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Objectives: Brain imaging of regional metabolic changes in cancer patients can provide insights into cancer biology. We aimed to detect regional metabolic changes in the brains of untreated lung cancer patients without brain metastases using 2-deoxy-2-[18F]fluoroglucose PET/computed tomography., Methods: The study included 44 lung cancer patients and 17 non-cancer patients as controls. Standardized uptake value (SUV) mean values of 68 different brain regions were recorded, and their ratios to whole brain and brainstem SUVmean were calculated., Results: Comparisons between the groups showed significant reductions in the frontal lobe, inferior temporal gyrus, and right cingulate and paracingulate gyrus ratios in the patient group. Conversely, the right nucleus caudatus and right pallidum ratios were elevated. Correlation analysis with total lesion glycolysis (TLG) revealed positive correlations in the basal ganglia, right insula, amygdala, and right hippocampus ratios. Negative correlations were observed in the left frontal lobe and some temporal and parietal regions., Conclusions: While most brain regions showed reduced metabolism, potentially due to tumor-brain glucose competition, others were preserved or positively correlated with TLG, suggesting a link to poor prognosis. The reduced metabolism in the frontal lobe might be associated with depression and cognitive decline in cancer patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences., Method: The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series., Results: One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival., Conclusion: This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Bloom syndrome (BS) is a rare autosomal recessive disorder caused by a loss-of-function mutation in the BLM gene encoding an RecQ helicase involved in DNA repair and maintenance of chromosomal stability. In patients with BS, significant sensitivity to both DNA-damaging chemotherapy (CT) and ionizing radiation complicates the management of neoplasms by exacerbating comorbidities and predisposing to toxicities and poor outcomes., Case Report: A 30-year-old female patient diagnosed with BS who presented with early-stage triple-negative breast cancer was treated with four cycles of doxorubicin (60 mg/m 2 ) and cyclophosphamide (600 mg/m 2 ) followed by weekly paclitaxel (80 mg/m 2 ) for 12 weeks as the chemotherapy protocol and a total of 5000 cGy curative radiotherapy (RT). Due to pancytopenia 8 months after completion of therapy, bone marrow biopsy and aspiration were performed, and a diagnosis of myelodysplastic syndrome with excess blasts 2 (MDS-EB2) was made. Two courses of the azacitidine (75 mg/m 2 ) protocol were administered every 28 days in the hematology clinic. Two weeks after CT the patient was transferred from the emergency department to the hematology clinic with the diagnosis of pancytopenia and febrile neutropenia. She died at the age of 33 due to sepsis that developed during follow-up., Conclusion: Due to the rarity of BS, there is no prospective trial in patients with cancer and no evidence base upon which to design treatment programs. For these reasons, it is strongly recommended that patients receive multidisciplinary care, with precise assessment and discussion of the indication and an adequate dose of DNA-damaging agents such as chemotherapy and ionizing radiation., (© 2024. The Author(s).)

Objectives: Synthetic data may proxy clinical data. At the absence of direct clinical data, this study aimed to compare Irinotecan and Ifosfamide (II) with Topotecan in synthetic, recurrent small cell lung cancer (SCLC) patients within a simulated clinical trial., Materials and Methods: Two simulation stages were conducted. Initially, 200 recurrent SCLC cases were simulated to replicate a previous phase 3 trial, testing the utility of Cox proportional hazards model and simulation methodology together, where patients were randomized to receive Cyclophosphamide, Adriamycin, Vincristine (CAV) or Topotecan. In the second stage, 600 recurrent SCLC patients were simulated and randomized to compare Topotecan versus II in terms of overall survival (OAS), using Reinforcement Learning (RL) and Cox proportional hazards model., Results: CAV versus Topotecan comparison showed no statistical difference in overall survival (hazard ratio (HR): 0.89, 95% CI: 0.67-1.18, P = 0.418), aligning with the original clinical trial. For the Topotecan versus II comparison, the RL framework significantly favored the II arm (mean reward points: 193.43 versus - 251.82, permutation P < 0.0001). Likewise, II arm exhibited superior median OAS compared to Topotecan arm (11.12 versus 6.30 months). HR was 0.44 (95% CI: 0.38-0.52) with P < 0.0001, in favor of II., Conclusion: Artificial trial results for CAV versus Topotecan matched the original trial, confirming indifference of OAS. Additionally, II yielded superior overall survival compared to Topotecan in recurrent SCLC patients. These demonstrate the potential of RL and simulation in conjunction with Cox modelling for similar studies. However, definitive conclusions necessitate a randomized clinical trial between II and Topotecan in this patient cohort., (© 2024. The Author(s).)

