Cancer Research Articles

Survey of healthcare professionals’ awareness of appearance care for Japanese cancer patients and their institutions’ appearance care systems: report from the Japan Society of Clinical Oncology

Survey of healthcare professionals’ awareness of appearance care for Japanese cancer patients and their institutions’ appearance care systems: report from the Japan Society of Clinical Oncology

Autoimmune pancreatitis, pancreatic and extrapancreatic cancer (AIPPEAR): a multicentre, retrospective study protocol

IntroductionAutoimmune pancreatitis (AIP) mainly manifests in two distinct forms with different clinical, serological and prognostic characteristics. Previous studies indicated a higher risk of malignancy in AIP patients compared with the...

Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.

Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur. Therefore, to expand the repertoire of ubiquitin ligases that can be utilized in PROTACs, we aimed to develop a versatile system to identify suitable novel ubiquitin ligases for PROTAC-mediated protein degradation using existing PROTACs. Chimeric ubiquitin ligases are constructed by fusing VHL with the ubiquitin ligase of interest that is stably expressed in cells. An existing PROTAC that binds to VHL was added to the cells, and the POI degradation activity was evaluated. In this study, we showed that epidermal growth factor receptor can be degraded by an existing PROTAC utilizing a chimeric ubiquitin ligase that fuses VHL and endoplasmic reticulum-localized ubiquitin ligase, HRD1. These results demonstrate that this novel approach can be used to identify suitable ubiquitin ligases for PROTAC-mediated degradation using existing PROTACs. Expanding the repertoire of ubiquitin ligases that can be utilized for PROTAC by using this versatile system is expected to enable the development of more effective and specific PROTACs for cancer and other diseases.

Machine learning-based identification of co-expressed genes in prostate cancer and CRPC and construction of prognostic models

The objective of this study was to employ machine learning to identify shared differentially expressed genes (DEGs) in prostate cancer (PCa) initiation and castration resistance, aiming to establish a robust prognostic model and enhance understanding of patient prognosis for personalized treatment strategies. mRNA transcriptome data associated with Castration-Resistant Prostate Cancer (CRPC) were obtained from the GEO database. Differential expression analysis was conducted using the limma R package to compare normal prostate samples with PCa samples, and PCa samples with CRPC samples. Next, we applied LASSO regression, univariate, and multivariate COX regression analyses to pinpoint genes linked to prognosis and build prognostic models. Validation was performed using the TCGA_PRAD dataset to confirm expression differences of hub genes and explore their correlation with clinical variables and prognostic significance. We successfully established a prostate cancer risk prognostic model containing seven genes (KIF4A, UBE2C, FAM72D, CCDC78, HOXD9, LIX1 and SLC5A8) and verified its accuracy on an independent data set. The results of calibration curve and decision curve show that the model has potential clinical application value. The nomogram can accurately predict the prognosis of patients. Additionally, elevated expression of KIF4A, UBE2C, and FAM72D, or reduced expression of LIX1, correlated with advanced pathological T and N stages, clinical T stage, prostate-specific antigen (PSA) level, age at diagnosis, Gleason score, and shorter progression-free interval (PFI) (P < 0.05). By integrating bioinformatics analysis and clinical data, we not only established a reliable prognostic model for prostate cancer but also identified key genes pivotal in disease progression and treatment resistance. These findings provide novel insights and methodologies for assessing prognosis and tailoring treatment strategies for prostate cancer patients.

Anxiety and depression in cancer patients and survivors in the context of restrictions in contact and oncological care during the COVID-19 pandemic.

