Investigation of the status of immune checkpoint molecules (PD-L1 and PD-1) in meningiomas by immunohistochemistry.

Background/aim: Meningiomas are the most common primary brain tumors of the central nervous system. Immunotherapy is a promising treatment method applied in many types of cancer. There is no standard and effective medical treatment to reduce recurrence and mortality in cases of incomplete resection of meningiomas and in high-grade cases. In order to investigate medical treatments in addition to surgery and radiotherapy, in this study, the status of immune checkpoint molecules (PD-L1/PD-1), which are the target of immunotherapy, in meningiomas was investigated. Materials and methods: Four hundred two cases of meningioma diagnosed between 2007 and 2020 at our institution were used. New blocks were prepared from the appropriate blocks of the cases using the tissue microarray method. Sections obtained from these blocks were immunohistochemically stained with PD-1 and PD-L1 antibodies. Obtained data were interpreted with statistical analysis. Results: Expression of PD-L1 was observed in 28.4% of meningiomas. Staining rates are higher in high-grade tumors. The staining rate of PD-L1 in the tumor increased significantly with pattern loss. PD-L1 expression in immune cells is 19.9%. Immune cell expression and the number of expressing immune cells correlate with spontaneous necrosis. Immune cell expression and the number of expressing immune cells are increased in high-grade meningiomas. PD-1 expression in immune cells is 9.0%, and this correlates with brain invasion. Conclusions: With these data, it was observed that the expression of immune checkpoint molecules PD-L1 and PD-1 increased especially in high-grade meningiomas. It may be the subject of research that these molecules may be targets of immunotherapy in the treatment of meningiomas.

Comparison of the efficacy of sunitinib and pazopanib in patients with advanced non-clear renal cell carcinoma.

Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib.

Pazopanib and sunitinib treatments show similar progression free survival, overall survival and objective response rate.IMDC risk group, liver metastasis, sarcomatoid component and de novo metastatic disease were determined as prognostic factors.

Complete and rapid response with the combination of immunotherapy and chemotherapy in a young adult patient with microsatellite instability-high metastatic gastric cancer.

ABSTRACT: Gastric cancer (GC) is an aggressive malignancy; 5.0% of GC patients are diagnosed before the age of 40. These patients are more aggressive and advanced stage at the diagnosis. Microsatellite instability-high (MSI-H) status is usually seen in relatively older patients. We report a 31-year-old male patient presenting with an intra-abdominal mass and spleen lesions that radiologically mimic a gastrointestinal stromal tumor (GIST). He underwent surgery. Histological examination revealed poorly differentiated adenocarcinoma starting from the deep gastric mucosa. After surgery, rapidly progressive disease was observed. The patient with MSI-H and combined positive score (CPS) of 65% was treated with a combination of immunotherapy and chemotherapy; complete response was observed in approximately 3 months. This is a very rare GC case in young adult age with MSI-H status and responds to treatment in a short time. Predictive markers for immunotherapy efficacy are still being discussed; this case supports the predictive role of high CPS score and MSI-H phenotype in demonstrating treatment efficacy.

Pathological complete response and associated factors in breast cancer after neoadjuvant chemotherapy: A retrospective study.

Objectives: This study aimed to determine clinical and pathological factors that identify a pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Material and Methods: A retrospective, single-center study was conducted in women over the age of 18 who had been diagnosed with pathologically confirmed invasive breast cancer and who had received NAC between July 2016 and October 2021. Patient demographics, clinical, radiological, treatment, and pathological data were reviewed from the electronic hospital records. The primary outcome of interest was pCR, defined as the absence of residual invasive breast cancer in both the breast and axillary lymph nodes. Multivariable logistic regression analysis was used to identify factors associated with pCR. Results: A total of 119 patients were included in the analysis. The distribution of age was 54.5 ± 11.5 years. pCR was observed in 33 (27.7%) patients. pCR for breast tissue was observed in 43 (36.1%) patients. There was no statistically significant relation between the clinical stage and pCR. Age, age at first labor, extent of disease in the breast, NAC completeness, clinical tumor size (cT) stage, clinical lymph node (cN) stage, and molecular subtype were analyzed in a multivariable model. Analysis showed that molecular subtype was the only independent factor related to pCR. pCR rates across molecular subtypes were: 8.7% in luminal-A, 10.8% in luminal-B, 54.5% in human epidermal growth factor receptor 2 (HER-2)-positive, 42.4% in luminal-B (HER-2 positive) and 46.7% in triple-negative. There was no statistically significant difference between luminal-A and luminal-B subgroups (odds ratio 1.15, 95% confidence interval, 0.19-9.35, p= 0.881). Despite the limited number of patients in HER2-positive and triple-negative groups, both demonstrated statistically significant higher odds compared to reference group. Conclusion: The presented study underscores the relevance of molecular subtypes in determining the response to neoadjuvant chemotherapy in breast cancer patients. Particularly HER2-positive and triple-negative subtypes may demonstrate more favorable response rates.

