Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial.

BACKGROUND: We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC). METHODS: Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported. CONCLUSIONS: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626). CLINICAL TRIAL REGISTRATION: NCT03694522.

Cardiac safety of ribociclib evaluated with 24-hour rhythm Holter electrocardiogram.

OBJECTIVE: We aimed to evaluate cardiac safety profile of ribociclib with 24-h rhythm Holter ECG. MATERIAL AND METHOD: Forty-two female metastatic breast cancer patients were included in the study. Rhythm Holter ECG was performed before starting treatment with ribociclib and after 3 months of the treatment initiation. RESULTS: The mean age of the patients was 56.36 ± 12.73. 52.4% (n = 22) of the patients were using ribociclib in combination with fulvestrant and 47.6% (n = 20) with aromatase inhibitors. None of the patients developed cardiotoxicity. When the rhythm Holter results before and in third month of the treatment were compared, there was no statistically significant difference. CONCLUSION: This is the first study evaluating effects of ribociclib treatment on cardiac rhythm with Holter ECG. The findings suggested ribociclib has a low risk of causing early cardiotoxicity.

Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

The correlation between skeletal muscle index and anxiety in patients with lung cancer on the first day of chemotherapy.

Aim: To evaluate the relationship between anxiety and skeletal muscle index (SMI) levels in lung cancer patients on the first day of chemotherapy. Materials & methods: This cross-sectional study included 108 patients. We analyzed patient characteristics, SMI levels, pain status and predicted anxiety factors. Results: Anxiety was detected in 61% of patients. SMI levels were significantly lower in the high anxiety group than the low anxiety group (p < 0.001). A significant correlation was observed between anxiety and SMI levels (r = -0.292; p = 0.002). Anxiety levels were significantly correlated with trait anxiety (r = 0.618; p < 0.001) and visual analog scale-pain (r = 0.364; p < 0.001). SMI (odds ratio: 0.94), trait anxiety (odds ratio: 1.12) and visual analog scale pain (odds ratio: 1.28) were independent risk factors for anxiety after adjusting for sex, stage and Eastern Cooperative Oncology Group performance status. Conclusion: Our study highlighted that higher anxiety scores were significantly correlated with lower SMI levels. We found that SMI, pain and trait anxiety were independent risk factors for anxiety.

Comparison of different decision support software programs in perspective of potential drug-drug interactions in the oncology clinic.

INTRODUCTION: One of the most intriguing situations for healthcare providers is cancer therapy. Drug-drug interactions (DDIs) account for 20-30% of all adverse effects. Cancer patients are more likely to have potential-DDIs since they are taking other drugs with anticancer treatments to prevent the side effects of chemotherapeutic agents. The purpose of this research is to compare various decision support software (CDSS) programs in terms of potential DDIs. METHODS: A cross-sectional study was carried out. A clinical pharmacist assessed the treatment regimens of 231 cancer patients. pDDIs were evaluated using three sources: Lexicomp®, Medscape®, and Micromedex®. The ethical approval was given in November 2017 with decision number 21/286. RESULTS: A total of 231 participants who were receiving therapy and had a median age of 61.5 ± 9.18 years were assessed. Almost half of the patients (49%) were female, and 155 had at least one comorbidity in addition to cancer. Medscape had a substantial pDDI ratio of 7.09%, Micromedex had a ratio of 11.15%, and Lexicomp had a ratio of 19.50%. The total number of pDDIs for major/X/contraindicated were 363-2716 (1.56-11.7 pDDI/patient) for Medscape®, 60-1723 (0.26-7.4 pDDI/patient) for Micromedex, and 145-984 (0.62-2.24 pDDI/patient) for Lexicomp®. One of the most common pDDI found was diclofenac and dexamethasone. Interactions between escitalopram and granisetron were also common, and different CDSSs made different recommendations. CONCLUSIONS: In this study, significant disparities in the quantity and severity of CDSS across distinct CDSS were discovered. One of the major finding of our study was suboptimal prescribing. To address this issue, regulatory organizations should establish and verify validation and reporting mechanisms.

