unique clinical challenges. Advanced age often comes with comorbid conditions, decreased physiological reserve, and poor performance status, which can limit tolerance to aggressive chemotherapy. Therefore, optimizing methods of treatment for this susceptible group necessitates a careful balance between maximizing effectiveness and reducing toxicity. Personalized treatment choices and the availability of well-tolerated options are key to improving outcomes in older adults with PC (8).

Along with regimen effects, the burden of metastatic disease, which includes the number of metastatic sites and the site of the metastases (liver, lung, peritoneum, lymph nodes), has been identified as a key prognostic factor in PC (9). The liver is the most common site of early distant metastasis with frequent progression to one or multiple other sites, such as lungs, peritoneum, bone, adrenals, and brain (10). A recent retrospective study has demonstrated differential survival depending on the metastatic site. Specifically, patients with lung-only metastases have significantly longer survival compared to those with liver metastasis (11).

The number of metastases in PC is an independent factor that negatively impacts survival. Patients with multiple metastatic sites have worse overall survival (OS) than those with solitary metastases. Different metastatic sites also represent various OS (12). Stratification by site and burden has the potential to refine prognostic modeling and inform therapeutic decision-making, given the heterogeneity of metastatic patterns.

Despite this, a limited number of real-world studies have simultaneously assessed first-line chemotherapy regimens while including comprehensive metastatic sites and burden data into prognostic models. This disparity is especially pertinent in the Middle East, where genetic, demographic, and practice-pattern variations may affect metastatic presentation and treatment outcomes; yet, region-specific comparative data are limited. Thus, this retrospective study aimed to evaluate and compare the clinical outcomes and safety profiles of two standard first-line chemotherapy regimens, FFX and GnP, in patients with locally advanced or metastatic PC. This study aims to derive significant insights into the relative efficacy and tolerability of these treatment options by examining real-world data from routine clinical practice, beyond the confines of controlled trial environments.

The specific objectives were to (I) compare the objective response rate (ORR) and disease control rate (DCR) between the FFX and GnP groups; (II) evaluate OS and progression-free survival (PFS) associated with each regimen; and (III) study the prognostic value of site-specific metastases and their number. This analysis seeks to guide therapeutic decision-making in advanced PC, especially in cases where patient comorbidities, performance status, and treatment tolerability need to be carefully balanced. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-913/rc).

Methods

Study design and population

This retrospective, comparative effectiveness study was conducted at the International Medical Center (IMC) in Jeddah, Saudi Arabia. Medical records of adult patients with locally advanced or metastatic PC who received either modified FFX or GnP as first-line chemotherapy from January 2019 to January 2024 were reviewed. Follow-up data, including OS, defined as the time from the start of therapy to death, and PFS, defined as the time from the start of treatment to radiologic or clinical progression or death, were collected through July 2024. The eligibility criteria for both treatments included age over 18 years, histologically confirmed locally advanced or metastatic PC, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, no prior systemic chemotherapy for advanced disease, adequate hematologic, hepatic, and renal functions, and no history of secondary primary malignancy. Patients who did not have an evaluable tumor response or were lost to follow up immediately after starting treatment were excluded. Demographic, clinical, and laboratory data were collected from the hospital’s electronic medical records system. Variables included age, sex, smoking status, tumor location, baseline CA19-9 levels, imaging findings, and treatment outcomes.

Treatment regimen

The FFX regimen included oxaliplatin (85 mg/m²), leucovorin (400 mg/m²), irinotecan (180 mg/m²), and 5-fluorouracil [400 mg/m² intravenous (IV) bolus followed by 2,400 mg/m² continuous infusion over 46 hours], administered every 2 weeks.

The GnP regimen consisted of gemcitabine (1,000 mg/m²) and nab-paclitaxel (125 mg/m²), given on days 1, 8, and 15 of a 28-day cycle. All patients received granulocyte colony-stimulating factor (G-CSF) prophylactically (3–5 doses per cycle, starting 48 hours after chemotherapy) to reduce the risk of neutropenia. Dose reductions (10–30%) were allowed based on individual tolerability and clinician judgment. Treatment was discontinued when there was evidence of disease progression or the occurrence of life-threatening adverse events.