Investigation of the Status of Immune Checkpoint Molecules in Meningiomas by Immunohistochemistry.

AIM: To investigate the status of immune checkpoint molecules (CTLA-4 and TIM-3) in meningiomas and thus contribute to the development of new personalized treatment strategies. MATERIAL AND METHODS: We utilized 402 cases of meningioma for this study. New blocks were prepared using the tissue microarray method, and sections obtained from these blocks were immunohistochemically stained with CTLA-4 and TIM-3 antibodies. Subsequently, statistical analysis were performed. RESULTS: Our findings revealed that CTLA-4 expression were observed in 25.1% of meningiomas. CTLA-4 expression and the number of expressing lymphocytes were found to be significantly higher in high-grade tumors and in those with brain invasion. Meningiomas with staining of immune cells with TIM-3 are 3.5%, and the tumor grade was correlated with the number of immune cells expressing TIM-3. CONCLUSION: Immune checkpoint molecules (CTLA-4 and TIM-3) with varying levels of expression can serve as prognostic and predictive biomarkers, as well as important targets for therapy. Drugs developed for CTLA-4 and TIM-3 molecules may prove to be more effective in treating meningiomas with high-grade, brain-invading, spontaneous necrosis, and macronucleolus.

Arterial Stiffness May Predict Subsequent Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Patients.

Cancer therapy-related cardiac dysfunction (CTRCD) is still a serious problem. Existing risk scores are insufficient for risk classification, especially in low and medium-risk patients. This study aims to evaluate if arterial stiffness (AS) measurement, which is associated with most of the known risk factors, can be a useful parameter for predicting subsequent CTRCD in patients with breast cancer (BC). Patients with BC were included in the study. All patients' AS parameters such as pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), and echocardiographic parameters were obtained before treatment. During treatment, echocardiographic follow-up with routine parameters and left ventricle global longitudinal strain (LVGLS) were measured. Patients were evaluated on whether CTRCD occurred or not. A total of 67 patients were analyzed. The mean age of the study population was 54.9 ± 11 years. Baseline characteristics were similar except for age. No CTRCD diagnosis was obtained according to left ventricle ejection fraction (LVEF) reduction, but 18 patients (26.8%) developed CTRCD regarding the decline in LVGLS. Left ventricle hypertrophy and diastolic dysfunction were more frequent in patients with CTRCD (p = 0.016 and p = 0.015, respectively). PWV, AIx, and AP as AS parameters were significantly higher in patients with CTRCD, but Alx@75 were not (p = 0.005, p = 0.034, p = 0.008, p = 0.077, respectively). A positive correlation between PWV and a decreased percent in LVGS (R = 0.607, p < 0.001) was observed. ROC curve analyses revealed an AUC of 0.747 (p = 0.02, 95% CI 0.632-0.832) for PWV. A PWV value of 9.2 m/s predicted CTRCD with 94% sensitivity and 73% specificity. AS measurement may be useful for predicting CTRCD in patients with low to medium-risk BC.

Factors Affecting the Efficacy of Regorafenib in Metastatic Colorectal Cancer: Is Tumour Sidedness Important?