Introduction: Ado-trastuzumab emtansine (T-DM1) is employed in the treatment of patients with HER2-positive breast cancer. The most common side effects are fatigue, diarrhoea, anaemia, transaminase elevation and drug-induced thrombocytopenia. This report describes a patient with metastatic breast cancer who developed drug-induced lupus due to T-DM1., Case Report: A 54-year-old woman was diagnosed with breast cancer in March 2018. She underwent modified radical mastectomy and axillary lymph node dissection (pT2N1aM0). Following supraclavicular lymph node metastasis in May 2018, she received 8 cycles of docetaxel, trastuzumab, and pertuzumab. In December 2020, the patient presented with axillary and intra-abdominal lymph node metastases, along with bone metastases observed on PET/CT scan. Treatment with T-DM1 and zoledronic acid was initiated. After 18 months on T-DM1, she developed drug-induced lupus. Her symptoms resolved with hydroxychloroquine treatment and discontinuation of T-DM1., Discussion: Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature., Competing Interests: Author ContributionConcept — OY and MA. Design — OY and MA. Pathology figüre ZÇ collection: MKE, TA. Supervision — all authors. Data collection and/or processing — all authors. Analysis and/or interpretation — AFG, MA. Literature search — OY, AFG, MKE, TA. Writing — OY, MA. Radiological Imaging provision ÖÇ. Critical reviews — all authors. All authors reviewed and approved the final version of the manuscript. Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Lorlatinib is a potent third-generation anaplastic lymphoma kinase/c-ros oncogene 1 (ALK)/ROS1 oral tyrosine kinase inhibitor that has broad coverage of acquired resistance mutations and is currently indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ALK-positive., Case Report: In this case, we aimed to present the safety and effectiveness of lorlatinib use in a patient diagnosed with ALK-positive metastatic NSCLC who underwent hemodialysis 3 days a week., Management & Outcome: A 76-year-old female patient has been undergoing regular hemodialysis for about 2 years. A brain magnetic resonance imaging (MRI) was taken due to headache and a mass was detected. She was diagnosed with lung adenocarcinoma as a result of excisional biopsy. Positron emission tomography/ computed tomography (PET/CT) showed a mass in the hilar region of the left lung and multiple lymphadenopathy in the mediastinum. In February 2023, 100 mg lorlatinib was started daily. There was no significant regression in PET-CT and no brain MRI residue during follow-up. The patient has been continuing lorlatinib for approximately 1 year with almost complete response, with no side effects other than hypercholesterolemia., Discussion: We presented our experience using lorlatinib in a patient with metastatic ALK + NSCLC undergoing hemodialysis. Although the dosage of lorlatinib in hemodialysis patients is still controversial, our case report indicates that 100 mg lorlatinib was safe in this patient., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: We wanted to present a rare case of metastatic grade 2 spinal ependymoma with an atypical course at the time of diagnosis. Temozolomide plus capecitabine chemotherapy was started in May 2018 on a 30-year-old female patient with sacral ependymoma who had extensive lung metastases at the time of diagnosis. The patient remained in remission for approximately 29 months, and the current chemotherapy was continued until it progressed in November 2020. According to this case report, a combination of temozolomide and capecitabine may be the best treatment option for ependymoma patients., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Objective: This study aimed to assess the efficacy and safety of FOLFIRI and paclitaxel in patients with advanced gastric cancer (AGC) who were previously treated with first-line modified docetaxel, cisplatin, 5-fluorouracil (mDCF), or 5-fluorouracil, oxaliplatin, docetaxel (FLOT)., Methods: Patients who received a triplet regimen in the first line setting and were treated with FOLFIRI or paclitaxel in the second-line treatment were included., Results: The study included 198 patients, with 115 receiving FOLFIRI and 83 receiving paclitaxel. The median age was 58 (range = 24-69). The median progression-free survival (mPFS) was 5.2 [95% confidence interval (CI) = 4.4-5.5] months in the FOLFIRI arm, and 4.1 (95% CI = 3.3-4.6) months in the paclitaxel arm ( p  = .007). The median overall survival (mOS) was 9.4 (95% CI = 7.4-10.5) months in the FOLFIRI arm and 7.2 (95% CI = 5.6-8.3) months in the paclitaxel arm ( p  = .008). Grade 3-4 neuropathy was higher in patients receiving paclitaxel compared to those receiving FOLFIRI ( p  = .04). Grade 3-4 diarrhea was 8% in the FOLFIRI arm and 2.4% in the paclitaxel arm ( p  = .02)., Conclusion: Beyond progression with docetaxel-based triplet chemotherapy, FOLFIRI may be preferred as a second-line treatment over paclitaxel due to its longer mPFS and mOS.

Purpose: Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers., Methods: A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them., Result: The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0-65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9-27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5-40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9-16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062)., Conclusion: Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. The Author(s).)

Aim: Endocrine therapy (ET) plus cyclin-dependent kinase (CDK) 4/6 inhibitors is a standard treatment for hormone receptor (HR) positive HER-2-negative metastatic breast cancer patients. In this study, we aimed to investigate the effect of body mass index (BMI) on progression-free survival (PFS) in patients receiving ET plus CDK 4/6 inhibitors. Materials & methods: Patients with metastatic HR-positive breast cancer receiving CDK 4/6 inhibitors were included in the study. A total of 116 patients were retrospectively evaluated. Patients were divided into three groups according to BMI level: normal weight (group 1) 18.5-24.9 kg/m 2 , overweight (group 2) 25-29.9 kg/m 2 and obese (group 3): ≥30 kg/m 2 . Median follow-up was 10.83 months. Comparisons of PFS and BMI categories were performed by Kaplan-Meier curve and log-rank test. Results: PFS was 9.3 (5.3-13.4) months in normal weight patients and 11.1 (9.7-12.56) months in obese patients and was not reached in overweight patients. This difference was statistically significant ( p  = 0.02). Conclusion: Low BMI has been shown to have a negative prognostic effect on survival in patients with metastatic breast cancer and overweight patients had a longer PFS.