Treatment modifications and contact restrictions were common during the COVID-19 pandemic and can be stressors for mental health. There is a lack of studies assessing pandemic-related risk factors for anxiety and depression of cancer patients and survivors systematically in multifactorial models. A total of 2391 participants, mean age 65.5 years, ≤5 years post-diagnosis of either lung, prostate, breast, colorectal cancer, or leukemia/lymphoma, were recruited in 2021 via the Baden-Württemberg Cancer Registry, Germany. Sociodemographic information, pandemic-related treatment modifications, contact restrictions, and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were assessed via self-administered questionnaire. Clinical information (diagnosis, stage, and treatment information) was obtained from the cancer registry. Overall, 22% of participants reported oncological care modifications due to COVID-19, mostly in follow-up care and rehabilitation. Modifications of active cancer treatment were reported by 5.8%. Among those, 50.5% had subclinical anxiety and 55.4% subclinical depression (vs. 37.4% and 45.4%, respectively, for unchanged active treatment). Age <60 years, female sex, lung cancer, low income, and contact restrictions to peer support groups or physicians were identified as independent risk factors for anxiety. Risk factors for depression were lung cancer (both sexes), leukemia/lymphoma (females), recurrence or palliative treatment, living alone, low income, and contact restrictions to relatives, physicians, or caregivers. The study demonstrates that changes in active cancer treatment and contact restrictions are associated with impaired mental well-being. The psychological consequences of treatment changes and the importance for cancer patients to maintain regular contact with their physicians should be considered in future responses to threats to public health.

Early circulating tumor DNA changes predict outcomes in head and neck cancer patients under re-radiotherapy.

Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.

Learning and actioning general principles of cancer cell drug sensitivity

High-throughput screening of drug sensitivity of cancer cell lines (CCLs) holds the potential to unlock anti-tumor therapies. In this study, we leverage such datasets to predict drug response using cell line transcriptomics, focusing on models’ interpretability and deployment on patients’ data. We use large language models (LLMs) to match drug to mechanisms of action (MOA)-related pathways. Genes crucial for prediction are enriched in drug-MOAs, suggesting that our models learn the molecular determinants of response. Furthermore, by using only LLM-curated, MOA-genes, we enhance the predictive accuracy of our models. To enhance translatability, we align RNAseq data from CCLs, used for training, to those from patient samples, used for inference. We validated our approach on TCGA samples, where patients’ best scoring drugs match those prescribed for their cancer type. We further predict and experimentally validate effective drugs for the patients of two highly lethal solid tumors, i.e., pancreatic cancer and glioblastoma.

ASO Author Reflections: Reshaping Tumor Size through Insights from Pancreatic Cancer Imaging and Pathology.

ASO Author Reflections: Reshaping Tumor Size through Insights from Pancreatic Cancer Imaging and Pathology.

Effect of neoadjuvant chemotherapy on CD14 + CD16 + monocytes and soluble CD163 in Egyptian breast cancer patients

Neoadjuvant chemotherapy (NACT) influences the anticancer response by favourably altering the immune microenvironment. However, the effects of NACT on peripheral monocytes and their prognostic contribution to the NACT response have not yet been clarified. We aimed to evaluate the potential therapeutic responses and possible predictive value of double-positive (CD14 + CD16 +) monocytes and soluble CD163 (sCD163) in Egyptian breast cancer patients. Blood samples were obtained before and after neoadjuvant therapy from 30 patients with invasive breast cancer, and the expression of CD14 and CD16 was assessed via flow cytometry. The patients’ sCD163 levels were also determined in both the serum and culture supernatant using enzyme-linked immunosorbent assay (ELISA). The results revealed that NACT was associated with a significant decrease in double-positive monocytes and sCD163 levels. In addition, both double-positive monocytes and serum sCD163 were significantly associated with a partial clinical response. Double-positive monocytes and serum sCD163 levels may be related to therapeutic response, suggesting their possible predictive value in breast cancer patients receiving NACT.

Predictive value of perioperative fasting blood glucose for post pancreatectomy diabetes mellitus in pancreatic ductal carcinoma patients

