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Introduction: Pembrolizumab is a humanized monoclonal antibody IgG4 programmed cell death protein 1 antagonist, and its use in oncology has been increasing in recent years, providing durable and favorable responses and tolerable toxicity profiles in various types of cancer. We describe a case of pembrolizumab related perforated appendicitis in a patient with stage 3C malignant melanoma (MM). Case report: A 70-year-old male patient who had no known disease was diagnosed with MM as a result of the excision of the mass on his right shoulder. The disease stage was stage 3C (pT4aN1bM0). Subsequently, adjuvant pembrolizumab treatment was started. A few days after the fourth maintenance course, he presented to the emergency department complaining of abdominal pain, nausea and vomiting. Emergency abdominal tomography showed a significant increase in the diameter of the appendix vermiformis, peritoneal thickening and appendiceal wall defects that could be significant in terms of perforation. Management and outcome: The mentioned finding and given the clinical presentation, was attributed to a perporating of the appendix, so the patient was hospitalized in the Department of Surgery and the patient underwent emergency appendectomy. Histological findings were consistent with appendicitis. After a day in the hospital, the abdominal pain subsided, C-reactive protein tended to decrease and the patient was discharged. Discussion: In patients who develop acute abdominal pain with or without diarrhea during immunotherapy, urgent imaging, endoscopic and clinical evaluation should be performed, and bowel perforation, although rare, should be considered as a potential complication of any immunotherapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: In this study, we evaluated the impact of seven immune indexes on treatment response and survival outcomes in advanced non-small-cell lung cancer (NSCLC) patients receiving second-line and subsequent nivolumab treatment under real-life conditions. Materials and Methods: The pan-immune inflammation value (PIV), systemic immune inflammation value (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), and prognostic nutritional index (PNI) were calculated. All immune indexes were classified as low and high based on cut-off values. Kaplan–Meier and Cox hazard models were used for survival analysis. Results: The median follow-up was 22.0 months (6.0–96.0). The median overall survival (OS) was 30.0 months and the median progression-free survival (PFS) was 7.0 months. In the univariate analysis, comorbidity (p = 0.03) and nivolumab use for more than eight cycles (p < 0.0001) were associated with an increase in PFS, while smoking history (p < 0.005) and d-NLR (p < 0.05) were more effective regarding OS. Patients who received more than eight cycles of nivolumab had longer median PFS (4 vs. 19 months, p < 0.001) and OS (23 vs. 43 months, p < 0.001). We found longer median OS in the PLR (45.7 vs. 75.4 months; p = 0.05), PIV (53.0 vs. 66.4 months; p = 0.19), SII (50.0 vs. 71.9 vs. months, p = 0.19), and NLR (49.9 vs. 74.55 months, p = 0.10) indexes in nivolumab long-term users (high vs. low groups, respectively). In short-term users of nivolumab, only d-NLR median OS (high vs. low, 19 vs. 75.2 months, p = 0.07) was different. Complete and partial response rates to nivolumab treatment were higher in the PNI-high group (p = 0.04). Conclusions: In these real-life data, we determined that the PLR, PIV, SII, and NLR indexes were effective in the prognosis of patients who received PD1 inhibitor nivolumab for a long time, and the d-NLR index was effective in those who developed progression in a short time. We found that the PNI was effective in patients who responded well to ICI treatment. [ABSTRACT FROM AUTHOR]

Aim: Inflammation-related markers are the factors affecting prognosis in many types of cancer. In this study, we aimed to investigate the relationship between inflammation-related markers, neutrophil-lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) with prognosis of patients with uterine leiomyosarcoma (uLMS). Methods: Patients diagnosed with uLMS were reviewed retrospectively. NLR, PLR, SII, and PNI values were calculated at the diagnosis and before treatment. Totally 35 patients were included in the study. Results: Median overall survival (OS) in the low-NLR (<2.10) group was not reached using Kaplan-Meier analysis, whereas in the high-NLR (≥2.10) group, median OS was 41.6 months (95% CI:25.7 -- 57.4) (p=0.019). Median OS in the low-PLR (<145) group could not be reached using Kaplan-Meier analysis, whereas, in the high-PLR (≥145) group, the median OS was 43.0 months (95% CI:21.9 -- 64.1) (p=0.046). The median OS was 107.7 months (confidence interval not reached using Kaplan-Meier analysis) in the low-SII (<806) group, while the median OS was 43.0 months (95% CI:23.7 -- 62.3) in the high-SII (≥806) group (p=0.039). In the low-PNI, (<53.7) group, the median OS was 53.2 months (95% CI:20.8 --90.9), while in the high-PNI (≥53.7) group, the median OS was 41.6 months (0 -- 94.0) (p=0.652). In multivariate analysis, mitotic count and NLR were observed as independent factors affecting prognosis in OS (p=0.012 and p=0.035). Conclusions: NLR≥2.10 is an independent marker showing a poor prognosis in uLMS patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the correlation between MKK4 expression and clinicopathological features, KRAS/NRAS mutation in colorectal cancer. 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). 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). MKK4 expression inversely correlates with survival outcomes. Patients with KRAS/NRAS wild-type, left-sided tumors with WIR had longer OS. [ABSTRACT FROM AUTHOR]