Effect of Microsatellite Status and Pan-Immune-Inflammation Score on Pathological Response in Patients with Clinical Stage III Stomach Cancer Treated with Perioperative Chemotherapy.

Background and Objective: This study evaluated the relationship between microsatellite status (MSI) and pan-immune-inflammation score (PIV) in tumor response to neoadjuvant chemotherapy (NAC) in patients with clinical stage III gastric cancer (cStage III GC). Materials and Methods: Microsatellite instability (MSI) status was evaluated based on pathology preparations. Pan-immune-inflammation score (PIV) was obtained from pre-treatment blood tests. The relationship of both parameters with pathological complete response (pCR) was evaluated. Results: A total of 104 patients were included in this study. All the patients were stage III GC patients receiving perioperative treatment. There were 13 patients in total who achieved a pCR response. While CNS was detected in 11 of the patients who achieved a pCR, the MSI status of the other two patients was unknown. No pCR was observed in any patient with MSI-H. According to the cut-off value for PIV, 25 (24%) patients were in the PIV-low (≤53.9) group, while 79 (76%) were in the PIV-high (>53.9) group. Based on univariate analysis, a higher PIV was associated with worse outcomes for pathological response, disease recurrence, and survival (p < 0.05). Conclusions: In patients with clinically stage III GC, the presence of MSI-H may predict no benefit from perioperative treatment. Conversely, a pre-treatment PIV score using specific cut-off values may provide a positive prediction of pathological response and survival.

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.

Can peritumoral edema evaluated by Magnetic Resonance Imaging before neoadjuvant chemotherapy predict complete pathological response in breast cancer?

BACKGROUND AND AIMS: The complete pathological response (pCR) following neoadjuvant chemotherapy (NAC) in breast cancer is essential for the accurate prediction of prognosis. We aimed to evaluate the efficacy of the presence and type of peritumoral edema detected by magnetic resonance imaging (MRI) in predicting pCR to NAC in breast cancer patients. METHODS AND RESULTS: One hundred five patients with the diagnosis of invasive carcinoma were evaluated by MRI before NAC. Edema was evaluated in fat-suppressed T2-weighted images. The patients were categorized into three groups: patients with no peritumoral edema, patients with peritumoral edema, and patients demonstrating subcutaneous edema. The cases were categorized as being pCR and non-pCR. Molecular subtypes, lymphovascular invasion (LVI), tumor size, and apparent diffusion coefficient (ADC) were evaluated. A positive relationship was found between the presence of edema and tumor size. Subcutaneous edema was found to be statistically higher in non-pCR patients. While the number of pCR patients with subcutaneous edema was 17 (30.4%), the number of non-pCR patients with subcutaneous edema was 26 (53.1%) (p = 0.018). LVI was found to be statistically higher in patients with edema. The number of edema-negative and LVI (+) patients was 4 (15.4%), while the number of edema-positive and LVI (+) patients was 28 (35.4%) (p = 0.042). Intratumoral and peritumoral ADC values were significantly higher in tumors with edema. CONCLUSION: The presence of subcutaneous edema and LVI may be utilized for the prediction of pCR outcomes in breast cancer patients scheduled for NAC treatment.

Brigatinib-associated autoimmune hepatitis: A case report.

INTRODUCTION: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a wide variety of ALK mutations and ROS1 rearrangements. While pancreatic enzyme elevations due to brigatinib are well known, we wanted to present a case that caused liver toxicity. CASE REPORT: ALK and ROS1 translocations were detected in a 58-year-old patient diagnosed with metastatic lung adenocarcinoma. In the patient who had a good response with brigatinib, more than 5-fold elevation was detected in liver enzymes at the fifth month of treatment. MANAGEMENT & OUTCOME: After excluding other hepatitis factors, the patient was thought to have autoimmune hepatitis, and methylprednisolone was started and liver enzymes were decreased. DISCUSSION: Increased creatine kinase and lipase levels are common side effects associated with brigatinib, while liver toxicity is rare. Autoimmune hepatitis due to brigatinib was considered because of hepatic toxicity that developed in the fifth month of treatment and responded well to steroids.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study.