The risk of malnutrition and its clinical implications in older patients with cancer.

AIM: Malnutrition is a common geriatric syndrome with multiple negative outcomes including mortality. However, there is a scarcity of literature that focuses on the relationship between malnutrition risk and its clinical implications on geriatric syndromes and mortality among cancer patients. The aim of this study is to determine the clinical importance of malnutrition risk in geriatric oncology practice. METHOD: 180 patients with cancer who were ≥ 65 years were included in the study. All patients were questioned in terms of geriatric syndromes, including polypharmacy, frailty, probable sarcopenia, fall risk, dynapenia, depression, cognitive impairment, insomnia, and excessive daytime sleepiness. Mini Nutritional Assessment scores > 23.5 and 17-23.5 were categorized as well-nourished and malnutrition risk, respectively. RESULTS: Of the 180 patients (mean age 73.0 ± 5.6 years, female: 50%), the prevalence of malnutrition risk was 28.9%. There was no statistically significant difference between the groups in terms of age, gender, education, marital status, body mass index, and comorbidities except for chronic obstructive pulmonary disease (p > 0.05). After adjustment for age, sex, and body mass index; polypharmacy (odds ratio [OR]: 3.17; 95% confidence interval [CI], 1.48-6.81), reduced calf circumference (OR: 3.72; 95% CI, 1.22-11.38), fall risk (OR: 2.72; 95% CI, 1.03-7.23), depression (OR: 6.24; 95% CI, 2.75-14.18), insomnia (OR: 4.89; 95% CI, 2.16-11.05), and frailty (OR: 2.44; 95% CI, 1.75-3.40) were associated with malnutrition risk compared to well-nourished patients (p < 0.05). Median survival in patients with malnutrition risk was 21.3 months (range 14.1-28.4 95% CI) and median survival in patients who were defined as well nourished was not reached (p < 0.001). CONCLUSION: The risk of malnutrition was associated with a higher risk for all-cause mortality in older patients with cancer, and was associated with many geriatric syndromes, including polypharmacy, fall risk, frailty, insomnia, and depression.

Differentiation of lung and breast cancer brain metastases: Comparison of texture analysis and deep convolutional neural networks.

PURPOSE: Metastases are the most common neoplasm in the adult brain. In order to initiate the treatment, an extensive diagnostic workup is usually required. Radiomics is a discipline aimed at transforming visual data in radiological images into reliable diagnostic information. We aimed to examine the capability of deep learning methods to classify the origin of metastatic lesions in brain MRIs and compare the deep Convolutional Neural Network (CNN) methods with image texture based features. METHODS: One hundred forty three patients with 157 metastatic brain tumors were included in the study. The statistical and texture based image features were extracted from metastatic tumors after manual segmentation process. Three powerful pre-trained CNN architectures and the texture-based features on both 2D and 3D tumor images were used to differentiate lung and breast metastases. Ten-fold cross-validation was used for evaluation. Accuracy, precision, recall, and area under curve (AUC) metrics were calculated to analyze the diagnostic performance. RESULTS: The texture-based image features on 3D volumes achieved better discrimination results than 2D image features. The overall performance of CNN architectures with 3D inputs was higher than the texture-based features. Xception architecture, with 3D volumes as input, yielded the highest accuracy (0.85) while the AUC value was 0.84. The AUC values of VGG19 and the InceptionV3 architectures were 0.82 and 0.81, respectively. CONCLUSION: CNNs achieved superior diagnostic performance in differentiating brain metastases from lung and breast malignancies than texture-based image features. Differentiation using 3D volumes as input exhibited a higher success rate than 2D sagittal images.

Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study.

