Cabozantinib-induced heart failure.

INTRODUCTION: Cabozantinib is a multikinase inhibitor agent used in the treatment of hepatocellular, renal, and thyroid cancers. The development of heart failure after cabozantinib initiation is an extremely rare side effect, with only four case reports published in the literature. We describe a case of cabozantinib-induced cardiac failure in a patient with thyroid cancer refractory to standard treatment. CASE REPORT: Fifty-seven-year-old woman had no history of cardiovascular disease. Echocardiography prior to chemotherapy revealed normal cardiac function. However, she developed pretibial edema and shortness of breath after 2 months of cabozantinib treatment. Ejection fraction was found to be 30% in the echocardiography of the patient, and global hypokinesia was detected in cardiac functions. MANAGEMENT AND OUTCOME: Cabozantinib treatment of the patient was discontinued. After discontinuation of treatment, the patient's cardiac functions did not return to normal. Heart failure due to cabozantinib treatment was thought to be permanent. DISCUSSION: There are only four cases on this subject in the literature. Although the use of cabozantinib rarely causes heart failure, this side effect can have extremely serious consequences. Even if it is a rare condition, cardiological evaluations should be performed before and after cabozantinib therapy because it can be reversible after discontinuation of the treatment.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study.

OBJECTIVE: To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). METHODS: A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. RESULTS: The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. CONCLUSION: In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.

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.

Toxic hepatitis in metastatic breast cancer patient using ribociclib and denosumab.

INTRODUCTION: Hepatotoxicity is observed due to cyclin-dependent kinase (CDK4/6) inhibitors used to treat hormone receptor-positive metastatic breast cancer. However, it should not be ignored that denosumab may be hepatotoxic, although it is rare. CASE REPORT: A 73-year-old female patient with breast cancer with axillary lymph node, adrenal gland and bone metastases was started on ribociclib letrozole and denosumab treatment. Ribociclib treatment was discontinued due to grade 4 hepatotoxicity during treatment, but liver function tests did not decrease. After discontinuation of denosumab treatment, alanine aminotransferase and aspartate aminotransferase values regressed to baseline values. MANAGEMENT AND OUTCOME: Despite the discontinuation of ribociclib treatment, other causes of liver toxicity were investigated due to persistence of hepatic transaminases and elevation. Autoimmune hepatitis markers were negative. Hepatobiliary USG did not reveal any pathological findings except hepatosteatosis. Liver biopsy was performed to determine the etiology. Pathology result was compatible with acute hepatocellular damage (in favor of toxic hepatitis). A decrease in liver values was detected after discontinuation of denosumab treatment. DISCUSSION: Although cases with improvement in liver enzymes have been reported after discontinuation of ribociclib, no improvement in hepatotoxicity was observed in our case. Since the liver biopsy was toxic hepatitis, it was thought that other drugs used by the patient might cause this toxicity, and a significant decrease was observed in liver values after discontinuation of denosumab. Denosumab-induced liver toxicity is very rare, and there are only a limited number of cases in the literature.

Clinicopathological and survival features of neuroendocrine tumors: A retrospective analysis of 153 cases, our current remarks on a heterogeneous tumor group, and still unmet future expectations.

Objective: Neuroendocrine neoplasms (NENs) originate from the diffuse neuroendocrine cell system and constitute a heterogeneous group of tumors exhibiting diverse clinical and biological characteristics. NENs include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). In the present study, we performed a retrospective analysis of patients diagnosed with NET to evaluate clinicopathological characteristics, treatment and outcomes. Material and Methods: Data from 153 patients diagnosed with NET who were treated and followed up at three tertiary care centers from November 2002 to June 2021 were retrospectively evaluated. Clinicopathological and prognostic factors, treatment modalities and survival data were analyzed. Kaplan-Meier analysis was used to assess survival data and comparisons were performed using the logrank test. Results: Median age (IQR) was 53 (18-80) years. 85.6% of the patients had gastro-entero-pancreatic (GEP)-NET. The primary tumor was resected in 95 patients (62.1%) and metastasectomy were performed in 22 patients (14.4%). Seventy-eight patients received systemic therapy for metastatic disease. Patients were followed up for a median of 22 (IQR = 33.8) months. The estimated one-year and three-year survival rate was 89.8% and 74.4%, respectively. Median progression-free survival (PFS) were 10.1, 8.5, and 4.2 months after first-, second- and third-line therapy, respectively. Conclusion: The number of systemic treatment options and diagnostic tools for NETs has significantly improved in the last few years. NET classification, which treatment will be more appropriate for which group of patients, the molecular basis of this disease and the development of treatment strategies are open-ended questions that still need to be investigated.

