The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma.

INTRODUCTION: Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. METHODS: We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients' body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. RESULTS: Median splenic volume change was 10% (ranging from - 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1-4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1-6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. CONCLUSION: Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

Greater financial toxicity correlates with increased psychological distress and lower quality of life among Turkish cancer patients.

PURPOSE: This study aims to investigate the factors that influence financial toxicity and its effects on both quality of life and psychological distress in Turkish cancer patients. METHODS: Data from 400 cancer patients receiving chemotherapy at a public university in Turkey was analyzed. The Comprehensive Score for Financial Toxicity (COST), Patient Health Questionnaire for Depression and Anxiety (PHQ-4), and Functional Assessment of Cancer Therapy-General (FACT-G) were used to measure financial toxicity, psychological distress, and health quality of life, respectively. RESULTS: Patients' median COST score was 22 (SD = 10.1; range: 1-44) and was consistent with mild financial toxicity. Financial toxicity was associated with lower education level (p < 0.001), lower monthly income (p < 0.001), being a woman (p = 0.021), living in another city (p = 0.012), and previous cancer surgery (p = 0.02). A negative and statistically significant correlation was found between financial toxicity and quality of life (r = - 0.139; p = 0.005) and psychological distress (r = - 0.398; p < 0.001). CONCLUSION: This investigation demonstrated that financial toxicity was a significant determinant of quality of life and psychological distress.

Nivolumab-ipilimumab combination therapy-induced seronegative encephalitis; rapid response to steroid plus intravenous immunoglobulin (IVIG) treatment.

INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICIs) against malignant melanoma and numerously solid tumors has been demonstrated in several clinical studies. The incidence of immune-related adverse effects (irAEs) has increased after the rapidly expanding indications and clinical applications of ICIs. We present a case of nivolumab and ipilimumab-induced encephalitis with rapidly worsening consciousness and full recovery following ICIs suspension and high-dose steroid coupled with intravenous immunoglobulin (IVIG). CASE REPORT: A 67-year-old woman was diagnosed with stage 4 BRAF wild malignant melanoma with metastasis to the axillary and mediastinal lymph nodes. Beyond progression with dacarbazine, ipilimumab and nivolumab combination were administered at the second-line treatment of metastatic setting. A week after the first cycle patient was reported to have a fever of more than 38°C. Subacute cognitive impairment including mild changes in behavior was reported on the third day of fever. She suddenly developed confusion, dysarthria, and motor dysfunction a few days later. Due to the altered mental status accompanied by fever, lumbar puncture was performed with a pre-diagnosis of encephalitis, meningitis, and leptomeningeal carcinomatosis. MANAGEMENT & OUTCOME: After excluding viral and autoimmune encephalitis, high-dose methylprednisolone was administered in addition to IVIG for 5 days with the diagnosis of immunotherapy-related encephalitis according to the recommendations for the management of irAEs. On the second day of the treatment patient's neurological status improved gradually. DISCUSSION: Being aware of symptoms of serious neurological irAEs associated with ICIs can prevent complications and improve survival.

LAG-3 expression in tumor microenvironment of triple-negative breast cancer.

BACKGROUND: This study aimed to evaluate the expression of lymphocyte activation gene-3 (LAG-3) and its relationship with programmed cell death ligand-1 (PD-L1) in triple-negative breast cancer (TNBC). METHODS: : LAG-3 and PD-L1 was evaluated in tumor-infiltrating lymphocytes (TILs) using immunohistochemistry (IHC). The chi-square test was used to estimate the associations between LAG-3, PD-L1 and clinicopathological characteristics. Correlation between LAG-3 stromal TIL (sTIL), LAG-3 intraepitelial TIL (iTIL) and PD-L1 was assessed with using the Spearman's correlation coefficient. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The percentages of LAG-3 sTIL+, LAG-3 iTIL+, PD-L1+ tumor cells and PD-L1+ inflammatory cells were 52%, 42%, 14% and 70%, respectively. A strong positive correlation between LAG-3 sTIL and LAG-3 iTIL (r = 0.874, p < 0.001) and a moderate positive correlation between LAG-3 sTIL and PD-L1 (r = 0.584, p < 0.001) were found. LAG-3 and PD-L1 status did not significantly affect overall survival (OS) (HR: 0.56 (95% CI: 0.15-2.11) (p = 0.397), HR: 2.70 (95% CI: 0.56-13.02) (p = 0.215), respectively). DISCUSSION: High levels of LAG-3 and PD-L1 expression were detected in patients with TNBC. Although their contribution to survival could not be determined, the high expression rates of PD-L1 and LAG-3 may help identify the subgroup of TNBC that would benefit from immunotherapy.

Clinical and laboratory outcomes of the solid cancer patients reinfected with SARS-CoV-2.