BackgroundTo explore the risk factors of post pancreatectomy diabetes mellitus (PPTDM)in pancreatic ductal carcinoma (PDAC) patients and the value of perioperative fasting blood glucose (FBG) level expression on the long-term survival after surgery.Materials and methodsBetween December 2015 and December 2019, a cohort of 509 patients diagnosed with PDAC and undergoing resection at our hospital was analyzed. They were stratified into two groups, Control group (Control) and study group (PPTDM), depending on the onset of postoperative diabetes mellitus. We analyzed the survival rates at 6 months, 12 months and 24 months post-operation in the two groups. We use univariate and logostic multivariate regressions to analyze the risk factors for PPTDM. ROC curve analysis was conducted to assess the diagnostic significance of perioperative FBG levels regarding patients’ long-term survival rates. The Kaplan-Meier method was employed to assess the impact of both preoperative and postoperative FBG levels on the survival rates within 24 months for each patient group.ResultsThe comparison of general clinical data between the two groups shows marginal differences without statistical significance(P > 0.05); Patients in PPTDM group had significantly higher BMI, preoperative jaundice proportion, larger tumor diameter, higher TNM stage and higher proportion of distal pancreatectomy (DP), with P values of 0.023, 0.010, 0.040, 0.012 and 0.005, respectively. The levels of preoperative FBG and postoperative FBG in PPTDM patients exhibited statistically significant elevation compared to the control group (P < 0.05). There were no significant differences in surgery-related indicators between the two groups in operative time, number of dissected positive lymph nodes, total number of dissected lymph nodes, intraoperative blood loss and other related data (P > 0.05). Hospitalization duration of PPTDM patients was longer than control group (P = 0.047). PPTDM group had significantly higher expression concentrations of BUN, Cr, TG, LDL and Apo-B factors (P = 0.023, 0.024, 0.013, 0.045 and 0.017). 17 patients (5.03%) died in the PPTDM group and 4 patients (2.35%) in control group which had significantly difference (P = 0.020). In univariate and logostic multivariate regression analysis indicated tumor size, jaundice, BUN, Cr, TG, LDL, Apo-B concentrations and DP approach were significantly correlated to the risk for PPTDM (P < 0.05). ROC curve analysis results showed combining of preoperative and postoperation FBG showed the highest diagnostic efficacy, followed by postoperation FBG and preoperative FBG. The AUC areas of the three groups were 0.745, 0.623 and 0.588, respectively, and the critical values of the three groups were 9.81/9.95 mmol/L, 10.18 mmol/L and 10.23 mmol/L, respectively, with statistical significance (P < 0.05). Results were considered statistically significant if the p-value was less than 0.05.ConclusionPPTDM stands as a significant postoperative complication following pancreatic cancer surgery, characterized by a high incidence and severity. Several risk factors have garnered considerable attention among clinical surgeon. PPTDM may be an influential factor in postoperative prognosis of pancreatic cancer. The expression levels of preoperative and postoperative blood glucose hold diagnostic value for the long-term prognosis of pancreatic cancer patients. Early regulation and intervention by surgeons concerning perioperative FBG could potentially mitigate the risk of PPTDM.

Distinct clinicopathological features and treatment differences in breast cancer patients of young age

The incidence of breast cancer in young women (aged under 40) is on the rise and is associated with more aggressive tumor characteristics and lower survival rates. Breast cancer is most frequently diagnosed in the sixth decade, and most research presents results based on data from older patients. By using large-scale clinico-pathologic and transcriptomic data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1932), we aimed to explore age-related differences in treatment, tumor characteristics, and gene expression signatures. Young patients presented more aggressive clinico-pathologic features such as higher histological grade, more frequent lymph node metastasis involvement, and estrogen receptor negativity. Accordingly, age below 40 years was associated with lower mRNA expression of the estrogen- and progesterone receptors, encoded by ESR1 and PGR, a higher proportion of the basal-like subtype, and increased transcription patterns reflecting stemness. Young breast cancer patients showed reduced survival, also within the basal-like subtype. We observed age-related differences in treatment, with more patients receiving chemotherapy among the young. Our results confirm a more challenging disease in young patients with breast cancer despite the more abundant use of chemotherapy. This argues for increased attention to young patients in current management and future research in breast cancer.