Assessment of efficacy and safety

For every patients, baseline staging was performed using ¹⁸F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) following standardized patient preparation and uniform acquisition parameters, with consistent scanner setting and weight-based injected activity. PET/CT findings were evaluated qualitatively (visual assessment of the intensity, extent, and number of metabolically active primary and metastatic lesions) and quantitatively using standardized uptake values (SUVs), along with morphologic assessment from the CT component.

Tumor response was evaluated every 8 weeks using ¹⁸F-FDG PET/CT, contrast-enhanced CT or magnetic resonance imaging studies, according condition of the patient and the laboratory findings, considering the financial impact. The studies were interpreted by specialized nuclear medicine physician and radiologists blinded to treatment allocation according to RECIST V1.1. Final clinical assessments were independently performed by treating oncologists. Adverse events were recorded and graded using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.0.

Ethical considerations

The study protocol was approved and reviewed by the Institutional Review Board (IRB) of the IMC in Jeddah, Saudi Arabia (IRB approval No. 2024-02-236). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Informed consent for chemotherapy was obtained from all enrolled patients. The consent was signed by the patient after explaining the treatment’s side effects. Written informed consent for the publication was also obtained.

Statistical analysis

All analyses were performed using IBM SPSS Statistics, version 29 (IBM Corp., Armonk, NY, USA). A two-sided P value of less than 0.05 was deemed statistically significant. The Shapiro-Wilk test was used for finding outliers and the shape of the distribution in continuous variables. The continuous variables did not follow a normal distribution, so they are summarized as the median [interquartile range (IQR)] and compared between regimens using the Mann-Whitney U test. Categorical variables are displayed as n (%) and analyzed using Pearson’s χ² or Fisher’s exact test when expected counts are less than 5.

Kaplan-Meier curves for OS and PFS were created and compared across regimens using the log-rank (Mantel-Cox) test; medians with 95% confidence intervals (CIs) were presented. To determine which characteristics correlated with OS and PFS, we initially employed univariable Cox proportional hazards models for each potential predictor. Variables exhibiting P<0.10 in univariable analysis and/or significant clinical relevance were incorporated into a multivariable Cox model. The results are presented as hazard ratios (HRs) accompanied by 95% CIs.

For descriptive Kaplan-Meier analyses, the metastatic location was categorized into five groups: liver, lung, lymph node, peritoneal, and multiple. The original five categories (1, 2, 3, 4, and ≥5) of the number of metastatic were kept to illustrate an entire spectrum of disease burden. However, to avoid model overfitting and instability from sparse cells given the low number of events, we prespecified pragmatic recoding of certain predictors: the site of metastasis (original levels: liver, lung, lymph node, peritoneal, multiple) was reclassified into three categories: liver, lung, and other (lymph node, peritoneal, or multiple). This procedure resolved the issue of quasi-complete separation and the very large standard errors that were observed when all uncommon levels were included. Additionally, it reduced parameters in relation to events while maintaining clinically meaningful contrasts. The number of metastatic locations was also recorded as 1 vs. ≥2 (single vs. numerous) to reduce sparsity at higher counts and to represent how doctors usually group patients. These regroupings were utilized exclusively in multivariable Cox models; comprehensive, disaggregated distributions continue to be shown in descriptive tables and Kaplan-Meier summaries to maintain clinical relevance.

Results

Patient disposition

A total of 110 patients diagnosed with pancreatic ductal adenocarcinoma were initially screened. After an eligibility assessment, 92 met the predefined inclusion criteria. Of these, 25 patients discontinued treatment due to adverse events, loss of follow-up, or transfer to another treatment center. Ultimately, 67 patients were enrolled, with 60 completing the full study protocol and included in the final comparative analysis. Figure 1 summarizes the distribution and attrition of patients throughout the study phases.