BACKGROUND: Outcomes are poor in patients with HER2-negative, advanced gastric or gastro-oesophageal junction adenocarcinomas. In this study, we investigated efficacy and safety of the first-in-class, afucosylated, humanised IgG1 anti-fibroblast growth factor receptor 2 isoform IIb (FGFR2b) monoclonal antibody bemarituzumab with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma. METHODS: In the randomised, double-blind, placebo-controlled phase 2 trial (FIGHT), patients aged 18 years and older with HER2 non-positive, FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 were recruited from 144 clinical sites across 17 countries. Patients with previous treatment with any selective inhibitor of the FGF-FGFR pathway were excluded. Eligible patients were randomly assigned (1:1), using permuted-block randomisation (block size of four) and a central interactive voice-web-based response system, stratified by geographical region, previous treatment with curative intent, and administration of mFOLFOX6 while being screened for FGFR2b status, to either bemarituzumab (15 mg/kg of bodyweight) or matched placebo intravenously every 2 weeks. All patients also received mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and 5-fluorouracil as a 400 mg/m2 bolus followed by 2400 mg/m2 over approximately 46 h) intravenously every 2 weeks. Patients were given treatment until disease progression (defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1), unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all patients randomly assigned to treatment). Safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, NCT03694522, and is now complete. FINDINGS: Between Nov 14, 2017, and May 8, 2020, 910 patients were screened and 155 were randomly assigned to the bemarituzumab (n=77) or placebo group (n=78). Median age was 60·0 years (IQR 51·0-67·0), 44 (28%) participants were women, 111 (72%) were men, 89 (57%) were Asian, and 61 (39%) were White. At the time of the primary analysis and at a median follow-up of 10·9 months (IQR 6·3-14·2), median progression-free survival was 9·5 months (95% CI 7·3-12·9) in the bemarituzumab group and 7·4 months (5·8-8·4) in the placebo group (hazard ratio [HR] 0·68 [95% CI 0·44-1·04; p=0·073). Common grade 3 or worse adverse events were decreased neutrophil count (23 [30%] of 76 in the bemarituzumab group vs 27 [35%] of 77 in the placebo group), cornea disorder (18 [24%] vs none), neutropenia (ten [13%] vs seven [9%]), stomatitis (seven [9%] vs one [1%]), and anaemia (six [8%] vs ten [13%]). Serious treatment-emergent adverse events were reported in 24 (32%) patients in the bemarituzumab group and 28 (36%) in the placebo group. Serious mFOLFOX6 treatment-related adverse events occurred in nine (12%) patients in the bemarituzumab group and in 15 (19%) patients in the placebo group. All-grade corneal events (adverse events of special interest) occurred in 51 (67%) patients in the bemarituzumab group and eight (10%) in the placebo group; grade 3 corneal events were reported only in 18 (24%) patients in the bemarituzumab group. Treatment-related deaths occurred in three patients in the bemarituzumab group (two due to sepsis, one due to pneumonia) and none in the placebo group. INTERPRETATION: In this exploratory phase 2 study, despite no statistically significant improvement in progression-free survival, treatment with bemarituzumab showed promising clinical efficacy. Confirmatory phase 3 trials of bemarituzumab plus mFOLFOX6 powered to demonstrate statistical significance are being investigated in patients with previously untreated, FGFR2b-overexpressing, advanced gastric or gastro-oesophageal junction adenocarcinoma. FUNDING: Five Prime Therapeutics.

The efficacy of BNT162b2 (Pfizer-BioNTech) and CoronaVac vaccines in patients with cancer.

