Assessment of polypharmacy, potentially inappropriate medications, and drug-drug interactions in older patients with cancer.

INTRODUCTION: This study aimed to determine polypharmacy, potentially inappropriate medications, and potential drug-drug interactions in elderly patients hospitalized in the oncology services of a university hospital in Turkey. METHODS: This retrospective cross-sectional study was conducted between September 2021 and September 2022 on cancer patients over 65 years old hospitalized at Suleyman Demirel University Medical Faculty Hospital in Isparta, Turkey. Potentially inappropriate medications were defined according to the 2023 Beers Criteria of the American Geriatrics Society. Potential drug-drug interactions were determined with Medscape® drug interaction checker. RESULTS: The median (min-max) of drugs used by the patients was 6 (2-15). Most of the patients (74.3%) had polypharmacy. Approximately half of the patients (51.4%) had potentially inappropriate medications. The most commonly used potentially inappropriate medications were diuretics (22.1%), metoclopramide (11.4%), antidepressant drugs (7.9%), and opioids (6.4%). The presence of comorbidities, mental, behavioral, and neurodevelopmental disorders, circulatory system diseases, and respiratory system diseases were found to be statistically significantly higher in the group with potentially inappropriate medication than in the group without potentially inappropriate medication (p < 0.05). In total, 98 patients (70%) had at least one potential drug-drug interaction. Potential drug-drug interactions were minor in 33.3%, major in 57.5%, serious in 7.74%, and contraindicated in 0.22. CONCLUSION: According to our study, polypharmacy, potentially inappropriate medications, and potential drug-drug interactions were high in elderly cancer patients. It is important to determine potential drug-drug interactions and potentially inappropriate medications in cancer patients by a multidisciplinary team, including the clinical pharmacist, to prevent possible negative consequences.

Machine learning for predicting colon cancer recurrence.

INTRODUCTION: Colorectal cancer (CRC) is a global public health concern, ranking among the most commonly diagnosed malignancies worldwide. Despite advancements in treatment modalities, the specter of CRC recurrence remains a significant challenge, demanding innovative solutions for early detection and intervention. The integration of machine learning into oncology offers a promising avenue to address this issue, providing data-driven insights and personalized care. METHODS: This retrospective study analyzed data from 396 patients who underwent surgical procedures for colon cancer (CC) between 2010 and 2021. Machine learning algorithms were employed to predict CC recurrence, with a focus on demographic, clinicopathological, and laboratory characteristics. A range of evaluation metrics, including AUC (Area Under the Receiver Operating Characteristic), accuracy, recall, precision, and F1 scores, assessed the performance of machine learning algorithms. RESULTS: Significant risk factors for CC recurrence were identified, including sex, carcinoembryonic antigen (CEA) levels, tumor location, depth, lymphatic and venous invasion, and lymph node involvement. The CatBoost Classifier demonstrated exceptional performance, achieving an AUC of 0.92 and an accuracy of 88 % on the test dataset. Feature importance analysis highlighted the significance of CEA levels, albumin levels, N stage, weight, platelet count, height, neutrophil count, lymphocyte count, and gender in determining recurrence risk. DISCUSSION: The integration of machine learning into healthcare, exemplified by this study's findings, offers a pathway to personalized patient risk stratification and enhanced clinical decision-making. Early identification of individuals at risk of CC recurrence holds the potential for more effective therapeutic interventions and improved patient outcomes. CONCLUSION: Machine learning has the potential to revolutionize our approach to CC recurrence prediction, emphasizing the synergy between medical expertise and cutting-edge technology in the fight against cancer. This study represents a vital step toward precision medicine in CC management, showcasing the transformative power of data-driven insights in oncology.

Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

Prognostic value of computed tomography associated body composition measurement changes in metastatic colorectal cancer patients.

