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.

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.

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.

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.

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.

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.

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.

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .

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.

Local interventions for colorectal cancer metastases to liver and lung.

BACKGROUND: Colorectal cancer is a common cause of cancer-related deaths. About 1/3 of all cases present with distant metastasis, with the liver as the leading site and the lung as the most common extra-abdominal site. AIMS: It was aimed to evaluate the clinical characteristics and the outcomes of colorectal cancer patients with liver or lung metastasis who had received local treatments. METHODS: This is a retrospective, cross-sectional, and descriptive study. The study was performed with colorectal cancer patients that referred to the medical oncology clinic of a university hospital between December 2013 and August 2021. RESULTS: A total number of 122 patients who have received local treatments were included. Radiofrequency ablation was applied in 32 patients (26.2%), metastasis was surgically resected in 84 patients (68.9%), and stereotactic body radiotherapy was preferred in six patients (4.9%). At the first follow-up control after completion of local or multimodal treatment, no residual tumor was determined with radiological assessment in 88 patients (72.1%). The median progression-free survival (16.7 months vs 9.7 months) (p = .000) and the median overall survival (37.3 months vs 25.5 months) (p = .004) of these patients were significantly better than the patients with residual disease. CONCLUSIONS: Local interventions that are applied to highly selected patients may improve the survival of metastatic colorectal cancer patients. A close follow-up after local therapies is important to diagnose recurrent disease because repeated local interventions may be possible to achieve better outcomes.

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.

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 effect of sarcopenia on erlotinib therapy in patients with metastatic lung adenocarcinoma.

Erlotinib, a tyrosine kinase inhibitor, has been shown to improve the survival of patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Sarcopenia is a status with increasing importance in lung cancer, and it may predict a poor prognosis. We aimed to evaluate the impact of sarcopenia on erlotinib therapy and prognosis in patients with EGFR-mutated (exon 19 or 21 L858R) metastatic lung adenocarcinoma. Sarcopenia was defined as skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men. The patient characteristics, inflammation parameters, clinical and survival outcomes of the erlotinib therapy were examined according to sarcopenia status. We also analyzed the erlotinib treatment-related toxicity. Seventy-two patients were included in our retrospective study, and the mean age of the patients was 63.7 years. A total of 39 (54.2%) patients were diagnosed with sarcopenia. Patients with sarcopenia had a poor prognosis and had a shorter median progression-free survival (PFS) than patients without sarcopenia (10.5 months vs. 21.8 months, p=0.002). Sarcopenia (HR 2.08) and C-reactive protein > 6.5 mg/L (HR 2.57) were determined as independent poor prognostic factors for PFS of erlotinib therapy. Treatment-related toxicity occurred in 34.7% of patients treated with erlotinib, and sarcopenia did not significantly affect treatment-related toxicity. We also found that sarcopenia significantly affected the response to erlotinib. The expected survival outcomes may be low when erlotinib therapy is used in patients with sarcopenia and metastatic lung adenocarcinoma. This study showed that survival and clinical outcomes could be better predicted by detecting sarcopenia in patients with lung cancer using erlotinib.

Evaluation of toxic effects of chemotherapy in lung malignancies on cerebral white matter using diffusion tensor imaging.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of morbidity and mortality. Carboplatin and cisplatin based regimens are used in the treatment of NSCLC. The aim of the study was to find out whether there is a difference in white matter (WM) changes between two platinum-based chemotherapy agents using diffusion tensor imaging (DTI). PATIENTS AND METHODS: 25 patients who received chemotherapy for NSCLC and 27 age-matched healthy controls were enrolled in the study. Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD) values of the study population were measured from 11 regions of interest in pre-chemotherapy and post-chemotherapy MRI data. RESULTS: Cisplatin group showed a significant decrease in the FA of the inferior longitudinal fasciculus (P = 0.028). Carboplatin group showed a significant FA decrease and RD increase in the forceps minor (P = 0.022 and P = 0.011, respectively), and a significant reduction in AD and increase in MD in frontal white matter (WM) (P = 0.008 and P = 0.029, respectively). In comparison of post chemotherapy DTI values of the two groups, carboplatin group showed lower FA, and higher MD and RD values than cisplatin group in parieto-occipital WM (P = 0.034, P = 0.034, P = 0.029, respectively). CONCLUSIONS: The findings of the study suggest that subtle effects of chemotherapy detectable with DTI may emerge after the treatment. In addition, carboplatin regimen may have more impact on WM than cisplatin regimen.