Although vaccination is efficacious and prevents infection in the general population, there is limited data about Coronavirus disease-19 (Covid-19) occurrence after vaccination in cancer patients. It was aimed to evaluate the efficacy of BNT162b2 (Pfizer-BioNTech) and CoronaVac vaccines against Covid-19 in patients with cancer. In this single-center, retrospective, cross-sectional, and descriptive study, the data of cancer patients referred to the medical oncology clinic of a university hospital were analyzed. The sample of the study consisted of cancer patients who had Covid-19 or were vaccinated against Covid-19. A total number of 2578 patients were included in the study. Of the patients, 2000 have never been infected with severe acute respiratory syndrome coronavirus and 578 patients have had a positive reverse-transcription polymerase chain reaction (RT-PCR) for Covid-19. It was found that 2094 patients (81.2%) were fully vaccinated, and 484 patients (18.8%) did not receive full-dose vaccination. A statistically significant difference in Covid-19 occurrence was found between the patients who had full-dose vaccination or not (p = 0.000). In in-group comparisons of full-dose vaccinated patients, while no difference was observed between two doses of BNT162b2 (Pfizer-BioNTech) and three doses of CoronaVac (p = 0.432), a statistically significant difference was observed between all other groups (p < 0.005). When the data of 578 patients who experienced Covid-19 was analyzed, a statistically significant difference was observed between the groups who were full-dose vaccinated and those who were not (p = 0.000). It is recommended that this vulnerable patient group should be prioritized in vaccination programs, and full-dose vaccination (at least two doses of vaccines) should be completed as soon as possible.

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer in women worldwide. Ribociclib is now frequently used in the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer. CASE REPORT: A 54-year-old woman with breast cancer presented at a clinic in November 2017 with multiple lung and bone metastases. After receiving multiple lines of treatment due to disease progression, ribociclib and fulvestrant were initiated. Grade 4 toxicity was observed due to ribociclib during follow-up, and ribociclib was discontinued permanently.Management & Outcome: Given that liver transaminases and bilirubin elevation persisted despite discontinuation of the treatment, other reasons for liver toxicity were investigated. Abdominal MRI showed no liver metastases, although there was acute hepatitis. A liver biopsy was performed to determine the etiology. The pathology result was compatible with drug-induced acute fulminant toxic hepatitis. After liver biopsy, prednisolone treatment was initiated, after which the laboratory findings normalized. DISCUSSION: Although there are reported cases showing improvement in liver enzymes after ribociclib discontinuation, in our case, no recovery from hepatotoxicity was noticed. The treatment was changed to another hormonal pathway therapy option, exemestane. To the best of our knowledge, this is the first case in the literature reporting this rare side effect of ribociclib, which is a liver biopsy-proven fulminant hepatitis.

A comparison of anticholinergic burden in older patients with and without cancer.

Aim: To compare anticholinergic burden (ACB) in older patients with and without cancer and evaluate the effects of ACB on geriatric syndromes. Methods: A total of 291 patients from the geriatric clinic and 301 patients from the oncology clinic were evaluated. ACB <2 was categorized as low ACB and ACB ≥2 was categorized as high ACB. A comprehensive geriatric assessment was performed on patients from the geriatric clinic. Results: ACB scores were significantly higher in patients without cancer compared with those with cancer (p < 0.005). Number of falls and Geriatric Depression Scale 15 scores were higher and Mini-Nutritional Assessment and Barthel/Lawton activities of daily living scores were lower in geriatric patients with high ACB scores compared with those with low ACB scores (p < 0.005). Conclusion: It is crucial to understand the potential effects of ACB for rational drug use and optimum cancer management in older patients with cancer.

Lay abstract The elderly population is increasing rapidly worldwide, and most cancer patients are over the age of 65. In this age group, preexisting medical conditions other than cancer lead to the use of multiple drugs, which is defined as polypharmacy. Additionally, the anticholinergic burden (ACB) of the drugs affects cancer treatment in the elderly. This study investigated the frequency of polypharmacy and ACB in elderly patients with and without cancer and their relationship with geriatric syndromes such as depression, falls, nutritional and cognitive impairments. We found that ACB was higher in older patients without cancer than those with cancer and is related to increased falls, depressive symptoms, and impaired nutritional and functional status in older patients. Given the prevalence of cancer among older adults, it is crucial to understand the potential effects of the ACB for rational drug use and optimum cancer management in older patients with cancer.