BACKGROUND: Sarcopenia is associated with poor prognosis in metastatic colorectal cancer (mCRC) patients. PURPOSE: To investigate the prognostic value of body composition measurement changes measured by computed tomography (CT) in mCRC patients. MATERIAL AND METHODS: The abdominal skeletal muscle density (SMD) and skeletal muscle (SMI) indices, as well as the visceral (VATI) and subcutaneous fat tissue (SATI) indices, were calculated by automatic segmentation method on the abdominal CT images obtained before (n = 71) and after chemotherapy (n = 52). Skeletal muscle gauge (SMG = SMD × SMI) was calculated. We calculated the percentage change of body composition measurements with respect to the first measurements. The cutoff value for the change in SMG was calculated by receiver operating characteristic analysis. Kaplan-Meier and Cox regression analyses were performed to calculate the prognostic value of age, gender, tumor location, metastasis site and carcinoembriogenic antigen (CEA) elevation, hypoalbuminemia, body mass index classification, presence of sarcopenia and SMG changes in terms of overall survival. RESULTS: There was a significant association between SMG change and mortality (P = 0.037). According to survival analyses, highly decreased SMG, hypoalbuminemia and CEA variables of the patients were the significant factors (P < 0.001, P = 0.015 and P = 0.019, respectively). According to multivariate regression analysis, hypoalbuminemia (P = 0.004, hazard ratio = 3.60) and highly decreased SMG (P < 0.001, hazard ratio = 14.98) were found to be significant prognostic factors together. CONCLUSION: In mCRC patients, hypoalbuminemia and highly decreased SMG are significant prognostic factors for overall survival. Therefore, we suggest that the change in SMG calculated in follow-up images should also be evaluated in the prognosis estimation of this patient group.

Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Potential drug-drug interactions in patients with non-small cell lung cancer at a university hospital in Turkey.

BACKGROUND: The aim of this study was to determine the drug profile of patients with non-small cell lung cancer (NSCLC) and to identify potential drug-drug interactions (PDDIs) during hospitalization. In particular, PDDIs in categories X and D were determined. METHODS: This retrospective cross-sectional study was conducted in the oncology services of a university hospital between 2018 and 2021. PDDIs were evaluated using Lexicomp Drug Interactions® software included in UpToDate®. RESULTS: A total of 199 patients were included in the study. Polypharmacy was present in 92.5% of the patients and the median (min-max) number of drugs used was 8 (2-16). 32% of the patients had D and X PDDIs. A total of 16 PDDIs at risk grade X were found in 15 (7.5%) patients. A total of 81 PDDIs of risk grade D were found in 54 (27.1%) patients and a total of 276 PDDIs of risk grade C were identified in 97 (48.7%) patients. Anticancer drugs (p = 0.008), opioids (p = 0.046), steroids (p = 0.003), 5-HT3 receptor antagonists (p = 0.012), aprepitant (p = 0.025) and antihistamines (p < 0.001) were statistically more frequent among patients with PDDIs than among those without. CONCLUSION: The results of our study indicated that polypharmacy and PDDIs are common in hospitalized patients with NSCLC cancer. The monitoring of medications is critical for maximizing therapeutic effects and minimizing side effects related to PDDIs. As a part of multidisciplinary team, clinical pharmacists can contribute significantly to preventing, detecting and managing PDDIs.

Prognostic value of claudin 18.2 expression in gastric adenocarcinoma.

BACKGROUND: Claudin 18.2 (CLDN18.2) is a cell surface protein expressed by gastric cancer cells. The monoclonal antibody zolbetuximab binds CLDN18.2-positive cancer cells and causes cancer cell death. A few studies researched the prognostic effect of CLDN18.2 expression in metastatic gastric adenocarcinoma. AIM: To identify the prognostic value of CLDN18.2 expression in patients with metastatic gastric adenocarcinoma. METHODS: This study was conducted with 65 patients over the age of 18 who were diagnosed with metastatic gastric adenocarcinoma. We investigated the effect of CLDN18.2 expression on clinicopathological characteristics (age, sex, histological grade, Lauren classification, family history, metastatic site, HER2 expression) and prognosis for patients with metastatic gastric adenocarcinoma. RESULTS: CLDN18.2 expression was positive in 73.8% (48) of the patients. During the median 17.7-mo follow-up period, 89.2% (58) of the patients died. Median progression-free survival and overall survival (OS) were 6 mo (95% confidence interval: 1.6-10.4) and 12 mo (95% confidence interval: 7.5-16.5). There was no statistically significant correlation between CLDN18.2 expression and clinicopathological characteristics of the patients. In univariate and multivariate Cox regression analysis, there was no correlation between clinicopathological characteristics of patients and progression-free survival or OS. CONCLUSION: CLDN18.2 expression was quite high in patients with gastric adenocarcinoma, identifying the proportion of the patients in whom zolbetuximab would be efficacious. There is no statistically significant correlation with clinicopathological characteristics and OS. CLDN18.2 is not a prognostic marker in patients with gastric adenocarcinoma, although it is predictive.