Figure 1 Flowchart of patient enrollment and study disposition. FFX, FOLFIRINOX; GnP, gemcitabine plus nab-paclitaxel.

Demographic, disease and treatment characteristics of study populations

This study included a total of 60 patients with metastatic PC. Most of the participants were male, had high-grade tumors (grade III, 60%), and had an excellent performance status (ECOG 0–1), with a median age of 59.5 years. The predominant site of the original tumor was the body of the pancreas (50%), followed by the head (18%). The liver, lung, and lymph nodes were the most frequently encountered metastatic sites. FFX was administered to 60% of patients, while GnP was administered to 40%. The overall response rate (complete + partial) was 70%, and the median treatment duration was 4 months. Anemia (33%), thrombocytopenia (23%), and neuropathy (28%) were the most frequently observed toxicities. The median PFS and OS were 8.5 and 5 months, respectively (Table S1).

The primary demographic and clinical characteristics of patients administered FFX and GnP were largely similar across the groups. There were no significant changes in age, sex distribution, ECOG performance status, or disease-related factors such as tumor grade, primary tumor site, and metastatic pattern. Patients receiving FFX had significantly more treatment cycles and had a slightly longer treatment duration compared to those on GnP (P=0.001 and P=0.041, respectively) (Table 1).

Treatment toxicities and response between regimens

The treatment-related toxicities were generally manageable in both groups (Table 2). In comparison to patients who received FFX, patients who received GnP experienced significantly more hematologic adverse events, such as anemia and thrombocytopenia (P=0.045 and P=0.01, respectively). Peripheral neuropathy was also more prevalent in the GnP group (P=0.01). Tumor response was categorized according to RECIST criteria as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). We characterized the ORR as CR + PR and the DCR as CR + PR + SD. In comparison to GnP, FFX exhibited a higher ORR (71.4% vs. 28.6%, P=0.006) and DCR (68.1% vs. 31.9%, P=0.01) in terms of treatment response (Table 3).

To further evaluate the patterns of response, we presented three representative cases in our study, as shown in Figure 2:

• Case 1: the baseline scan shows a large hypermetabolic pancreatic mass. The follow-up scan indicates a decrease in both size and metabolic activity, consistent with a PR (Figure2A,2B).
• Case 2: the baseline scan shows a hypermetabolic pancreatic lesion with hepatic metastasis. The follow-up scan reveals a slight increase in lesion size and metabolic activity, along with progression in hepatic metastases, indicating overall disease progression (Figure 2C,2D).
• Case 3: the baseline scan reveals a hypermetabolic pancreatic mass. The follow-up scan shows complete regression, indicating a positive imaging response (Figure 2E,2F).

Figure 2 Axial fused PET/CT images of three cases in the study showing different tumor responses. Case 1: (A) baseline hypermetabolic pancreatic mass, (B) follow-up showing partial response. Case 2: (C) baseline pancreatic lesion with hepatic metastasis, (D) follow-up showing progression. Case 3: (E) baseline pancreatic mass, (F) follow-up showing complete regression. CT, computed tomography; PET, positron emission tomography.

Survival outcomes (OS and PFS) between regimens

The Kaplan-Meier analysis indicated similar survival outcomes for both therapies (Table 4). In both therapy groups, the median overall OS and PFS was 9.0 months. There was no statistically significant difference in OS and PFS between the regimens (OS: P=0.15; PFS: P=0.13) (Figure 3).

Figure 3 Kaplan-Meier survival curves comparing FFX and GnP regimens: (A) overall survival (log-rank P=0.15) and (B) progression-free survival (log-rank P=0.13). FFX, FOLFIRINOX; FOLFIRINOX, fluorouracil, leucovorin, irinotecan, and oxaliplatin; GnP, gemcitabine plus nab-paclitaxel.