Purpose: The prognostic nutritional index (PNI), like other systemic inflammatory markers, has been shown to be a prognostic factor in various cancer patients. In this study, we aimed to show whether PNI calculated before adjuvant chemotherapy is a prognostic factor for overall survival (OS) and disease-free survival (DFS) in patients with lymph node-positive stage II-III gastric cancer., Methods: The PNI was calculated using the albumin and lymphocyte count. The PNI cut-off value was found to be 39.5. They were divided into two groups as being ≤ 39.5 (PNI low group) and > 39.5 (PNI high group)., Results: Our study included 168 patients with lymph node-positive stage II-III gastric cancer who received adjuvant chemotherapy. Of the patients, 116 (69.0%) were 65 years or younger, and 52 (31.0%) were over 65 years old. Of the patients, 117 (69.6%) were pT3, 51 (30.4%) were pT4. Seventy-three (43.4%) patients had pN1-2 disease and 95 (56.6%) patients had pN3 disease. The number of stage II patients was 73 (43.5%) and the number of stage III patients was 95 (56.5%). There were 73 patients with PNI ≤ 39.5 and 95 patients with PNI > 39.5. The mOS of the patients with low PNI group was 39.5 months, while the OS of the patients with high PNI group was 96.8 months (p = 0.002). In the group of patients with PNI low group, mDFS 24.4 months was significantly higher than those with PNI high group was 50.7 months (p = 0.021). The PNI score was statistically significant in univariate and multivariate analyzes for both DFS and OS., Conclusion: PNI can be used as an independent prognostic factor for both OS and DFS in patients lymph node-positive, stage II-III gastric cancer who will receive adjuvant chemotherapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: We aimed to evaluate the effect of concomitant proton pump inhibitors (PPI) use with nivolumab on survival outcomes in metastatic renal cell carcinoma (mRCC) in second-line setting., Methods: The study was designed as a multicenter and retrospective involving patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy. One hundred and nine patients with mRCC were divided into two groups based on whether they use PPI concomitantly with nivolumab: concomitant PPI users and non-users. Overall survival (OS) and progression-free survival (PFS) were compared between the groups with and without concurrent PPIs., Results: Of 109 patients in our study, 59 were not using PPI concomitantly with nivolumab and 50 were using PPI concomitantly. The median PFS was 6.37 (5.2-7.5) months in the concomitant PPI group and 9.7 (4.5-15) months in the non-users (p = 0.03). The median OS was 14.6 (7.1-22.1) months in patients on PPI concurrently with nivolumab and 29.9 (17.1-42.7) months in the non-users (p = 0.01). Accordingly, PPI use for PFS (Non-use vs. Use = HR: 0.44, 95%Cl 0.28-0.96, p = 0.014) and PPI use for OS (Non-use vs. Use = HR: 0.68, 95%Cl 0.22-0.88, p = 0.01) were found to be as independent risk factors., Conclusions: Concomitant use of PPIs is associated with worse survival outcomes in patients with mRCC treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs in such patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Not all RAS wild-type metastatic colorectal cancer (mCRC) patients experience the same benefit from anti-epidermal growth factor receptor (EGFR) treatments. Studies have shown that nuclear factor-κB (NF-κB), hypoxia-inducible factor-1α (HIF-1α), interleukin 8 (IL-8) and transforming growth factor β (TGF-β) may be therapeutic targets for mCRC. The aim of this study was to clarify the prognostic value of NF-κB, HIF-1α, IL-8, and TGF-β expression in patients with left-sided mCRC receiving EGFR inhibitors., Methods: Patients with RAS wild-type, left-sided mCRC treated with anti-EGFR on the first line between September 2013 and April 2022 were included. Immunohistochemical staining for NF-κB, HIF-1α, IL-8 and TGF-β was performed from tumor tissues of 88 patients. Patients were divided into NF-κB, HIF-1α, IL-8 and TGF-β expression positive and negative group, moreover, expression positive group were also divided into two group as expression intensity low and high group. The median follow-up was 25.2 months., Results: Median progression-free survival (PFS) was 8.1 (6-10.2) months in the cetuximab group, 11.3 (8.5-14) months in the panitumumab group (p = 0.09). Median overall survival (OS) was 23.9 (4.3-43.4) months in the cetuximab group, 26.9 (15.9-31.9) months in the panitumumab group (p = 0.8). Cytoplasmic NF-κB expression was present in all patients. The mOS was 19.8 (11-28.6) months in NF-κB expression intensity low group and 36.5 (20.1-52.8) months in high group (p = 0.03). The mOS of the HIF-1α expression negative group was significantly longer compared with expression positive group (p = 0.014). There was no significant difference in IL-8 and TGF-β expression status on mOS and mPFS (for all, p > 0.05). Positive expression of HIF-1α was poor prognostic for mOS in the univariate analysis (HR:2.7, 95% CI 1.18-6.52, p = 0.02) and in multivariate analysis (HR 3.69, 95% CI 1.41-9.6, p = 0.008). High cytoplasmic expression intensity of NF-κB was found to have a good prognostic value for mOS (HR 0.47, 95% CI 0.26-0.85, p = 0.01)., Conclusion: High cytoplasmic expression intensity of NF-κB and negative expression of HIF-1α could be a good prognostic marker for mOS in RAS wild-type left-sided mCRC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC., Objective: This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC., Material and Methods: In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis., Results: The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031)., Conclusions: We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

Introduction: Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown a different adverse effect. In this case, persistent grade 3 hepatoxicity was observed after ribociclib. Therefore, ribociclib therapy was stopped, and then palbociclib was introduced. Transaminase levels returned to normal by switching to palbociclib therapy., Case Report: 71-year-old postmenopausal female patient with luminal subtypes of metastatic breast cancer treated with ribociclib., Management & Outcome: Grade 3 hepatotoxicity secondary to ribociclib developed. She was successfully treated with palbociclib 125 mg., Discussion: In our case, palbociclib was started with a full dose, to increase treatment success. Starting with a 125 mg dose was not cause any toxicity. Nevertheless, laboratory follow-up is required in terms of neutropenia and increased transaminases.

