Causes of liver test abnormalities in newly diagnosed cancer patients and the investigation of etiological factors.

OBJECTIVES: In this study, we aimed to investigate the causes of liver test abnormalities in newly diagnosed patients naive to anti-tumoral therapy. METHOD: This study included a total of 490 patients with ALT levels > 5X ULN on liver function tests at the initial presentation to our clinic. Data from 247 (50.4%) patients diagnosed with cancer (cohort A) and 243 (49.6%) patients without cancer (cohort B) were compared with regard to the etiology of liver test abnormalities and the risk factors. RESULTS: The most common etiological factor in cohort A was presence of liver metastasis (31.2%, n = 77). In the comparison of the two groups with regard to etiological factors; the rates of liver metastasis [31.2% vs 0%, (p < 0.001)], drug-induced liver toxicity [30/4% vs 19.8%, (p = 0.007)], pancreaticobiliary pathology [21.5% vs 14%, (p = 0.03)] and chronic viral hepatitis [14.2% vs 7.4%, (p = 0.02)] were higher in the cohort A. The rate of NAFLD was higher in the cohort B [6.9% vs 42.2% (p < 0.001). CONCLUSION: In our study, the most common cause of liver test abnormalities was the presence of liver metastasis in cohort A and NAFLD in cohort B.

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Comparison of Two Chemotherapy Regimens After First-Line Treatment for HER2-Negative Metastatic Gastric Cancer.

AIM: Metastatic stage gastric cancer is a disease with a poor prognosis and the likelihood of achieving a cure in these patients is low. Treatment response to subsequent-line treatments is poor. We aimed to investigate the effectiveness of the folinic acid, fluorouracil and irinotecan (FOLFIRI) and paclitaxel+carboplatin regimens, which are used in subsequent lines of therapy in advanced-stage gastric cancer. MATERIALS AND METHODS: This study included 40 patients who have metastatic stage gastric cancer and received FOLFIRI or paclitaxel+carboplatin therapy in subsequent lines of therapy between 2017 and 2022. The data of the patients were analyzed retrospectively. RESULTS: At diagnosis median age was 51 (23-88) years. The tumor was localized in the gastroesophageal junction in eight (20%) patients and in other gastric locations in 32 (80%) patients. At diagnosis, 75% (n=30) of the patients presented with the disease in the metastatic stage, while 25% (n=10) presented with stage II-III disease. Regarding the treatments received in the second and further lines of therapy, 18 (45%) patients received paclitaxel+carboplatin and 22 (55%) patients received a FOLFIRI regimen. Of these treatments, 67.5% (n=27) were given as the second line and 32.5% (n=13) were given as third-line therapy. The objective response rate (ORR) was 45.5% in the FOLFIRI arm compared to 16.7% in the paclitaxel+carboplatin arm (p=0.05). Both treatment arms had a median progression-free survival (PFS) of three months (p=0.82). The median overall survival (OS) time was seven months in the FOLFIRI arm compared to eight months in the paclitaxel+carboplatin arm (p=0.71). Side effects were similar between both treatment arms. CONCLUSION: This study determined that FOLFIRI and paclitaxel+carboplatin treatments have similar OS, PFS, and side effect profiles in subsequent line treatment of gastric cancer. The FOLFIRI treatment regimen yielded a higher ORR.

Comparison of the Efficacy and Safety of 3 Months of CAPOX Followed by 3 Months of Capecitabine and 6 Months of CAPOX/FOLFOX in the Adjuvant Treatment of Low-Risk Stage III Colon Cancer Treated Surgically.

INTRODUCTION: In the adjuvant treatment of low-risk stage III colon cancer treated surgically, 3 months of CAPOX followed by 3 months of capecitabine is not a common clinical practice. Since there are no data on this practice in the literature, we have no idea how often it is used. However, it should be noted that this application is used in some centers due to the cumulative neurotoxicity of oxaliplatin but there are insufficient data in the literature on its efficacy. METHODS: The data of patients with colon cancer treated surgically who were followed up in 12 different oncology centers in Turkey between November 2004 and June 2022 were analyzed retrospectively. RESULTS: The study included 194 patients. The treatment arms were as follows: 3 months of CAPOX followed by 3 months of capecitabine = arm A and CAPOX/FOLFOX (6 months) = arm B. There were 78 patients (40.2%) in arm A and 116 patients (59.8%) in arm B. The median age and sex distribution were similar between the treatment arms. The median follow-up period of all patients was 34.4 months (95% confidence interval, 29.1-39.7). When arm A was compared with arm B, 3-year disease-free survival (DFS) was 75.3% versus 88.4% and 5-year DFS was 75.3% versus 82.8%, respectively. There were similar DFS outcomes between the treatment arms (p = 0.09). Rates of any grade of neuropathy were numerically lower in arm A, but the difference between the treatment arms was not statistically significant (51.3% vs. 56.9%; p = 0.44). The frequency of neutropenia was similar between the treatment arms. CONCLUSION: In this study, the efficacy and safety of the 3 months of CAPOX followed by 3 months of capecitabine chemotherapy regimen in the adjuvant treatment of low-risk stage III colon cancer treated surgically were proven. This result may also support the discontinuation of oxaliplatin at 3 months while continuing fluoropyrimidines, which is a common clinical practice but lacks sufficient data.