Survival outcomes (OS and PFS) based on metastasis site

The metastatic site significantly affected the survival outcomes for both OS and PFS. Patients who had liver metastases experienced the worst outcomes, with a mean OS of 7.5±0.41 months and a mean PFS of 4.3±0.27 months. In contrast, patients with lymph node or multiple metastatic sites exhibited longer survival durations (mean OS =13.0±0.71 months and 14.5±0.98 months; mean PFS =10.5±1.06 months and 11.0±0.83 months, respectively) (Table 5). Right-censoring prevented the calculation of median survival estimates for all subgroups; consequently, mean values were reported. The statistically significant variation across metastatic sites for both OS (P=0.031) and PFS (P=0.006) was confirmed by log-rank testing (Figure 4A,4B). Kaplan-Meier curves demonstrate that patients with hepatic involvement experience earlier disease progression and mortality than those with nodal or multiple-site metastases.

Figure 4 Kaplan-Meier survival curve according to site of metastasis: (A) overall survival curves (log-rank P=0.03) and (B) progression-free survival curves (log-rank P=0.006).

Survival outcomes (OS and PFS) based on the number of metastases

OS and PFS were not significantly correlated with the number of metastatic sites (Table 6). The mean OS and PFS of patients with a single metastatic site were 10.2±0.74 and 7.8±0.80 months, respectively. Patients with multiple metastatic sites exhibited comparable outcomes, with a mean OS ranging from 8.9±0.54 to 15.1±1.45 months and a mean PFS ranging from 7.7±0.67 to 11.0±1.15 months. Nevertheless, no statistically significant differences were observed between the groups (log-rank P=0.52 for OS and P=0.36 for PFS). The Kaplan-Meier survival curves (Figure 5A,5B) exhibited overlapping trajectories, indicating that the number of metastatic lesions did not independently influence survival duration.

Figure 5 Kaplan-Meier survival curve according to the number of metastasis: (A) overall survival curves (log-rank P=0.52) and (B) progression-free survival curves (log-rank P=0.36).

Univariable and multivariable Cox regression analyses

Univariable and multivariable Cox regression models were employed to identify predictors of OS and PFS (Table 7). In the univariable model, patients with lung metastases demonstrated markedly improved outcomes for OS (HR =0.27; 95% CI: 0.10–0.71; P=0.008). This association remained significant after multivariable adjustment (HR =0.31; 95% CI: 0.09–1.05; P=0.06). This data suggests that lung metastasis may be associated with a more advantageous survival profile compared to other metastatic sites. Conversely, OS was not significantly affected by chemotherapy regimen (HR =1.80, P=0.18), number of metastases (HR =0.81, P=0.72), or hepatic metastasis (HR =0.35, P=0.20).

In both the univariable (HR =0.21; 95% CI: 0.08–0.58; P=0.002) and multivariable models (HR =0.21; 95% CI: 0.06–0.71; P=0.012), lung metastasis was consistently identified as a favorable independent prognostic factor for PFS. This suggests that patients with lung metastases had a disease progression risk that was approximately 80% lower than that of patients with other metastatic sites. In contrast, the number of metastases (HR =0.73, P=0.56), chemotherapy protocol (HR =2.27, P=0.08), and hepatic metastasis (HR =0.27, P=0.11) were not significant predictors of PFS. In general, lung metastasis consistently exhibited a favorable prognostic value for both OS and PFS. Conversely, other clinicopathological variables, such as hepatic involvement, chemotherapy regimen, and metastatic burden, did not exhibit significant associations with survival outcomes.