Background: Hepatocellular carcinoma (HCC) is a significant health problem, and the associated mortality rate is increasing., Aim: We aimed to determine the clinical characteristics and prognosis for HCC in member countries of the OncoBridge Study Group., Methods: We recruited 630 patients diagnosed with HCC between 2013 and 2019 from 4 countries (Türkiye, Russia, Georgia, and Greece). Univariate and multivariate analyses were conducted to investigate clinical and laboratory prognostic factors. Receiver operating characteristic (ROC) analysis was used to determine the prognostic value of the neutrophil to lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) value., Results: The 3 most common etiological factors were hepatitis B infection (39.7%), hepatitis C virus infection (17.0%) and non-alcoholic fatty liver disease (9.0%). Median overall survival for the whole group was 25 [95% confidence interval (CI): 15.7-34.2] months. Cut-off values for AFP and NLR were accepted as 200 ng/mL and 3.45, respectively. The area under the ROC curve values for AFP, NLR and NLR+AFP were 0.625 (95% CI: 0.547-0.704), 0.589 (95% CI: 0.512-0.667) and 0.657 (95% CI: 0.583-0.731). From the multivariate analysis, advanced tumour size, lymph node involvement and metastasis (TNM) stage, presence of cirrhosis, high AFP, and high NLR values were associated with poor survival., Conclusion: AFP, NLR, advanced TNM, and presence of cirrhosis may predict prognosis in patients with HCC. Studies involving more countries are needed to corroborate these findings., (Copyright © Authors 2023; Licensee: World Health Organization. EMHJ is an open access journal. This paper is available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Purpose: In this study, we aimed to evaluate the prognostic significance of adipose tissue distribution and metabolic activity in PET/CT to predict survival in patients with metastatic colorectal cancer (mCRC)., Methods: The volume, density (HU), and FDG uptake (standardized uptake value (SUV)) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and maximum FDG uptake of the tumor tissue were measured. Subcutaneous adipose tissue of volume-to-density ratio (SAT ratio) was calculated., Results: The median OS for the patients with SAT ratio value <  -1.1 and ≥  -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). During follow-up, 69 patients experienced disease progression. The median progression-free survival (PFS) was 11.03 months (95% CI: 9.11-12.95). Median PFS for patients with tumor SUV max value < 11.5 and ≥ 11.5 were 9.2 (95% CI 7.25-11.27) and 12.6 (95% CI 10.02-15.27) months, respectively (p = 0.14). Forty-eight patients received bevacizumab therapy. VAT SUV mean (HR: 0.09; 95% CI 0.01-0.52, p = 0.008) was significantly associated with PFS in patients receiving bevacizumab. SAT ratio was the significant parameter for the OS (HR: 0.58; 95% CI 0.33-1.01, p = 0.05) and PFS (HR: 1.99; 95% CI 1.02-3.91, p = 0.043)., Conclusions: SAT ratio was an independent prognostic factor for survival in patients with mCRC. Higher SAT volume is correlated with longer survival in mCRC patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study is aimed at evaluating the relationship between dietary and serum advanced glycation end-products (AGEs) with serum inflammatory and oxidative stress biomarkers in breast cancer (BC)., Methods: A sample of BC patients was followed for 12 months (March 2020-January 2022). Three-day food consumption record and serum samples were taken before surgery (T1), before chemotherapy (T2), at the 6 th month of chemotherapy (T3), and at the 12 th month of chemotherapy (T4). Dietary AGE intake was represented by carboxymethyl lysine (dCML). Serum levels of CML, inflammation, and oxidation biomarkers were determined with biochemical blood tests. The results were compared according to human epidermal growth factor receptor-2 (HER2) status., Results: Thirty-two women with BC and 32 age and body mass index-matched healthy women participated. No significant correlation was found between dCML and serum CML, inflammatory or oxidative stress biomarkers at T1, T2, and T4. A weak positive correlation was demonstrated between dCML and serum malondialdehyde levels (rho=0.355, p=0.046) at T3. The serum CML, inflammation, and oxidation biomarker levels of the HER2- group were significantly higher than those of the HER2+ group at T1., Conclusion: This study suggests that there is limited correlation between dCML and serum inflammation and oxidative stress biomarkers in BC patients. Inflammation and oxidative biomarker levels appear to decline with treatment although dietary and serum AGE levels show not a corresponding significant decline. The HER2- subtype appears to be associated with higher dietary and serum AGEs and higher inflammatory and oxidative stress biomarkers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: It is red cell distribution width (RDW) that has been reported to show an inflammatory response which has been studied recently. The aim of this study is to investigate whether the pre-treatment RDW in patients using first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) with the diagnosis of metastatic renal cell carcinoma (mRCC) predicts treatment response and is a prognostic factor or not., Methods: About 92 patients diagnosed with mRCC who were being treated with sunitinib or pazopanib in the first line between January 2015 and June 2021 were included in the study. The patients were divided into 2 groups, as being ≤15.3 and >15.3, according to the RDW cut-off value calculated by ROC analysis., Results: The mOS of patients with a RDW of ≤15.3% was 45.0 (30.0-59.9) months, and of 21.3 (10.4-32.2) in those with a RDW of >15.3%. This difference was statistically significant (p < 0.001). In the group of patients with a RDW of ≤15.3, median progression free survival (mPFS) (38.04 [16.3-59.7] months) was found to be significantly higher than those with a RDW of >15.3 (17.1 [11.8-22.5] months) (p = 0.04). In multivariate analysis, RDW level (≤15.3, >15.3), was determined to be prognostic markers (p = 0.022)., Conclusion: In mRCC patients, the RDW value measured before first-line VEGFR TKI therapy is an independent prognostic marker., Competing Interests: None