Potential use of DNA methylation in cervical swabs for early ovarian cancer diagnosis

IntroductionEarly diagnosis of ovarian cancer, using cost-effective and non-invasive methods remains an unmet medical need, largely due to unspecific symptoms of the disease.ObjectiveOur goal was to identify differentially methylated CpG loci between cervical swabs obtained from patients diagnosed with benign ovarian disease and with malignant pelvic mass.MethodologyUsing Infinium EPICv2 array, we interrogated methylation profiles of 77 cervical swabs. The study cohort was then divided into a training and testing set to develop a diagnostic signature. We applied several strategies to pinpoint CpG sites able to differentiate cervical swabs obtained from ovarian cancer patients and patients with benign ovarian disease.Results and conclusionsNone of the statistical methods applied identified CpG loci capable of diagnosing ovarian cancer with sufficient specificity and sensitivity. We conclude that methylation differences observed do not adequately distinguish between benign and malignant ovarian disease. The variations attributable to clinical conditions are likely obscured by the differences in cell composition, which is the primary source of sample heterogeneity. Therefore, we suggest that diagnostic tools should not rely on local methylation profile of the cervix but rather focus on detecting cancer-specific sequences transferred from the tumor site and present in cervical swabs.Non-technical summaryOvarian cancer is difficult to detect early, and we aimed to explore whether DNA methylation in cervical swabs could serve as a diagnostic tool. However, our study found that methylation patterns in these samples do not reliably distinguish between benign and malignant conditions, likely due to variations in cell composition. We recommend future research focus on detecting tumor-specific DNA sequences in cervical swabs instead.

Novel FAP-Targeted Heptamethine Cyanines for NIRF Imaging Applications.

Fibroblast activation protein (FAP) is a pan-cancer target that is useful for imaging, ideally all epithelial cancers. This work aimed to develop, characterize, and validate two novel FAP-targeted probes for optical imaging, both in vitro and in vivo. IRDye800CW and FNIRTag heptamethine cyanines were conjugated to the NH precursor of the well-known FAP inhibitor FAPI-46, which is widely employed in nuclear medicine. In addition to synthesis, the dyes were characterized in terms of physicochemical properties, biodistribution, and imaging performances in a breast cancer tumor model. FAPI-FNIRTag showed a stronger fluorescence and higher photostability compared to FAPI-IRDye800CW. Notably, both compounds exhibited strong tumor accumulation in TUBO breast cancer-bearing mice 24 h postadministration, suggesting potential for further investigation as fluorescence-guided surgery (FGS) agents.

Validation of the Skindex-16 questionnaire for assessing patient-reported outcomes in radiation dermatitis among breast cancer patients.

Radiation dermatitis (RD) is often experienced by cancer patients undergoing radiation therapy (RT) and can negatively impact the quality of life of patients. The Skindex-16 questionnaire is an instrument that measures the impact of skin conditions on patient quality of life. The Skindex-16 has been validated for use in assessing many benign conditions, however it has not yet been validated for the assessment of patient-reported outcomes (PROs) for patients experiencing RD. A group of 42 breast cancer patients enrolled in a StrataXRT study for RD were analyzed. Increases in Skindex-16 scores indicate worsening symptoms. To validate the Skindex-16, scores were compared at baseline, 2weeks, and 3months post-RT. Skindex-16 scores were also compared to scores from the Common Terminology Criteria of Adverse Events (CTCAE) for RD and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) using various statistical analyses at baseline, 2weeks, and 3months post-RT. Skindex-16 scores were found to be low at baseline and 3months post-RT but peaked at 2weeks post-RT. Significant worsening scores from baseline to 2weeks post-RT were found in a longitudinal assessment of Skindex-16 items for several items on the patient portion of the RISRAS, but only two items on the healthcare professional RISRAS component. Skindex-16 scores showed no significant relationship to CTCAE scores. This validation of the Skindex-16 questionnaire indicates that it is reliable to be used for the assessment of PROs for cancer patients experiencing RD. However, the PROs assessed by Skindex-16 do not correlate with clinician-reported outcomes.

Pneumocystis jirovecii Pneumonia in Cancer Patients, a Lethal Yet Fully Preventable Disease: Insights From a Tertiary Cancer Center in East India.