Prognostic factors and the prognostic role of inflammation indices in malignant pleural mesothelioma.

Background: In this study, we aimed to investigate the prognostic factors of malignant pleural mesothelioma and the prognostic value of inflammation indices in malignant pleural mesothelioma. Methods: Between January 2002 and December 2019, a total of 132 patients (74 males, 58 females; mean age: 55 years; range, 31 to 79 years) diagnosed with malignant pleural mesothelioma were retrospectively analyzed. Patients" demographic data and laboratory results were recorded. The prognostic value of the following five inflammation indices was evaluated: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, C-reactive protein/albumin ratio, and prognostic nutritional index. Results: Of all patients, 81% (n=107) were aged 65 or older and 61.4% (n=81) had an epithelioid histology. Of 12 variables examined in the multivariate analysis for their relationship with survival, age ≥65 years, non-epithelioid subtype, and prognostic nutritional index <40 were found to be poor prognostic factors. Based on the score constructed from these factors, the good prognostic group (score 0-1) had a median overall survival of 21 months and a one-year survival rate of 77.9%, while the poor prognostic group (score 2-3) had a median overall survival of nine months and a one-year survival rate of 29.7%. Conclusion: Our study results indicate that age ≥65 years, prognostic nutritional index <40, and non-epithelioid histological subtype are poor prognostic factors of malignant pleural mesothelioma.

Neoadjuvant Therapy and Factors Influencing Survival in Locally Advanced Non-Small Cell Lung Cancer.

AIM: We aimed to investigate the effectiveness of neoadjuvant therapy (NAT) and clinicopathological characteristics in locally advanced non-small cell lung cancer (NSCLC) (IIIA-IIIB), as well as the influence of the post-NAT treatment modalities on survival. MATERIALS AND METHODS: This study included patients who presented to the Dicle University Medical Oncology Clinic and received NAT for a diagnosis of locally advanced NSCLC between 2004 and 2020. Clinicopathological and radiological data of the 57 patients whose data could be retrieved from the hospital archive system were retrospectively reviewed. Patients' overall survival (OS) and failure-free survival (FFS) times and the factors influencing these times were evaluated. RESULTS: This study included a total of 57 patients consisting of five (8.8%) females and 52 (91.2%) males. The median patient age at diagnosis was 58 (30-75) years. All patients had received four courses of chemotherapy during the neoadjuvant period. When the factors influencing OS were evaluated, the post-NAT modality was found to have a statistically significant effect on survival. FFS times were 12, 13, and 16 months in the chemotherapy, chemoradiotherapy, and surgery arms, respectively (log-rank p=0.035). FFS was longer in those who underwent surgery (Hazard ratio (HR): 0.33, 95 % CI: 0.14-0.77, (p=0.01)). OS times were 20, 21, and 55 months in the chemotherapy, chemoradiotherapy, and surgery arms, respectively (log-rank p=0.05). OS was longer in the arm undergoing surgery compared to the other arms (HR: 0.36, 95% CI: 0.14-0.87, (p=0.02)). Five-year survival rates for the chemotherapy, chemoradiotherapy, and surgery arms were 14.3%, 21.4%, and 40%, respectively. CONCLUSIONS: This study shows that achieving an operable status is the most important indicator of survival and that patients undergoing surgery have a marked advantage in OS and FFS compared with patients receiving chemoradiotherapy or palliative chemotherapy.

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

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

18 F-FDG PET/CT parameters for prediction of response to neoadjuvant therapy and prognosis in rectal cancer.

OBJECTIVE: This study aims to investigate the role of F-18 fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) parameters in the prediction of treatment response and the prognosis in locally advanced rectal cancer. METHODS: We investigated the relationship of 18F-FDG PET/CT parameters [rectal metabolic tumor volume (MTV), rectal total lesion glycolysis (TLG), rectal standard uptake value (SUV) max, rectal highest peak SUV, lymph node MTV, lymph node TLG, lymph node highest peak SUV] with the pathological response and disease-free survival (DFS) in 60 patients who received neoadjuvant therapy for a diagnosis of locally advanced rectal cancer. Patients with a total score of 0 were assigned to the low-risk group, patients with a score of 1 were assigned to the intermediate-risk group and patients with a score of 2 were assigned to the high-risk group. RESULTS: The multivariate analysis revealed that, from baseline PET CT parameters, lymph node highest peak SUV strongly predicted the pathological response at a cutoff value of 2.23. DFS was predicted by the lymph node highest peak SUV at a cutoff value of 3.13 and by the MTV value at a cutoff value of 27 cm 3 . The risk scoring performed with regard to rectal MTV and lymph node highest peak SUV values determined a median DFS of 19 months in patients with a risk score of 2, whereas the median DFS was not reached in patients with risk scores of 0 and 1 (P < 0.001). CONCLUSION: This study determined that rectal MTV and lymph node highest peak SUV predicted the response to neoadjuvant therapy and DFS.