Background: Small-cell lung cancer (SCLC) has a poor prognosis. For the last 30 years, first-line systemic treatment has remained unaltered. After the integration of ımmunotherapy, a new first-line gold standard, atezolizumab in combination with carboplatin plus etoposide, was approved in extensive-disease SCLC (ED-SCLC) in 2019., Materials and Methods: First-line randomized controlled studies that investigated anti-programmed cell death protein 1 (PD-1)/PD-1 ligand-1 (PD-L1) and anti-T-lymphocyte-associated protein 4 (CTLA-4) agents in combination with platinum plus etoposide (EP) were scoured. A total of six studies (two - anti-CTLA-4 and four - anti-PD1/PD-L1) were included and classic and network meta-analyses (NMAs) were performed., Results: Fixed model for overall survival (OAS) in the PD-1- or PD-L1-treated subgroup yielded a hazard ratio (HR) of 0.746 with a 95% confidence interval (CI) =0.662-0.840 and in the CTLA-4-treated subgroup a HR of 0.941 with a 95% CI = 0.816-1.084 for the immune therapy + chemotherapy versus chemotherapy comparison (CTLA-4-based versus PD-1- or PD-L1-based groups' comparison of OAS effect Q = 6.05, df = 1, P = 0.014). NMA showed that all chemotherapy + immunotherapy combinations were equally potent and more efficient than PE in terms of OAS and progression-free survival (PFS). Rank probability plots demonstrated nivolumab + EP as the most probable effective treatment modality in terms of OAS and PFS., Conclusion: The usage of anti-PD1/PD-L1 immunotherapy agents results in significant OAS advantage, and anti-PD1/PD-L1 agents are superior to anti-CTLA-4 approach in combination with platinum plus etoposide regimen in ED-SCLC., Competing Interests: None

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., (© 2023. The Author(s).)

Aim: To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC., Methods: We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users., Results: Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94-27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9 months (95% CI: 7.5-14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use (p = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib., Conclusion: Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: The aim of this study was to evaluate the presence of small bowel wall edema (SBWE) on computed tomography (CT) images in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib and to investigate the relationship between the presence of SBWE and survival., Materials and Methods: We retrospectively evaluated the presence of SBWE on CT images of 27 mRCC patients who received at least one cycle of sunitinib. Then, we analyzed the relationship between the presence of SBWE and progression-free survival (PFS) and overall survival (OS)., Results: All 27 patients had SBWE on at least one CT scan. The median value of SBWE thickness was 2.5 mm. SBWE thickness was ≤2.5 mm in 13 patients (group A) and >2.5 mm in 14 patients (group B). The median OS was significantly higher in group B (55 vs. 18 months, respectively, P = 0.02). Although it was not statistically significant (13 vs. 8 months, respectively, P = 0.69), the median PFS was longer in group B than in group A., Conclusions: This study showed that sunitinib treatment caused SBWE in all patients with mRCC who received the drug. Also, this study demonstrated an association between higher SBWE thickness and better survival outcomes., Competing Interests: None

Dietary antioxidant capacity (dTAC) and dietary inflammatory index (DII) are commonly used to assess nutrition. This prospective study examined dTAC, DII, and serum biomarkers in women with breast cancer (BC). Patients were followed-up before surgery (T 1 ), before chemotherapy (T 2 ), at 6 th (T 3 ) and 12 th months of chemotherapy (T 4 ). Serum tumor necrosis factor alpha, interleukin 1β, interleukin 6, protein carbonyl, malondialdehyde, total antioxidant capacity (TAC), and total oxidant status levels were analyzed. Dietary antioxidant intake, dTAC, and DII were determined using a three-day dietary record. dTAC was calculated using vitamin C equivalent (VCE), oxygen radical absorption capacity (ORAC), trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), and ferrous ion reducing antioxidant potential (FRAP). This study included 32 women with BC and 32 controls (CG). ORAC, TEAC, TRAP, and FRAP were significantly lower in BC than in CG. During follow-up, only ORAC increased significantly at T 2 compared to T 1 . A weak positive correlation was found between dTAC (VCE) and serum TAC levels at T 2 (rho = 0.371, p  = 0.036). The relationship between diet and serum biomarkers was not significant. Multicenter prospective studies on different age groups are needed to understand the association between diet and serum biomarkers levels in patients with BC.