Pneumocystis jirovecii pneumonia (PCP) is an unrecognized infection in non-HIV patients, particularly those with solid and hematologic malignancies. These patients experience higher mortality rates. This study aims to describe the incidence, initial characteristics, management, and outcomes of PCP at a tertiary cancer care center. This retrospective observational study included all patients who underwent P. jirovecii PCR testing at our center from January 2019 to January 2022. PCP was diagnosed in PCR-positive patients. Data on demographics, treatment, and outcomes were extracted from medical records. The primary outcomes were ICU admission and 21-day mortality. Statistical analysis compared PCR-positive and PCR-negative patients, with a specific focus on lung cancer patients, and analyzed determinants of 21-day mortality in PCP patients. Of the 345 patients suspected of PCP, 54 (15.7%) were diagnosed with PCP. PCP patients were generally older. None of the PCP patients were on prophylaxis, compared to 14.8% of PCR-negative patients. In lung cancer patients, age and radiotherapy within the past year were significantly associated with a PCP diagnosis. The 21-day mortality rate among PCP patients was 35.4%. Independent risk factors for mortality included age and hematologic malignancy, while recent chemotherapy and higher neutrophil counts were associated with lower mortality. PCP is associated with the highest mortality in patients with hematologic malignancies and lung cancer. The findings underscore the importance and efficacy of prophylaxis in at-risk groups and should raise awareness for the diagnosis of PCP in overlooked populations, such as older cancer patients and those undergoing radiotherapy.

Psychological Distress and Sexual Dysfunction in Cancer Patients: Need for Psychological Intervention

Psychological Distress and Sexual Dysfunction in Cancer Patients: Need for Psychological Intervention

The burden of COVID-19 death for different cancer types: a large population-based study.

Viral mutations and immune dysfunction still lead to recurrent infections of COVID-19 in cancer patients. Our aim in this study was to explore the differences in cumulative risk of COVID-19 death from different cancer types and characterise clinical and demographic factors associated with COVID-19 death. We conducted a population-based study using the National Cancer Database, which included all cancer types. We calculated age-standardised mortality, cancer mortality, and COVID-19 mortality. Further, we employed a multivariate competing risk analysis to calculate the cumulative risk of COVID-19 death in different cancer types. 5.3% of cancer patients suffered from COVID-19 death. The highest COVID-19 mortality was in chronic lymphocytic leukaemia, while lung and bronchus cancer exhibited lower risk. Notably, years from cancer diagnosis independently predict COVID-19 death. The hazard ratios (HR) in different types of cancers were as follows: lung and bronchus cancer HR = 1.29 (95% confidence interval (CI) = 1.20-1.40, P < 0.001), colon and rectum cancer HR = 1.22 (95% CI = 1.16-1.29, P < 0.001), urinary bladder cancer HR = 1.22 (95% CI = 1.15-1.30, P < 0.001), non-Hodgkin lymphoma HR = 1.17 (95% CI = 1.11-1.23, P < 0.001), kidney cancer HR = 1.15 (95% CI = 1.06-1.24, P < 0.001), and breast cancer HR = 1.11 (95% CI = 1.06-1.16, P < 0.001). Radiotherapy, chemotherapy, and surgical resection did not significantly correlate with COVID-19 death. We revealed the burden of COVID-19 death across different cancer types. COVID-19 mortality was highest in chronic lymphocytic leukaemia and prostate cancer, while patients with lung and bronchus cancer had a lower risk. Years from diagnosis independently predict COVID-19 death. Based on the results, we support more prompt risk assessment and treatment for various types of cancer.

Distinctive circulating microbial metagenomic signatures in the plasma of patients with lung cancer and their potential value as molecular biomarkers

Lung cancer (LC) remains the leading cause of cancer death globally. Recent reports have suggested that circulating microbial nucleic acids have potential as promising biomarkers for cancer liquid biopsies. However, circulating microbial profiles and their potential clinical value in LC patients remained unexplored. In this study, plasma samples from 76 LC patients, 9 liver cancer patients, 11 pancreatic cancer patients, and 53 healthy controls (HCs) were collected and underwent metagenomic analyses by whole genome sequencing. The composition and relative abundance of the microbial profiles were significantly different between the LC patients and HCs. A distinct plasma-based microbial profile was observed in LC patients. By differential analysis using MaAslin, 40 significant species between LC patients and HCs were identified. Five species were selected as optimal circulating microbial biomarkers for LC. The constructed classifier based on these five species showed an AUC of 0.9592, 0.9131, and 0.8077 in the discovery, validation, and additional validation cohorts, respectively. Furthermore, metagenomic profiles of 25 lung tumor tissue and plasma paired samples were analyzed and compared. The microbial diversity was significantly increased in plasma compared with the tumor tissue. Among the 13 shared core microbial species, 10 had no difference between the tumor tissue and paired plasma. In conclusion, circulating microbial nucleic acids in the plasma have potential as biomarkers for LC liquid biopsies. The microbiome in the tumor tissue was one of the possible sources of circulating microbial nucleic acids.