A Novel Prognostic Index for Metastatic Colon Cancer: The Prognostic Immune Nutritional Index.

Objective Systemic inflammation and nutrition are associated with survival outcomes in metastatic colon cancer (mCC) patients. A new and strong prognostic marker named the Prognostic Immune Nutritional Index (PINI) was proposed as the best marker for outcomes in metastatic colon cancer patients. This study aimed to evaluate the prognostic significance of PINI in mCC patients. Methods The data of 190 patients who were admitted to our center and diagnosed with mCC between 2010 and 2020 abiding by our inclusion criteria were reviewed retrospectively. Receiver operating characteristic (ROC) analysis was used to identify the optimum cutoff value of PINI for overall survival (OS). Results The mean age of the participants was 62.64±11.99 years. The median follow-up time was 25.81 months. According to PINI, the median OS in patients who had PINI<3 was 22.70 months (95% confidence interval (CI): 16.05-29.35), and the median OS in patients who had PINI≥3 was 38.83 months (95% CI: 26.98-37.01) (p<0.001). PINI score lower than 3 was an independent prognostic indicator in multivariate analysis. Conclusions PINI was discovered to be an independent prognostic factor in metastatic colorectal cancer. We believe that PINI, which can be calculated using a simple formula, will provide clinicians with important clues when deciding on individual treatment.

The role of claudin 18.2 and HER-2 in pancreatic cancer outcomes.

To examine the prognostic value of claudin 18.2 (CLDN18.2) and human epidermal growth factor receptor-2 (HER-2) expression in patients with resected pancreatic ductal adenocarcinoma (PDAC). This study enrolled patients who underwent surgery and were diagnosed with PDAC at Suleyman Demirel University Hospital, Turkey between 2015 and 2019. Sixty-eight patients with resected PDAC treated at a medical oncology clinic were assessed. All patients were over the age of 18 years, underwent follow-up and treatment in our unit, and had pathology slides that we could access. Clinicopathological data were obtained from medical files, including the patients' age, sex, pathological parameters, and clinical stage according to the Eighth International Union against Cancer/American Joint Committee on Cancer. Patient survival and the period from the date of diagnosis to death were assessed in the follow-up data. There was no statistically significant difference between CLDN18.2 and HER-2 expression scores for samples and patient clinicopathological characteristics. No HER-2 expression scores of ≥2 were found in the samples. Only 25% (n = 17) of the samples had HER-2 expression scores of +1. CLDN18.2 expression was detected in 54.4% (n = 37) of the patient samples. CLDN18.2 expression scores were +1 in 30.8% (n = 21) of the patient samples, +2 in 16.2% (n = 11), and +3 in 7.4% (n = 5). When CLDN18.2 and HER-2 expression were compared, a statistically significant difference and moderate positive correlation were observed. No significant relationship between HER-2 expression and survival was observed in the survival analysis of PDAC patients; however, high CLDN18.2 expression was related to longer overall survival. Our study is the third to research CLDN18.2 expression in PDAC. HER-2 expression is low and CLDN18.2 expression is high in patients with PDAC. HER-2 expression is not related to overall survival but CLDN18.2 is related and may be used as a prognostic marker in patients with PDAC.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.