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib., Methods: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients., Results: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group., Conclusion: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ibrutinib is a Bruton tyrosine kinase inhibitor used in the treatment of chronic lymphocytic leukemia (CLL). Panitumumab, an mAb for epidermal growth factor receptor, is used in the treatment of metastatic colorectal cancer (CRC). We wanted to present our case where we used ibrutinib and panitumumab in combination in a patient with metachronous CLL and CRC. A 58-year-old male patient with a diagnosis of CLL was receiving ibrutinib treatment and primary rectal cancer was detected. FOLFOX + panitumumab were started when metastasis was detected in the lung after neoadjuvant chemoradiotherapy for rectal cancer. The patients used ibrutinib and panitumumab in combination. There was no cumulative or unexpected toxicity due to the combination of both antineoplastic agents. The most important point to be considered in the use of combined drugs is the evaluation of drug-drug interactions. Toxic effects of the combination of ibrutinib and cetuximab have been reported in a patient with metastatic CRC. We used ibrutinib together with panitumumab in our case and we did not encounter any cumulative or unexpected side effects during the treatment., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic giant cell tumors (PGCTs), undifferentiated pancreatic carcinoma are rare tumors of the pancreas. PGCTs consist of osteoclastic, pleomorphic and mixed variants. PGCT is usually diagnosed at an advanced stage. PGCT has a worse prognosis than pancreatic ductal adenocarcinoma. Although surgery can be curative, there is no standard treatment approach for advanced PGCT. We present a case of PGCT that is resistant to standard therapy and progresses in a short time., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Leukocytoclastic vasculitis is a histopathological term describing vasculitis in which the inflammatory infiltrate in small vessels consists of neutrophils. Although FLOT is given perioperatively in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma, it has recently become a popular treatment option for metastatic cancers. In this case report, we present a case of FLOT-induced LCV., Case Report: We present a 52-year-old patient with metastatic gastric adenocarcinoma treated with FLOT. The patient developed necrotizing vasculitis in the lower extremity after 5 cycles of FLOT., Management & Outcome: After discontinuation of the FLOT regimen, the necrotizing morbid LCV gradually regressed with steroid therapy., Discussion: To the best of our knowledge, our case is the first case of LCV that developed after FLOT chemotherapy. The clinical appearance of the patient, occurrence after chemotherapy, erythematous rash developing on bilateral lower extremities, and palpable purpuric vasculitis made us suspect. We found a potential relationship between FLOT and vasculitis according to the Naranjo scale (score 4 + ).

Introduction: Cetuximab, an anti-EGFR monoclonal antibody, often cause skin toxicity, most commonly acneiform rash. We present a rare case of glomerulonephritis associated with cetuximab therapy., Case Report: A 58-year-old male patient recently completed cetuximab-based chemotherapy for metastatic colorectal adenocarcinoma. He presented with acute renal failure, anasarca edema and nephrotic proteinuria. The amount of protein in the 24-h urine test was over 15.6 grams., Management & Outcome: The patient showed a dramatic improvement in renal function shortly after terminated of cetuximab therapy without immunosuppressive therapy., Discussion: Therefore, drugs targeting epidermal growth factor receptor (EGFR) monoclonal antibody were thought to trigger nephrotic syndrome by causing glomerular damage. As a result, physicians using EGFR monoclonal inhibitors should be very careful about renal functions and proteinuria in patients.

Introduction: Trastuzumab emtansine (TDM-1) is an antibody-drug conjugate effective in human epidermal growth factor receptor-2 - expressing advanced breast cancer. Pulmonary complications of TDM-1 are rarely reported. TDM-1-associated interstitial lung disease is referred to as pneumonitis., Case Report: A 47-year-old female patient who underwent modified radical mastectomy and axillary lymph node dissection operations due to a palpable mass in the right breast and axillary region. The patient who had received multiple chemotherapy was last receiving TDM-1 treatment. Fatigue, dyspnea, and tachypnea were detected for the first time on 20 days after the 6 th treatment., Menagement and Outcome: In our case, we first considered metastasis, pneumonia and fungal infection based on radiological findings, but the lack of response to the treatments and the results of the investigations suggested drug-induced pneumonia and steroid treatment was started. Our case had a complete radiological recovery and complete response to sterod therapy. In such cases, it is important to first exclude infections and metastasis. In cases of drug-induced pneumonia, the first treatment option is systemic corticosteroids and generally responded well., Discussion: Unlike other cases of interstitial pneumonia, lung imaging of our case was resembling a metastasis, pneumonia and fungal infection. With increasing use of TDM-1, we will have more experience in both efficacy and complications of TDM-1. Although TDM-1 is a well-tolerated drug, clinicians should be aware of rare pulmonary complications and prepared to respond appropriately.

Purpose: Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity., Methods: We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm., Results: A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use., Conclusion: Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important., Patients and Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method., Results: The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis., Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

This study aimed to compare the dietary intake of carotenoids, tocopherols, ascorbic acid, flavonoids, and dietary total antioxidant capacity (dTAC) and to evaluate relationship of dTAC with serum inflammatory biomarkers in patients with gastrointestinal system (GIS) and non-GIS cancer. In total, 104 adult cancer survivors (52 GIS and 52 non-GIS cancer cases) were included. 24-hour dietary recalls were obtained and dTAC was calculated on the basis of oxygen radical absorption capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant potential (FRAP), and vitamin C equivalents (VCE). Serum C-reactive protein (CRP) level, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were used as inflammatory biomarkers. Routinely analyzed serum CRP, neutrophil, lymphocyte, and platelet levels every day in hospital biochemistry laboratory were obtained from patients' file. There was no significant difference between patients with GIS and non-GIS cancer in terms of dietary intake of carotenoids, tocopherols, and flavonoids. While there was no significant difference between groups in terms of the mean dietary ORAC, TEAC, and FRAP, the mean TRAP of patients with GIS cancer was significantly higher than patients with non-GIS cancer. Serum inflammatory markers (CRP and NLR) were found to have an inverse relationship with dTAC.

