Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study.

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.

Epidermal growth factor receptor and programmed cell death-1 expression levels in peripheral T cell subsets of patients with non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non-small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min-max) = 64.03 (45-83); 20 stage I-III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD-1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD-1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC.

Rare case of myelodysplastic syndrome with excess blasts 2 developing after adjuvant chemoradiotherapy for triple-negative breast cancer in a patient with Bloom syndrome.

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/m2) and cyclophosphamide (600 mg/m2) followed by weekly paclitaxel (80 mg/m2) 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/m2) 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.

A simulated trial with reinforcement learning for the efficacy of Irinotecan and Ifosfamide versus Topotecan in relapsed, extensive stage small cell lung cancer.

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.

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab as first-line treatment for metastatic non-small cell lung cancer with high levels of programmed death-ligand 1: a randomized, double-blind phase 2 study.

BACKGROUND: Pembrolizumab is a first-line therapy for certain patients with advanced/metastatic non-small cell lung cancer (NSCLC). Combining pembrolizumab with other immunotherapies may enhance tumor cell killing and clinical outcomes. Epacadostat is a selective inhibitor of indoleamine 2,3-dioxygenase 1, an immuno-regulatory enzyme involved in tryptophan to kynurenine metabolism that inhibits T cell-mediated immune responses. METHODS: In this randomized phase II study, patients with metastatic NSCLC expressing high (≥ 50%) programmed death-ligand 1 (PD-L1) levels received pembrolizumab 200 mg every 21 days plus oral epacadostat 100 mg twice daily (combination) or matching placebo (control). The primary objective was objective response rate (ORR); secondary objectives were progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety/tolerability. RESULTS: 154 patients were randomized (77 per group). Median (range) follow-up was 6.8 months (0.1-11.4) and 7.0 months (0.2-11.9) in the combination and control groups, respectively Confirmed ORR was similar between groups (combination: 32.5%, 95% CI 22.2-44.1; control: 39.0%, 95% CI 28.0-50.8; difference: - 6.5, 95% CI - 21.5 to 8.7; 1-sided P = 0.8000). Median (range) DOR was 6.2 months (1.9 + to 6.5 +) and not reached (1.9 + to 8.6 +) in the combination and control groups, respectively. Although not formally tested, median PFS was 6.7 and 6.2 months for the combination and control groups, respectively, and median OS was not reached in either group. Circulating kynurenine levels increased from C1D1 to C2D1 (P < 0.01) in the control group and decreased from C1D1 to C2D1 (P < 0.01) in the combination group but were not normalized in most patients. The most frequent serious adverse events (AEs) (≥ 2%) were pneumonia (4.0%), anemia (2.7%), atelectasis (2.7%) and pneumonitis (2.7%) in the combination group and pneumonia (3.9%), pneumonitis (2.6%) and hypotension (2.6%) in the control group. Two deaths due to drug-related AEs were reported, both in the control group. CONCLUSIONS: Addition of epacadostat to pembrolizumab therapy for PD-L1-high metastatic NSCLC was generally well tolerated but did not demonstrate an improved therapeutic effect. Evaluating higher doses of epacadostat that normalize kynurenine levels when given in combination with checkpoint inhibitors may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03322540. Registered 10/26/2017.

The effect of concomitant beta-blocker use on survival in patients with metastatic renal cell carcinoma treated with a vascular endothelial growth factor receptor inhibitors in the first line.

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.

The impact of body mass index on the progression-free survival of CDK 4/6 inhibitors in metastatic breast cancer patients.

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/m2, overweight (group 2) 25-29.9 kg/m2 and obese (group 3): ≥30 kg/m2. 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.

[Box: see text].

Lorlatinib experience in a patient with ALK + non-small cell lung cancer on hemodialysis: A case report.

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.

Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer.

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.

Comparison of granisetron and palonosetron in triplet anti-emetic prophylaxis in non-small cell lung cancer patients receiving cisplatin-based highly emetogenic chemotherapy.

INTRODUCTION: We compared the efficacy of first-generation granisetron and second-generation palonosetron in triplet anti-emetic prophylaxis in patients with non-small cell lung cancer (NSCLC) receiving cisplatin-based high emetogenic chemotherapy (HEC). METHODS: This prospective, multicenter, non-randomized, observational study was conducted between June 2018 and December 2021. Patients diagnosed with NSCLC who received triplet anti-emetic prophylactic treatment with aprepitant and dexamethasone plus granisetron or palonosetron before the first cycle of chemotherapy were included in the study. At the end of the first week after chemotherapy, the emesis scale was applied to the patients during the outpatient control. The primary endpoint was complete response (CR) and total control (TC). RESULTS: One hundred twenty-one patients were included in the study. Sixty-one patients were in the granisetron group and 60 patients were in the palonosetron group. CR was higher with granisetron in the acute phase (70.5% vs. 58.3%, p = 0.16; respectively) and higher with palonosetron in the delayed phase (61.7% vs. 55.7%, p = 0.5; respectively), although not statistically significant. The TC rates were also not significantly different between the groups (54.1% vs.57.6%, p = 0.69). CONCLUSIONS: There was no significant difference between granisetron and palonosetron in both acute and delayed control of emesis in NSCLC patients receiving cisplatin-based HEC.