Discussion

PC remains a significant therapeutic challenge due to its aggressive nature, late diagnosis, and poor prognosis. While FFX and GnP are the most common first-line treatments for advanced and metastatic cases, there is no global consensus on which is superior (6). Many retrospective studies have compared FFX with GnP; however, no randomized head-to-head trial can definitively direct regimen selection. Few studies consider the metastatic site as a critical prognostic factor or investigate how disease spread affects survival within treatment subgroups. The link between metastatic pattern and survival has received little attention, with most studies focusing on regimen efficacy or toxicity. Our study addresses this deficiency by demonstrating that site-specific metastases, especially pulmonary involvement, significantly impact outcomes irrespective of treatment modality. Importantly, our findings should be viewed as complementing rather than competing with previously published large Western and East Asian real-world research. While previous studies demonstrated the comparative efficacy of FFX and GnP in larger populations, the current study presents region-specific real-world data from a Middle Eastern cohort that has been significantly underrepresented in recent research. The constancy of survival trends across regions supports the external validity of current data, but our metastatic site-focused analysis provides clinically relevant context for treatment decision-making in everyday practice. In this real-world cohort study that compared first-line chemotherapy regimens in advanced PC, we found that the site of metastasis emerged as a significant prognostic factor, whereas the number of metastatic sites did not independently predict survival in our cohort.

The disparities in CR and PR rates among the groups were not statistically significant; however, the combined measures of ORR and DCR reached statistical significance, suggesting that FFX has a higher DCR in this cohort. This aligns with Klein-Brill et al., who reported improved overall response and disease control with FFX (6). Similarly, Cho et al. observed better disease control with FFX, although their study did not identify significant differences in OS or PFS (13). Additionally, the higher ORR for the FFX group in this study closely matches published data, reinforcing the applicability of these results. The notable difference illustrates the significance of disease control in selecting first-line therapy, particularly for patients with high tumor burden or aggressive disease biology. However, the finding must be interpreted cautiously, since FFX was preferentially administered to those with better performance status, indicating treatment selection bias and restricted subgroup sizes rather than definitive regimen superiority. However, treatment decisions should consider individual patient factors such as performance status, comorbidities, and potential adverse effects. Although FFX seems to work better on tumors, GnP is still a beneficial choice for patients who might not be able to handle strong chemotherapy.

The median OS and PFS in both treatment groups were 9.0 months, with no statistically significant differences detected between the two regimens. These figures align with international reports that showed no significant differences between the two regimens and support various real-world and meta-analytic studies indicating similar survival outcomes for FFX and GnP, despite differing response rates (14). Although these findings suggest broadly comparable survival outcomes between regimens, they contrast with the results of Klein-Brill et al. [2022] (6), who reported a >2-month OS advantage with FFX.

The landmark ACCORD11/PRODIGE4 trial by Conroy et al. showed that FFX significantly increased OS (11.1 vs. 6.8 months) and PFS (6.4 vs. 3.3 months) compared to gemcitabine alone, but it also led to higher toxicity, especially hematologic and gastrointestinal side effects (5). Similarly, the MPACT trial by Von Hoff et al. demonstrated that GnP provided a survival benefit over gemcitabine alone (8.5 vs. 6.7 months), although with generally lower response rates than FFX and a more tolerable side-effect profile (8). However, since there are no direct randomized comparisons between FFX and GnP, oncologists must depend on retrospective analyses, meta-analyses, and clinical judgment.

In terms of toxicity, our observation that GnP had more anemia, thrombocytopenia, and neuropathy contrasts with previous reports showing FEX had higher hematologic toxicity (5) but agrees with a report showing differences in gastrointestinal toxicity (13). These findings demonstrate how toxicity patterns can vary across different populations and treatment settings, which points to the importance of personalized supportive care. Taken together, these results reinforce current guideline recommendations that prioritize FFX for fit patients with metastatic PC while supporting the continued use of GnP in more vulnerable populations. Further studies are warranted to optimize patient selection and explore biomarkers predictive of treatment response. Metastatic site significantly influenced survival outcomes. Patients with liver metastases had negative outcomes compared with those with lymph nodes or multiple metastatic sites. This matches with Oweira, who found that patients with PC who had isolated liver metastases had worse outcomes compared to patients with isolated lung or distant nodal metastases (15). However, patients with lung metastases demonstrated markedly improved OS, indicating a more advantageous survival profile relative to other metastatic sites. Lung metastases may represent a slower-growing or less aggressive tumor biology. A previous study (16) suggests that patients with isolated lung metastases may experience fewer systemic complications compared to those with extensive liver involvement. These findings underscore the biological heterogeneity present among metastatic sites. This analysis contributes novelty by emphasizing the prognostic meaning of metastatic site in regimen comparisons, recoding site and number categories to improve the model’s strength and interpretability. On the other hand, the number of metastatic sites did not significantly affect survival outcomes, which contradicts a previous report (17). This variability could be due to a smaller sample size or regional practice patterns.