Introduction: The objective of this study was to evaluate the clinical and laboratory outcomes of solid cancer patients who were reinfected with COVID-19. Methods: Patients who were tested negative on the COVID-19 PCR test and those with improved clinical conditions after infection with COVID-19 were enrolled in this study. Patients who received a positive COVID-19 PCR test 28 days after the initial positive PCR test were considered as reinfected. Results: A total of 1024 patients with the diagnosis of solid malignancy and COVID-19 PCR positivity were examined. The reinfection rate was 3.1%. Mortality rate of reinfection was 34.3%. The serum ferritin and creatinine values in reinfection were found to be significantly higher than the first infection (respectively; p = 0.015, p = 0.014). Conclusion: This study has demonstrated one of the first preliminary clinical results of COVID-19 reinfection in solid cancer patients.

Plain language summary Solid cancer patients are at a higher risk than general population in terms of COVID-19 infectivity and COVID-19-associated death and disease. It is also known that COVID-19 infection has a more severe course in immunocompromised patients. Solid cancer patients may be a vulnerable subgroup of patients to reinfection with COVID-19. The rate of reinfection was 3.1% (n = 32) in our study population of 1024 solid cancer patients who were tested positive on a COVID-19 PCR test. The death rate of the patients with solid cancer was 34.3% (n = 11). In addition, we demonstrated that intensive care follow-up is significantly longer during the reinfection period. It was demonstrated that the time between the last dose of chemotherapy for the patients and the reinfection COVID PCR positivity did not affect the death rate. The COVID-19 pandemic has affected people's daily lives and treatments in many aspects. Owing to the high death rate of reinfection, even if cancer patients have reinfection, our approach is to continue cancer treatment as soon as the patient is cured. Finally, we support the priority vaccination of cancer patients.

Current status of biosimilars in Turkey: A survey among medical oncologists.

INTRODUCTION: To evaluate biosimilar understanding and preference trends of medical oncologists in Turkey. METHODS: A survey consisting of 24 multiple-choice questions with checkbox answers was conducted among medical oncologists. The questionnaire was divided into five parts to some intentions: demographic characteristics, general knowledge about biosimilars, knowledge about local approval and reimbursement issues, individual preference trends, and ranking the knowledge of their own. All answers were analyzed as whole cohort, specialists and fellows. RESULTS: Fellows (n = 47) consisted 42%, and academic clinicians (n = 37) consisted 35% of the participants. In the whole cohort, the overall rate of correct answers was 55.1% in the general knowledge about the biosimilars part, and 26.7% in the local approval and reimbursement issues part. At all, 57.7% of the participants declared that they object to switch from a reference product to a biosimilar product. The rate of those who defined themselves as extremely knowledgeable decreased from 8.1% to 2.7% in the whole cohort at the end of the survey. CONCLUSION: The need for more accurate and clarified local regulations and education emerging in the biotechnology era must be met.

Predictive ability of the G8 screening test to determine probable sarcopenia and abnormal comprehensive geriatric assessment in older patients with solid malignancies.

BACKGROUND: Pre-treatment evaluation for sarcopenia is recommended in cancer patients. New screening tests that are less time-consuming and can identify patients who will potentially benefit from geriatric assessment are being developed; the G8 geriatric screening test is one such example. We aimed to investigate whether the G8 screening test can detect probable sarcopenia and is valid and reliable compared to a comprehensive geriatric assessment (CGA) in Turkish older adults with solid cancers. METHODS: We included solid cancer patients referred to a single center. Probable sarcopenia and abnormal CGA were defined as low handgrip strength. Cut-offs for handgrip strength in the Turkish population have been previously determined to be 32 kg for males and 22 kg for females and impairment in at least one of the CGA tests, respectively. The CGA tests comprised KATZ Basic Activities of Daily Living Scale Lawton-Brody Instrumental Activities of Daily Living Scale, Mini-Mental-State Examination Scale, Geriatric Depression Scale-15, and Mini-Nutritional Assessment Short Form. Receiver operating characteristic curve analyses evaluated the test's predictive ability. Intra-rater and inter-rater reliabilities were assessed. RESULTS: The median age of the 76 patients included was 72 (65-91) years. There was a moderate correlation between handgrip strength and the G8 test total score. The sensitivity and specificity of the G8 test to detect probable sarcopenia alone (cut off score = 12.5) were 50 and 92%, respectively (AUC: 0.747; p < 0.001); to determine abnormal CGA plus probable sarcopenia (cut off score = 13) were 93.33 and 86.89%, respectively (AUC: 0.939; p < 0.001); and to detect abnormal CGA alone (cut off score = 14) were 79.63 and 95.45%, respectively (AUC: 0.893; p < 0.001). The G8 test results agreed with those of CGA (κ = 0.638; p < 0.001). Both inter- and intra-rater assessments of G8 scores revealed a strong agreement (Interclass correlation coefficient = 0.979, p < 0.001 and ρ = 0.994, p < 0.001, respectively). CONCLUSIONS: The Turkish version of the G8 test is a good screening tool to detect probable sarcopenia alone and in conjunction with abnormal CGA in older patients with solid malignancies. The G8 screening tool may thus be useful in detecting probable sarcopenia in Turkish older adults with solid cancers.

Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model.

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme.

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.