Does Prognostic Nutritional Index Predict Survival in Operated Papilla Vateri Tumors? A Single-centre Experience.

OBJECTIVE: To determine the PNI's prognostic effect of prognostic nutritional index (PNI)  on operated papilla vateri tumor (PVT) survival. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey, from April 2003 to December 2020. METHODOLOGY: One hundred and eighty-two patients diagnosed with PVT were retrospectively screened. One hundred and twenty-six non-metastatic patients, who met the inclusion criteria and underwent curative surgery. PNIs were calculated using preoperative albumin and lymphocyte values and the cut-off value was taken and the two groups were compared in terms of overall survival. RESULTS: The median age of the patients included in the study was 61 (36-88) years; 59.5% were males. The cut-off value was obtained using ROC-curves for the preoperative PNI values of 126 patients who underwent curative surgery. Patients were divided into two groups as PNI ≥38 and PNI <38. While median overall survival could not be reached in the group with high PNI, it was 39.3 months in the group with low PNI (p <0.001). In the multivariate cox analysis, PNI elevation was found to be an independent prognostic factor associated with a good prognosis (hazard ratio: 0.18, 95% CI: 0.07-0.48, p <0.001). CONCLUSION: In patients with papilla vater tumors, undergoing curative surgery, PNI can play a role as an independent marker in predicting prognosis. Key Words: Prognostic nutritional index, Papilla vater tumor, Prognosis, Survival.

Is there any correlation among MKK4 (mitogen-activated protein kinase kinase 4) expression, clinicopathological features, and KRAS/NRAS mutation in colorectal cancer.

BACKGROUND: We aimed to evaluate the correlation between MKK4 expression and clinicopathological features, KRAS/NRAS mutation in colorectal cancer. METHODS: MKK4 expression was assessed by immunoreactivity score (IRS). Staining intensity(SI) and percentage of positively stained cells (PP) were used for IRS (IRS = SI×PP). Cutoffs were explored with ROC analysis. Patients were grouped as WIR ('weak immunoreactive'; IRS:0-2) and SIR ('strong immunoreactive'; IRS: >3). RESULTS: We enrolled 95 patients. 63.2% had metastasis. Median follow-up was 31.4 months. KRAS/NRAS mutation rate was 45.2%. Median values for OS, DFS, and PFS were as 31.6, 17.2, and 10.3 months. WIR group had longer OS (p = 0.03). Recurrence rate was 36.8%. Median DFS was longer for recurrent patients in WIR group (p = 0.055). KRAS or NRAS wild-type patients and those with left-sided tumors in WIR group had longer OS (p = 0.029, p = 0.024, p = 0.03). There was no PFS difference (p: 0.15). In correlation analysis, there was a negative correlation between MKK4 expression and KRAS mutation, NRAS mutation, OS, PFS, DFS (r: -0,06; r: -0,02; r: -0,10; r: -0,06; r: -0,34). Only the correlation for MKK4 expression and DFS was significant (p = 0.04). CONCLUSION: MKK4 expression inversely correlates with survival outcomes. Patients with KRAS/NRAS wild-type, left-sided tumors with WIR had longer OS.

Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer.

BACKGROUND: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. RESULTS: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ≥3.24) and PNI (<49.5 or ≥49.5). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). CONCLUSIONS: NLR (≥3.24) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.