Our findings prompted clinicians to consider the metastatic site, particularly lung involvement, as a significant stratification factor in evaluating prognosis and treatment expectations. Patients with lung metastases may constitute a biologically different population exhibiting improved results. The absence of an independent influence from metastatic count indicates that the location of metastasis may be more significant than their number in prognostic evaluation.

This study encompasses its single-center, real-world design, consistent treatment period, and the incorporation of two widely utilized first-line regimens for metastatic pancreatic cancer: FFX and GnP. The thorough multivariable modeling, which considers both regimen and metastatic phenotype, supports the idea that the site of metastasis is an independent prognostic factor. However, our study has a few limitations, including the small sample size (n=60), which constrains statistical power and may fail to identify smaller effect sizes, a retrospective design with potential for unmeasured confounding. The limited sample size further reduces statistical power and increases the risk of type II errors, especially in subgroup analyses, thereby emphasizing the exploratory nature of these findings. Additionally, variability in the timing and sites of metastasis; and the employment of “mean survival times” in certain subgroup analyses when median survival could not be determined, although this work is influenced by censoring rather than design flaws. The single-center cohort from Saudi Arabia may limit the applicability to populations with diverse genetic backgrounds or healthcare systems. Subsequent research should corroborate our findings in larger, multi-center cohorts and ideally incorporate genetic profiling to investigate the underlying biology of lung-metastatic PC as a unique phenotype, as indicated by recent translational studies. Furthermore, prospective classification of patients based on metastatic sites may facilitate trial design aimed at targeting advantageous subgroups or differential therapies.

Conclusions

PC is characterized by its aggressive nature that necessitates significant challenges in early detection and treatment. This underscores the critical importance of ongoing research into novel diagnostic tools, biomarkers, and therapeutic strategies to improve patient outcomes. The novelty of our research lies in the simultaneous assessment of first-line chemotherapy regimens and metastatic phenotypes (site and number) within a regional patient population, which facilitates a more refined comprehension of prognostic determinants beyond the regimen itself. This study suggests that FFX was associated with better clinical outcomes than GnP among patients with metastatic PC. Our findings endorse the ongoing use of both regimens as effective frontline treatments, with FFX favored for patients requiring the most potent tumor response and GnP as an alternative for those less able to tolerate aggressive therapy. Further research involving larger patient cohorts and extended follow-up periods is warranted to guide clinicians in selecting the most appropriate treatment regimen.

The observed association between metastatic site and treatment response is important and merits further investigation as a potential factor in guiding treatment choices. Larger, multicenter, and biomarker-driven research is essential to fine-tune treatment approaches and enhance patient outcomes in this aggressive disease.

Acknowledgments

All authors would like to thank Dr. Wagdy M. Eldehna, Associate Professor of Pharmaceutical Chemistry at the Faculty of Pharmacy, Kafrelsheikh University, Egypt, for his invaluable help and tremendous support in the publication of this work.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-913/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-913/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-913/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-913/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study protocol was approved and reviewed by the Institutional Review Board (IRB) of the International Medical Center in Jeddah, Saudi Arabia (IRB approval No. 2024-02-236). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Informed consent for chemotherapy was obtained from all enrolled patients. The consent was signed by the patient after explaining the treatment’s side effects. Written informed consent for the publication was also obtained.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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