Honokiol-Magnolol-Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti-PD-1 Immunotherapy in Colorectal Cancer by Triggering GSDME-Dependent Pyroptosis.

Significant progress is made in the treatment of metastatic colorectal cancer (mCRC) patients, however, therapeutic options remain limited for patients with mCRC. In recent years, traditional Chinese medicine (TCM) has gained significant attention. Among these, Huangqin Houpo decoction has demonstrated efficacy in mCRC treatment. Despite its promise, the active ingredients and mechanisms underlying its anticancer effects remain unclear. Using integrative pharmacological approaches, six compounds are identified as the primary active ingredients in Huangqin Houpo decoction. Among them, honokiol (H), magnolol (M), and baicalin (B) are found to exhibit a synergistic anticancer effect on CRC. The HMB combination significantly outperforms mono- or bi-agent treatments in reducing tumor growth. Furthermore, the anticancer efficacy of the HMB combination surpasses that of medium- and high-dose Huangqin Houpo decoction and the FOLFOX regimen. Notably, HMB is comparable in efficacy to the FOLFOIRI regimen. Most importantly, HMB is shown to enhance the sensitivity of CRC cells to anti-PD-1 immunotherapy in vivo. Mechanistic studies reveal that the HMB combination exerts its synergistic anticancer effects and enhances anti-PD-1 immunotherapy by inducing GSDME-dependent pyroptosis. Our study will hopefully provide a potential therapeutic strategy for mCRC patients in the future.

PPIs effect in EGFR-TKI-associated interstitial lung diseases in patients with non-small cell lung cancer

BackgroundPrevious studies suggest a potential link between interstitial lung diseases (ILD) and EGFR-TKI use, with proton pump inhibitors (PPIs) possibly affecting EGFR-TKI-associated ILD differently. Our objective is to use the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore the potential link between ILD and the combination of PPIs and EGFR-TKI.MethodsA retrospective examination of adverse event reports in the FAERS database spanning from the initial quarter of 2016 and the fourth quarter of 2023 was conducted. Disproportionality analysis, generalized linear models, and adjusted multivariable logistic regression were employed to assess the occurrence of EGFR-TKI-associated ILD in non-small cell lung cancer (NSCLC) patients receiving PPIs compared to those not receiving PPIs.ResultsThe reporting odds ratio (ROR) for PPIs combined with EGFR-TKIs demonstrated statistical significance (ROR 1.84, 95% CI 1.54–2.19). Significant increases were noted in both additive and multiplicative models (p < 0.001), as well as in the adjusted odds ratios derived from multivariate analysis (1.77, 95% CI 1.42–2.19, p < 0.001). Stratified analysis reveals that the combination of lansoprazole or esomeprazole and EGFR-TKI was linked to an elevated risk of ILD, with a ROR of 2.37 (95% CI 1.84–3.04) and 2.90 (95% CI 2.11–3.98), respectively, surpassing the risk associated with either medication used independently. Similarly, the ROR for osimertinib or gefitinib combined with PPIs stands at 2.20 (95% CI 1.83–2.66) and 2.33 (1.35–4.02), respectively, exceeding the risk when either drug is used alone.ConclusionsOur study uncovered a heightened risk of ILD in NSCLC patients receiving certain EGFR-TKI in conjunction with specific PPIs, as opposed to EGFR-TKI monotherapy. Subsequent analysis indicates that different PPIs may elicit divergent effects on EGFR-TKI-associated ILD, with different EGFR-TKIs exhibiting distinct responses to combinations with different PPIs. Therefore, NSCLC patients undergoing such treatments should be meticulously monitored for ILD.