Introduction: Regorafenib, a receptor tyrosine kinase inhibitor, is a routinely used targeted agent in the current treatment of patients with refractory metastatic colorectal carcinoma (mCRC). The aims of this study were to detect the presence of bowel wall edema during regorafenib treatment via computed tomography (CT) and to assess the relationship between survival and regorafenib-induced bowel wall edema in patients with mCRC receiving regorafenib., Patients and Methods: We retrospectively evaluated the presence of bowel wall edema on CT of 25 mCRC patients who received regorafenib and analyzed its relationship with progression free survival (PFS) and overall survival (OS)., Results: Among the 25 patients, 25 had small bowel wall edema (SBWE) and 14 had large bowel wall edema (LBWE) on at least one CT examination. The median SBWE value was 4.85 milimeters (mm). Of the 25 patients, 14 had SBWE ≤4.85 mm and 11 had SBWE >4.85 mm. Regorafenib intolerance was significantly higher at SBWE >4.85 mm patients (p = 0.03). The median PFS was 4.6 months (95% CI: 2.4-6.8) and median OS was 9.3 months (95% CI: 3.1-15.4). Median PFS and OS were shorter in patients with SBWE > 4.85 mm than in those with ≤4.85 mm, but not statistically significant (median PFS: 3.9 vs 4.6 months, p: 0.523; median OS: 5.6 vs 9.3 months, p: 0.977)., Conclusions: Regorafenib caused SBWE in patients with mCRC. Patients who developed more SBWE had a higher regorafenib intolerance and a shorter survival. Further studies are needed to confirm the predictor value of SBWE on the survival outcomes of patients with mCRC receiving regorafenib.

Introduction: Pazopanib is an agent that is being successfully used in soft tissue sarcomas. Some endocrine side effects may develop during pazopanib treatment. Here, we presented a case diagnosed with secondary adrenal insufficiency while being investigated for etiology of hypoglycemia which developed after pazopanib., Case Report: A 69-year-old male patient was operated in June 2019 due to a lung mass 26 × 18 × 10 cm in size. Pathological diagnosis revealed a solitary fibrous tumor with malignant behavior. The patient received three lines of chemotherapy. After pazopanib treatment, a hypoglycemic attack was reported. Management and outcome: Blood cortisol and ACTH (Adrenocorticotropic hormone) levels were not increased at the time of the hypoglycemic attack, and levels of other pituitary hormones were found to be normal. Electrolyte levels were in normal range. Since the counteracting hormone did not reach a sufficient level, it was considered secondary adrenal insufficiency. Hypoglycemic attacks did not occur during follow-up while taking steroid therapy and pazopanib., Discussion: A single case of primary adrenal insufficiency has been reported in the literature. We here present a case who developed hypoglycemia after pazopanib and was diagnosed with drug-associated secondary adrenal insufficiency. When hypoglycemia develops during pazopanib treatment, we must be aware of adrenal insufficiency.

Purpose: In this study, we looked for whether treatment-induced rash predicts treatment efficacy in patients with recurrent/metastatic HNSCC treated with Cetuximab and chemotherapy., Methods: Patients who were treated with platinum-based chemotherapy and cetuximab for the first line treatment of recurrent/metastatic HNSCC were recruited. Presence of rash, hypomagnesemia, hypopotassemia, anemia, neutropenia, thrombocytopenia during treatment and treatment response, date of progression, date of last visit and death were recorded., Results: A total of 138 patients' data were available for analysis. Any grade of rash was detected in 57 (44.5%) of the patients. The incidence of rash was significantly higher in patients with objective response than in patients with disease progression (%56.8 vs %14.3, p < 0.001). Progression free survival was 7.06 months (4.98-9.15) in patients treated with cetuximab and chemotherapy as first line treatment. In the multivariate analysis; rash was significantly correlated with longer PFS (HR 2.136; 95% CI 1.067-4.278; p = 0.032). Progression free survival was 9.65 months in patients who experienced rash, and 6.02 months in patients without rash, (p = 0.019, log-rank test). Overall survival was 11.24 months (9.65-12.82). In multivariate analysis, the survival of patients with rash was significantly longer than patients without rash (HR 1.954; 95% CI 1.162-3.285; p = 0.012). Overall survival was 15.08 months in patients who experienced rash, and 8.61 months in patients without rash (p = 0.05, log-rank test)., Conclusion: Cetuximab-induced rash is associated with better ORR and longer PFS and OS in patients with recurrent/metastatic HNSCC treated with Cetuximab and platinum-based chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma., Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma., Design, Setting, and Participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ., Outcome Measurements and Statistical Analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS., Results and Limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies., Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials., Patient Summary: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab., Patients and Methods: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p  < 0.1), and then included a final model of p  < 0.05., Results: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis., Conclusions: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer., (© 2021. Japan Society of Clinical Oncology.)

Introduction: Sweet Syndrome, also known as acute febrile neutrophilic dermatosis, is a rare inflammatory disease characterized by the sudden emergence of painful, edematous, and erythematous papules, plaques, or nodules on the skin, which usually fully responsive to systemic corticosteroids. Skin lesions are often accompanied by fever and leukocytosis. Here we present a case of Sweet Syndrome caused by pemetrexed in metastatic lung adenocarcinoma., Case Report: A 52-year-old patient with metastatic lung adenocarcinoma received multiple lines of chemotherapy. The patient presented with extensive skin lesions after performing of pemetrexed chemotherapy. He had a fever and elevations in blood levels of C-reactive protein (CRP), sedimentation, leucocytes, and neutrophils. Neutrophil predominant perivascular and interstitial dermatitis, focal micropustule formation, and severe neutrophilic dermatosis were reported in skin biopsy. Topical steroid and oral antihistamine treatment were started as initial treatment. Discussion and conclusions: Cutaneous side effects related to pemetrexed are often reported as 'skin rash,' which is a non-specific term. Therefore, the diagnosis of Sweet Syndrome must be confirmed by skin biopsy. It is essential to exclude the presence of an infection and medication history. Recovery in drug-induced Sweet Syndrome occurs after the drug that caused it was discontinued. Systemic corticosteroids are the first-line treatment for most cases.