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

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

The Evaluation of Dietary Antioxidant Capacity, Dietary Inflammatory Index and Serum Biomarkers in Breast Cancer: A Prospective Study.

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 (T1), before chemotherapy (T2), at 6th (T3) and 12th months of chemotherapy (T4). Serum tumor necrosis factor alpha, interleukin 1ß, 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 T2 compared to T1. A weak positive correlation was found between dTAC (VCE) and serum TAC levels at T2 (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.

Could the concomitant use of beta blockers with bevacizumab improve survival in metastatic colon cancer?

AIM: Drug-drug interactions are sometimes neglected in oncology practice. Due to drug pharmacokinetic and pharmacodynamic interactions, clinically increased or decreased drug effects and increased or decreased adverse effects may occur. Considering that the concomitant use of these two drugs that affect vascular endothelial growth factor receptor (VEGFR) may cause pharmacological potentiation or additive interaction, we aimed to evaluate the survival outcomes of concomitant use of bevacizumab and beta blockers in patients with metastatic colorectal cancer (mCRC). METHODS: In total, 181 patients with mCRC administered with bevacizumab plus cytotoxic chemotherapy regimen in a first-line setting were divided into two groups: concomitant beta-blocker user and nonuser. RESULTS: The median overall survival (mOS) was 35.9 (95% CI: 27.9-43.9) months in the beta-blocker-using group and 29.6 (95% CI: 27.9-43.9) months in the beta-blocker-non-using group (p = 0.054). The median progression-free survival (mPFS) was 16.1 (95% CI: 12.4-19.9) months in the beta-blocker-using group and 12.8 (95% CI: 10.6-15.0) months in the beta-blocker-non-using group (p = 0.006). The multivariate analysis revealed that beta-blocker use was an independent predictor of mPFS (HR: 0.66, 95% CI: 0.46-0.93, p = 0.018) and mOS (HR: 0.57, 95% CI: 0.36-0.91, p = 0.02). CONCLUSION: This study demonstrated that concomitant usage of beta blockers improved both survival outcomes, irrespective of the kind of beta blocker.

The effect of concomitant use of proton pump inhibitors with CDK 4/6 inhibitors on survival in metastatic breast cancer.

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.

Prognostic biomarkers in metastatic colorectal cancer: delta prognostic nutritional index, delta neutrophil to lymphocyte ratio, and delta platelet to lymphocyte ratio.

BACKGROUND: The aim of this study is to determine the prognostic value of the prognostic nutritional index (PNI), the neutrophil to lymphocyte ratio (NLR), and the platelet to lymphocyte ratio (PLR) and their dynamic changes on survival outcomes in metastatic colorectal cancers (mCRC). METHODS: The data of 199 patients with mCRC were retrospectively analyzed. To evaluate the temporal relation between the PNI, NLR, and PLR values and survival, pre-chemotherapy PNI, NLR, and PLR levels were assessed from peripheral blood cell counts on admission; post-chemotherapy PNI, NLR, and PLR levels were assessed with follow-up blood cell counts within two weeks after chemotherapy; and the difference between pre-chemotherapy PNI, NLR, and PLR levels and post-chemotherapy PNI, NLR, and PLR levels was evaluated as delta PNI, delta NLR, and delta PLR. RESULTS: The median PNI, PLR, and NLR were 39.01, 150.2 and 2.53 before chemotherapy and 38.2, 146.6, and 3.31 after chemotherapy, respectively. The median OS was 23.7 months (95%CI:17.8-29.7) and 28.9 months (95%CI:24.8-33.08) for pre-chemotherapy PNI level < 39.01 vs. PNI level ≥ 39.01, respectively(p = 0.035) The positive delta PNI was significantly higher for OS than the negative delta PNI(p < 0.009). Delta PLR and delta NLR were not significant for OS and PFS(p > 0.05 for all). CONCLUSIONS: The results of this study clearly show that the negative delta PNI to be an independent predictor of poor OS and poor PFS in patients with colon cancer who received first line treatment. In addition, delta NLR and delta PLR were shown not to predict survival outcomes.

Are dietary and serum advanced glycation end-products related to inflammation and oxidation biomarkers in breast cancer patients: a follow-up study.

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 6th month of chemotherapy (T3), and at the 12th 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.

Ribociclib-induced hepatotoxicity.

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.

Dietary Antioxidant Capacity and Serum Inflammatory Biomarkers Levels in Cancer Survivors.

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.

Ibrutinib and panitumumab used in combination safely in a patient with metachronous colorectal cancer and chronic lymphocytic leukemia.

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.

Is pancreatic giant cell tumor resistant to standard chemotherapy?

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.