OBJECTIVE: To investigate the outcomes of regorafenib treatment in refractory metastatic colorectal cancer (mCRC) patients by primary tumour sidedness, the effects of previously targeted therapies, RAS status and inflammatory markers. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey, between January 2012 and September 2020. METHODOLOGY: Clinical data of 102 mCRC patients treated with regorafenib were compared according to the right and left colon subgroups, in terms of factors affecting outcomes of regorafenib treatment. Kaplan-Meier method was used to identify factors associated with the overall survival. RESULTS: Disease control rate (DCR) with regorafenib were similar in both right and left-sided colon tumours (60% vs. 61%, respectively, p>0.99). The median overall survival (OS) was 6.6 months in patients with right-sided colon cancers and 10.1 months in patients with left-sided colon cancers, but it was not significant (p=0.238). When evaluating by RAS status, there was an increase in favour of the right-sided mCRC in progression-free survival and OS, without statistical significance. In multivariate analysis, the patients with metastatic sites <3 and the number of prior systemic therapies ≤3 line had significantly higher survival. CONCLUSION: The tumour burden affected the response to regorafenib in subsequent treatments and regorafenib was also effective in heavily treated mCRC patients. There was no difference in PFS and OS in terms of tumour sidedness by regorafenib treatment. KEY WORDS: Colorectal cancer, Regorafenib, Tumour sidedness.

Primary renal angiosarcoma: A case report and a short review of literature.

Primary renal angiosarcomas (AS) are uncommon tumors with poor prognosis. Aetiology is unknown but some unproven risk factors have been described. It is difficult to discriminate these masses from renal cell carcinomas or other renal masses with imaging modalities. Immunohistochemistry plays an important role in the diagnosis. Main treatment protocol for primary renal AS is still controversial and nephrectomy with chemotherapy and/or radiotherapy seems the only treatment option. We state a primary renal angiosarcoma case for its rareness and contribution to literature.

An Evaluation of the Information Sources of Cancer Patients' Relatives. A Prospective Survey.

Patients followed up with a cancer diagnosis must be well-informed about cancer to be able to cope with it. Besides, informing the relatives of the cancer patients who are also experiencing the same process about the diagnosis and follow-up period of cancer is highly important. In the current study, it was aimed to evaluate the information sources about cancer which are referred to by relatives of cancer patients. Three hundred ninety-one cancer patient relatives were included in medical oncology clinic between May 1 and June 30, 2015. A questionnaire was applied to the participants, comprising 12 questions to elicit demographic information and 11 questions about the information sources to which they referred. The study included 183 female and 208 male participants with a mean age of 47.9 ± 13.6 years. While the oncologists were the primary information sources referred to by 87%, the Internet was the second most preferred information source by 72%. The websites most frequently referred were the official websites (70%), the websites of oncology associations (53%), and social networks and forums (32%). The primary factors affecting the Internet preference were age, education level, income level, and place of residence. The Internet was the second most referred information source about cancer by family caregivers following oncologists. Therefore, it is of crucial importance that physicians inform patients and their relatives comprehensively as well as guiding them to correct and reliable information sources.

Whortleberry protects kidney against the cisplatin-induced nephrotoxicity: an experimental study.

PURPOSE: This study investigated the antioxidant effects of whortleberry against cisplatin-induced nephrotoxicity in rats. MATERIAL AND METHODS: This study included 48 female Sprague-Dawley rats weighing 263.68 ± 8.29 g. The rats were divided into the following six groups, with eight rats in each group: control, ethanol control, whortleberry control, cisplatin control, 16 mg/kg cisplatin +100 mg/kg whortleberry, and 16 mg/kg cisplatin +200 mg/kg whortleberry groups. Biochemical analysis was performed by measuring total oxidant status and total antioxidant status, histopathological analysis was performed by calculating proximal and distal tubule areas (µm2), and immunohistochemical analysis was performed by determining anti-Caspase-3 immunostaining. Differences among the groups were examined using one-way analysis of variance, and p < .05 was considered statistically significant. RESULTS: Cisplatin treatment decreased the total antioxidant status and increased the total oxidant status and Caspase-3 level. Moreover, it resulted in the dilatation, vacuolization and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues (p < .05). Treatment with 100 and 200 mg whortleberries increased the total antioxidant status; decreased the total oxidant status and Caspase-3 level and ameliorated distal and proximal tubule degeneration, glomerular degeneration and edema in the kidney tissues (p < .05). CONCLUSIONS: Our results indicate that the antioxidant effects of the whortleberry decrease cisplatin-associated nephrotoxicity.