Background: Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions., Methods: For this Meta-analysis, we searched PubMed, Science of Web, "Clinicaltrials.gov" and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted., Results: A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naïve (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naïve and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively)., Conclusion: Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.

Background: Vaginal metastasis should be kept in mind when evaluating the staging tests of all cancers, especially endometrial cancer., Case Presentation: We present four patients with vaginal recurrence who recently applied to our clinic. Three cases were of endometrial cancer and one case of rectal cancer. All patients presented with vaginal bleeding., Conclusion: Standard treatment for vaginal metastasis has not yet been established. Therapeutic options for vaginal metastasis-separately or in combination-are surgical resection, radiotherapy, and chemotherapy.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) may frequently occur in patients receiving oxaliplatin-based treatment. The aim of the present parallel-group, randomized, controlled pilot trial was to investigate the effect of henna on CIPN in women receiving oxaliplatin-based treatment., Method: Sixty female patients receiving oxaliplatin-based treatment were randomly divided into two groups, i.e., one intervention group (n = 30) where henna was applied topically and one control group (n = 30) that received routine treatment and care. Women in the intervention group were provided a pack of henna prepared by the investigators following each treatment course (2nd, 3rd, and 4th courses) and were instructed to apply the henna on their palms, fingers, and soles. The chemotherapy-induced peripheral neuropathy assessment tool (CIPNAT) was completed by women subsequent to the 2nd (baseline), 3rd, and 4th courses of treatment., Results: The intragroup assessment performed for the intervention group revealed that the total CIPNAT score significantly declined in the intervention group (p < 0.05). The score changes by time in the intervention and control groups were in favour of the intervention group, and the effect size for group × time interaction was η 2  = 0.169. Similarly, regarding the symptoms intervention section of the tool, a positive change by time in the intervention group was observed, and the effect size concerning this change was large, i.e., η 2  = 0.284., Conclusions: The present study results showed that henna application on hands and feet has a beneficial effect on peripheral neuropathy. Applying henna is a promising approach in CIPN management., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Soft tissue sarcomas are a heterogeneous and rare group of cancers with a short median overall survival despite the chemotherapy. Pazopanib has approval for the treatment of advanced soft tissue sarcoma. We aimed to investigate the clinical outcomes of Turkish patients with advanced soft tissue sarcoma who received pazopanib., Patients and Methods: This was a retrospective study. The inclusion criteria were: ≥18 years of age, having histologically proven advanced soft tissue sarcoma and receiving pazopanib at least one day., Results: A total of 79 patients were assessed in this study. The median age was 49.6 years. The average dose intensity of pazopanib was 767 mg (400-800). The median duration of pazopanib treatment was 6.11 months. Fourteen patients (17.7%) used pazopanib at first line for advanced soft tissue sarcomas. The most common cause of discontinuation of pazopanib was the progression of the disease (89.6%). Pazopanib was well tolerated. The most common grade ≥3 side effect was anemia. The most common grade ≤2 side effects were anemia and hyperbilirubinemia. The median progression-free survival, overall survival, and follow-up were 3.97 months, 11.40 months, and 32.72 months, respectively. Female gender, good performance status, and the presence of pazopanib-induced hypothyroidism were associated with longer progression-free survival. Also, good performance status and being a responder to first-line treatment were associated with longer overall survival., Conclusions: We showed that pazopanib was well tolerated and had clinical benefit in patients with advanced soft tissue sarcoma in a Turkish cohort. This is the first study that suggests pazopanib-induced hypothyroidism may act as a predictive marker for better outcomes in patients with advanced soft tissue sarcoma.

Background: Checkpoint inhibitors (CPIs) have improved survival compared to chemotherapy alone in advanced nonsmall-cell lung cancer (NSCLC). This article aims to compare indirect evidence and rank the effect of different CPIs in this setting., Materials and Methods: In this network meta-analysis, we searched for trials comparing CPIs in advanced NSCLC. Figures for survival endpoints were extracted. In addition, a network meta-regression analysis was carried out., Results: A total of 9220 patients from 16 trials were included in the analysis. In the first-line setting, for the overall survival endpoint, the chemotherapy + Pembrolizumab combination had the highest effectivity rank probability as compared to chemotherapy (hazard ratio = 0.788, 95% credential interval = 0.728-0.855). For the second-line setting, and also for the efficacy in terms of progression-free survival, various CPIs and their combinations were ranked., Conclusion: Some degree of differences in terms of efficacy exists between different types, dosages, settings, and combinations of CPI. We quantify these differences to guide clinical practice., Competing Interests: None

Purpose: The purpose of this study was to investigate whether obesity affects survival in metastatic colorectal cancer (mCRC) patients treated with bevacizumab combined with chemotherapy., Methods: A total of 563 patients with mCRC who had received first-line chemotherapy in combination with bevacizumab were studied. Patients were grouped as obese (BMI levels > 30) or non-obese (BMI levels < 30). Progression-free survival (PFS) and overall survival (OS) were analyzed. Primary tumor location was also investigated in terms of PFS and OS., Results: The median age of the patients was 59 years. The non-obese group had longer PFS than the obese group (P = 0.030). The 2-year survival rate of the non-obese group was also significantly higher (P = 0.036). The median PFS of non-obese patients was significantly longer in Kras wild-type patients (10.1 vs. 8.1 months, P = 0.010). Among patients with left-sided primary tumor location, median PFS and OS were significantly higher in the non-obese group (PFS non-obese, 11.5 months; obese, 8.8 months; P = 0.002) (OS non-obese, 29.4 months; obese, 21.4 months; P = 0.026)., Conclusions: Efficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.