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.

First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer.

Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.

Diffusion Tensor Imaging Can Discriminate the Primary Cell Type of Intracranial Metastases for Patients with Lung Cancer.

PURPOSE: Histopathological differentiation of primary lung cancer is clinically important. We aimed to investigate whether diffusion tensor imaging (DTI) parameters of metastatic brain lesions could predict the histopathological types of the primary lung cancer. METHODS: In total, 53 patients with 98 solid metastatic brain lesions of lung cancer were included. Lung tumors were subgrouped as non-small cell carcinoma (NSCLC) (n = 34) and small cell carcinoma (SCLC) (n = 19). Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) values were calculated from solid enhanced part of the brain metastases. The association between FA and ADC values and histopathological subtype of the primary tumor was investigated. RESULTS: The mean ADC and FA values obtained from the solid part of the brain metastases of SCLC were significantly lower than the NSCLC metastases (P < 0.001 and P = 0.003, respectively). ROC curve analysis showed diagnostic performance for mean ADC values (AUC=0.889, P = < 0.001) and FA values (AUC = 0.677, P = 0.002). Cut-off value of > 0.909 × 10-3 mm2/s for mean ADC (Sensitivity = 80.3, Specificity = 83.8, PPV = 89.1, NPV = 72.1) and > 0.139 for FA values (Sensitivity = 80.3, Specificity = 54.1, PPV = 74.2, NPV= 62.5) revealed in differentiating NSCLC from NSCLC. CONCLUSION: DTI parameters of brain metastasis can discriminate SCLC and NSCLC. ADC and FA values of metastatic brain lesions due to the lung cancer may be an important tool to differentiate histopathological subgroups. DTI may guide clinicians for the management of intracranial metastatic lesions of lung cancer.

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.

Diagnostic performance of apparent diffusion coefficient values for the differentiation of intrahepatic cholangiocarcinoma from gastrointestinal adenocarcinoma liver metastases.

BACKGROUND: We aimed to investigate whether there is a difference between intrahepatic cholangiocarcinoma (IHCC) and liver metastases of gastrointestinal system (GIS) adenocarcinoma in terms of apparent diffusion coefficient (ADC) values. PATIENTS AND METHODS: From January 2018 to January 2020, we retrospectively examined 64 consecutive patients with liver metastases due to gastrointestinal system adenocarcinomas and 13 consecutive IHCC in our hospital's medical records. After exclusions, fifty-three patients with 53 liver metastases and 10 IHCC were included in our study. We divided the patients into two groups as IHCC and liver metastases of GIS adenocarcinoma. For mean apparent diffusion coefficient (ADCmean) values, the region of interests (ROI) was placed in solid portions of the lesions. ADCmean values of groups were compared. RESULTS: The mean age of IHCC group was 62.50 ± 13.49 and mean age of metastases group was 61.15 ± 9.18. ADCmean values were significantly higher in the IHCC group compared to the metastatic group (p < 0.001). ROC curves method showed high diagnostic accuracy (AUC = 0.879) with cut-off value of < 1178 x 10-6 mm2/s for ADCmean (Sensitivity = 90.57, Specificity = 70.0, positive predictive value [PPV] = 94.1, negative predictive value [NPV] = 58.3) in differentiating adenocarcinoma metastases from IHCC. CONCLUSIONS: The present study results suggest that ADC values have a potential role for differentiation between IHCC and GIS adenocarcinoma liver metastases which may be valuable for patient management.