Anxiety levels of breast cancer patients in Turkey during the COVID-19 pandemic.

Aim: To assess the anxiety levels of breast cancer patients during the COVID-19 pandemic. Materials & methods: A total of 298 patients completed the State-Trait Anxiety Inventory (STAI-S and STAI-T) and the Visual Analogue Scale for Anxiety (VAS) and VAS for Anxiety in COVID-19 (VAS-CoV). Results: 144 patients were in the high anxiety category for STAI-S, and 202 patients were in the high anxiety category for STAI-T. STAI-T score was significantly high in the metastatic group (p = 0.017). VAS-CoV score in the hormonotherapy group was significantly higher than in the no-treatment group (p = 0.023). There was a positive correlation between VAS-CoV and VAS levels (r = 0.708, p < 0.001), VAS-CoV and STAI-S and STAI-T scores (r = 0.402, p < 0.001; r = 0.185, p = 0.001, respectively), and a negative correlation between education years and STAI-T scores (r = -0.172, p = 0.003). Conclusion: The COVID-19 pandemic is related to high anxiety levels in breast cancer patients.

Lay abstract COVID-19 pandemic is related to rapidly rising anxiety levels worldwide. Because of the high mortality of COVID-19 in cancer patients, changing treatment routines and disruptions of the healthcare system, cancer patients are the most affected population in this situation. Anxiety among females and breast cancer patients tend to be high, although anxiety levels in cancer patients during the pandemic period varies according to the cancer type, treatment status and sociodemographic factors. This study assessed the effect of the COVID-19 pandemic on breast cancer patients' anxiety levels according to treatment status and stage of the disease. A total of 298 breast cancer patients completed the universally validated anxiety questionnaires. Results demonstrated high trait anxiety in breast cancer patients, particularly in the metastatic group. The current findings highlighted the importance of intensive assessment and close monitoring of breast cancer patients' psychological situations. It is crucial to provide psychological support to breast cancer patients to contribute to both treatment and follow-up processes during the pandemic.

Efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer.

Aim: To evaluate the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer. Methods: We retrospectively included 138 patients who were given trastuzumab-based chemotherapy as first-line treatment and analyzed the relationship between clinical response rates and maintenance treatment status and survival outcomes. Results: In the whole group, the median progression-free survival and overall survival were 10.2 and 16 months, respectively. Clinical response was obtained in 79% of patients. The median overall survival was 16.9 months in follow-up group and 19.0 months in the maintenance group in patients with clinical response. Continuation of maintenance trastuzumab created a significant survival advantage (p = 0.021). Eastern Cooperative Oncology Group performance status 2 (hazard ratio [HR]: 2.02), grade 3 (HR: 1.78) and more than four metastatic lesions (HR: 1.67) were determined as risk factors for death. Conclusion: We recommend the continuation of maintenance trastuzumab in patients with clinical response, but those with identified risk factors may not benefit from treatment because life expectancy may be low.

Gastric cancer has a poor prognosis despite available treatments. Inclusive studies are still needed with real-life data. Our research retrospectively evaluated the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer who received trastuzumab-based chemotherapy as first-line therapy. In total, 138 patients were included in this study. Clinical response to trastuzumab-based chemotherapy was obtained in 79% of the patients. We also divided the patients who had a clinical response into two groups according to whether they received maintenance therapy. In the present study, trastuzumab administration had compatible survival outcomes with recent studies. Continuation of trastuzumab maintenance treatment provided a survival advantage in patients with clinical response. We suppose that maintenance trastuzumab may be recommended in patients with clinical responses to the first-line treatment. Furthermore, Eastern Cooperative Oncology Group Performance Status 2, grade 3 and having more than four metastatic lesions were determined as risk factors for death. Therefore, although we recommend maintenance of trastuzumab in patients with clinical response, those with identified risk factors may not benefit from treatment.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy.