Response to Cabazitaxel Beyond 20 Cycles in A Patient with Penile Metastasis of Prostate Cancer: A Case Report.

Penile metastases are extremely rare events and generally occurs at a late stage of primary disease. They mostlyoriginate from prostate and bladder in the genitourinary tract. Penile metastases have a dismal prognosis and verylow survival rates. We report a case of penile metastasis in 70-year-old geriatric male patient with prostatic adenocarcinomawho was treated with cabazitaxel chemotherapy beyond 20 cycles with a good response and acceptableminimal toxicity.

Treatment After First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance in Non-Small-Cell Lung Cancer.

Systemic treatment is the basic treatment approach to advanced-stage non-small-cell lung cancer (NSCLC), and chemotherapy and targeted treatments are commonly employed in these patients. Recently, positive results achieved with immunotherapy have led to a growing number of treatment options and prolonged survival time. Today, specific tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and the TKI crizotinib, which targets anaplastic lymphoma kinase gene rearrangement, have become the standard treatment among targeted therapies for patients with sensitive molecular anomalies. However, resistance develops against all these agents after a while. Numerous genetic mutations, T790M+ in particular, have been identified as resistance mechanisms against EGFR-TKIs, and researchers are developing specific inhibitors against them. Among those inhibitors, third-generation EGFR-TKIs such as osimertinib and rociletinib have gained prominence due to their high level of effectiveness and low toxicity profile. Besides, systemic chemotherapy and immunotherapy are proper alternatives. A second biopsy during the progression stage and better clarification of the mechanisms causing secondary resistance will enable more successful treatments in the future.

Immune Checkpoint Inhibitors in Advanced-Stage Non-small Cell Lung Cancer.

More than half of non-small cell lung cancer (NSCLC) patients are at an advanced stage at the time of diagnosis, and they have a poor prognosis. Systemic treatment is the basic treatment approach for advanced-stage NSCLC, and chemotherapy and targeted treatments are commonly used based on the molecular characteristics. Although targeted therapies have led to a significant level of improvement in terms of survival, the results are still unsatisfactory. However, considerable attention has been focused to the immunotherapy with recent positive results reported by studies on this field. In this context, a certain portion of clinical studies have shown dramatic results, and these have involved inhibitors developed particularly against the immune checkpoint protein programmed death receptor-1 and its ligand (programmed death ligand-1). This review aims to present the significance of immune checkpoint inhibitors in NSCLC and to summarize the findings of relevant contemporary clinical studies.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Patients with Neuroendocrine Tumors: An Izmir Oncology Group Study.

BACKGROUND: Several studies evaluating the prognostic factors of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) have been published. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been accepted as prognostic factors for cancer patients. MATERIALS AND METHODS: This study included 132 patients diagnosed with GEP-NETs. Peripheral blood samples were collected before the pretreatment period. RESULTS: NLR and PLR were increased as the grade increased in NETs. The embryonic origin analysis revealed higher NLR and PLR rates in NETs of foregut origin. NLR and PLR were also higher in pancreatic NET patients compared to the gastroenteric NET patients. Analysis of NETs by TNM indicated that an advanced stage was accompanied by significantly higher NLR and PLR. We found a strong negative correlation between progression-free survival and NLR and PLR. CONCLUSION: The study verified that NLR and PLR are simple laboratory findings that can be used to identify NETs with a worse outcome.

Bilateral ovarian metastasis of a Klatskin tumor: A rare case.

Metastatic carcinomas of the ovary have an important place in all ovarian cancers and tumors. They can originate from many organs and systems and may metastasize to the ovary. The most common primary origin of metastasis is the gastrointestinal tract and then breast tissue. Cholangiocellular carcinomas involving the junction of the right and left bile ducts are called Klatskin tumors, and their metastases to the ovaries are very rare. A woman aged 54 years who had been treated previously for Klatskin tumor was admitted to our clinic due to bilateral ovarian masses and high serum calcium 19-9 levels. The preoperative approach, operative, and postoperative management of Klatskin tumor is presented.