Factors influencing HER2 discordance in nonmetastatic breast cancer and the role of neoadjuvant therapy.

Objective: The rates of and the factors influencing HER2 discordance in patients receiving neoadjuvant therapy for breast cancer are investigated. Methods: This study retrospectively examines the rates of HER2 and hormone receptor discordance between the biopsy and postoperative resection specimens of 400 female early-stage breast cancer patients. Results: 133 (33.3%) patients had received neoadjuvant therapy. The rate of HER2 discordance between biopsy and resection specimens was 1.7% in the control group and 5.3% in the neoadjuvant therapy group (p = 0.018). The rate of HER2 discordance was higher in younger patients and in patients with T1 tumors in the neoadjuvant therapy group. Conclusion: Neoadjuvant therapy, age <40 years and smaller tumor size were independent risk factors for HER2 discordance.

HER2 is an important and targetable molecule in breast cancer. In the early stages of breast cancer, a treatment modality called neoadjuvant therapy, which now includes anti-HER2 therapies, is administered before surgery in order to achieve disease regression and make the patient suitable for a more minor operation. In breast cancer, HER2 status may be positive in the initial biopsy specimen and negative in the surgical specimen. HER2 status plays an important role in treatment decisions. In this study, we investigated the factors causing HER2 status to change in early-stage breast cancer. This study has a retrospective design and includes 400 female patients with early-stage breast cancer. The results of the study identified the factors causing HER2 status to change to negative as receipt of neoadjuvant therapy, small tumor size and younger age.

Evaluation of Factors Predicting the Effectiveness of Regorafenib in the Treatment of Metastatic Colorectal Cancer.

OBJECTIVE: Regorafenib is a multikinase inhibitor, the effectiveness of which was demonstrated in metastatic colorectal cancer. This study aimed to investigate the factors that could predict the effectiveness of regorafenib. MATERIALS AND METHODS: This study retrospectively reviewed the clinical characteristics, tumor characteristics, and previous therapies in 62 patients who presented to our center between 2016 and 2020 and used regorafenib for metastatic colorectal cancer. The effects of the investigated variables on the response obtained with regorafenib use were evaluated. RESULTS: This study included a total of 62 patients diagnosed with metastatic colorectal cancer, of whom 30 (48.4%) were males and 32 (51.6%) were females. Patients' median age at diagnosis was 49 years (18- 68). Regorafenib therapy yielded a disease control rate of 64% [complete response=0, partial response= 14 (28%), and stable disease=18 (36%)]. Objective response was obtained in 28% of patients [complete response=0 and partial response=14 (28%)]. Progression-free survival was 4 months. The evaluation of the effects of patients' age, sex, performance status, previous treatments, metastatic sites, and RAS mutation status on the disease control rate and progression-free survival did not determine any positive or negative effects on progression-free survival. However, left-sided tumors had a positive effect on disease control rate (69.8% vs. 28.6%, P=.029). and previous use of cetuximab had a negative effect on disease control rate [76.5% vs. 37.5% (P=.007)]. CONCLUSION: In our study, tumor localization and previous cetuximab use were found to be correlated with the disease control rate in patients on regorafenib. However, the need for novel biomarkers that will predict the effectiveness of regorafenib in metastatic colorectal cancer treatment persists.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

Predictive and prognostic effect of ABO blood group on immune checkpoint inhibitors.

BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively (p= 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p= 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p= 0.03; 20.0 vs. 7.4 months for OS, respectively, p= 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma.

Successful Dialysis Treatment of Metformin Associated Lactic Acidosis, Report of Two Cases.

INTRODUCTION: Metformin-associated lactic acidosis is rare despite its widespread use. It is often associated with the use of metformin in the presence of chronic kidney disease, but it may also occur in people with normal renal function in the case of acute overdose. CASE REPORT: 20 years old (patient 1) and 37 years old (patient 2) women without any chronic disease took 40 gram (727 mg/ kg) and 60 gram (1200 mg/kg) metformin, respectively; for the suicidal attempt. Deep lactic acidosis was detected in patients. In patient 1, hemodialysis was performed for 4 hours. After the interruption, deep acidosis evolved again and another dialysis session was performed. In patient 2, hemodialysis was performed for 16 hours without any interruption and she did not need any other dialysis session. CONCLUSION: Metformin has a large distribution volume. It is not correct to make a final decision as to how long the dialysis will continue when dialysis begins. Dialysis should be continued without interruption until clinical and laboratory targets are achieved.