BACKGROUND: The role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. METHODS: Patients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. RESULTS: Fifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19-78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10-20 Gy), 27 Gy (range, 18-33 Gy) and 25 Gy (range, 25-30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. CONCLUSION: Our findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

Prevalence and co-incidence of geriatric syndromes according to the ECOG performance status in older cancer patients.

Background: Geriatric syndromes may be more common in older cancer patients than in those without cancer. Geriatric syndromes can cause poor clinical outcomes. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is often used as a clinically reported functional status score in oncology practice. Methods: Our study was designed as a cross-sectional study and included 218 older cancer patients. This study aimed to determine the prevalence and relationship of geriatric syndromes according to the ECOG-PS in older cancer patients. Results: The mean age of 218 participants was 73.0 ± 5.6 years, with 47.7% being women and 52.3% men in our study. ECOG-PS 0, 1, and 2 groups contained 51, 39, and 10% of the patients, respectively. The mean number of geriatric syndromes in the ECOG 0, 1, and 2 groups was 2.3 ± 2.2, 4.3 ± 2.4, and 5.7 ± 2.1, respectively (p < 0.001). After adjusting for age and sex, it was determined that dynapenia was 2.9 times, probable sarcopenia was 3.5 times, frailty was 4.2 times, depression was 2.6 times, malnutrition was 3.3 times, insomnia 2 was.2 times, falls was 2.5 times, and the risk of falling (TUG) was 2.4 times more likely in those with ECOG-PS 1 compared to those with ECOG-PS 0. In addition, it was found that dynapenia was 6 times, probable sarcopenia was 6.8 times, frailty was 10.8 times, depression was 3.3 times, malnutrition was 6.3 times, the risk of falling (Tinnetti Balance) was 28 times, and the risk of falling (TUG) was 13.6 times more likely in those with ECOG-PS 2 compared to those with ECOG-PS 0. Conclusion: Our study found that the prevalence of geriatric syndromes increased as the ECOG-PS increased. Geriatric syndromes and their co-incidence were common in older cancer patients, even in normal performance status. Oncologists should incorporate geriatric syndromes into the decision-making process of cancer treatment to maximize the impact on clinical outcomes in older patients with cancer.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Stem cell markers: A guide to neoadjuvant therapy in breast carcinomas.

Aim: This study aims to investigate potential associations between the stem cell population and the degree of tumor regression in breast carcinomas treated with neoadjuvant therapy. Settings and Design: The study included 92 patients with breast carcinoma who received neoadjuvant therapy. Tumor regression was defined based on Miller and Payne grading system. Patients with grade 1 or 2 regression on a 5-point scale were included in group 1 (n = 37), grade 3 regression in group 2 (n = 32), and grade 4 or 5 regression in group 3 (n = 23). Materials and Methods: Immunohistochemical staining was performed on paraffin block sections of every case using CD44, CD24, CD29, CD133, ID4, and ALDH1 antibodies to detect stem cells. Statistical Analysis Used: IBM Statistical Package for the Social Sciences (SPSS), version 23.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analyses, and a P value less than 0.05 was considered statistically significant. Results: Histologically high-grade tumors are more common in the near-complete/complete response group (P = 0.004). HER2-positive tumors were more common in the complete/near-complete response group (P = 0.054). Tumor cells positive for stem cell markers CD44 and CD24 were more common in the poor response group (P = 0.027 and P = 0.001, respectively). CD29 expression was reduced in the posttreatment residual tumor tissue in the near-complete/complete response group. Conclusion: High CD44 and CD24 expression may be a predictor of poor response/nonresponse to neoadjuvant therapy in breast carcinomas. Background: In recent years, stem cells have been defined as the main cell population responsible for resistance to anticancer therapies.