INTRODUCTION: Approximately 20-33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs' solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. RESULTS: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). CONCLUSIONS: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Ruxolitinib Reduces Oxidative Stress in Patients With Primary Myelofibrosis: A Multicenter Study.

Introduction Primary myelofibrosis (PM) has a lower overall survival rate than other myeloproliferative neoplasms, and leukemic transformation is the most common cause of death. Increased oxidative stress has an important role in leukemic transformation in these patients. In this study, we aimed to find an answer to the question, "Could Ruxolitinib, which has been widely used in patients with myelofibrosis in recent years, have a role in reducing oxidative stress in these patients?". Methods A total of 106 patients with PM and 111 healthy volunteers were included in this study. We collected the serum samples of healthy volunteers and patients with myelofibrosis at the time of diagnosis and one month after the initiation of Ruxolitinib treatment. Ischemia modified albumin (IMA), native thiol, total thiol, and disulfide levels were studied. The disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were calculated. Results IMA, native thiol, total thiol, disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios at the time of diagnosis were significantly different in patients with myelofibrosis compared to the control group (p=0.001). Ruxolitinib significantly reduced oxidative stress when the measurements in the first month after Ruxolitinib were compared with those at the time of diagnosis (p=0.001). In patients with ASXL1 mutation, intermediate-2 risk, and high-risk according to the Dipps-plus score, the decrease in oxidative stress in the first month of treatment was more significant than at the time of diagnosis. Conclusion Ruxolitinib may be an effective treatment for reducing oxidative stress in patients with PM. The reduction in oxidative stress parameters with treatment in patients with ASXL1 mutation, intermediate-2, and high-risk patients was observed to be higher.

Prognostic Importance of Inflammatory Indexes in Patients Treated by Pazopanib for Soft Tissue Sarcoma.

BACKGROUND: The goal of this study was to evaluate the predictive and prognostic importance of the lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (DNLR), and systemic immune inflammation index (SSI) in STS cases treated with pazopanib. METHODS: Thirty STS patients treated with pazopanib were included in this study. SSI, DNLR, LMR, and NLR values were calculated at baseline and in the first month. Median values of these predictors in these patients (SSI (944), DNLR (1.8), LMR (2.7), and NLR (3.0)) were taken as cutoff values. The associations between the survival time (both overall survival (OS) and progression-free survival (PFS)) and cutoff values were evaluated using Kaplan Meier curves and Cox regression models. RESULTS: Patients with low SSI, NLR, and DNLR values at pretreatment and after the initial response had longer OS (for OS - p = 0.024, p = 0.015, and p = 0.041, respectively). Longer OS was also found in patients who showed increasing LMR and decreasing NLR after one month of therapy (for ΔLMR, p = 0.016; for ΔNLR, p = 0.016). Pa-tients with low SSI and NLR values at pretreatment and after the initial response had longer PFS (for PFS, p = 0.014, p = 0.04, p ˂ 0.001, respectively). In terms of initial responses to treatment, SSI, NLR, DNLR, and increased LMR were detected as independent risk factors in univariate analysis, but initial response was found to be the only independent risk factor for PFS in multivariate analysis. CONCLUSIONS: Low values of SSI, NLR, and DNLR at pretreatment and at initial response may predict long-term survival rates. After one month of treatment with pazopanib, decreased NLR and increased LMR are predictive of favorable outcomes in these cases.

Panitumumab Associated Acute Pancreatitis.

INTRODUCTION: The addition of panitumumab to chemotherapy in wild-type metastatic colon cancer contributes to survival. While the skin related side effects of panitumumab are well known, we wanted to present a case where it was a possible cause of acute pancreatitis. CASE REPORT: The FOLFOX regimen was started in a 67-year-old patient with sigmoid colon cancer and multiple liver metastases. After 2 cycles, genetic tests were concluded and panitumumab 6 mg/kg was added to the treatment. The patient who presented with abdominal pain 2 days after the treatment was hospitalized with acute pancreaatitis. MANAGEMENT & OUTCOME: Abdominal tomography of the patient was compatible with acute pancreatitis. Oral intake was stopped, IV hydration was started. The patient, whose complaints regressed, was discharged on the 3rd day of hospitalization. DISCUSSION: Skin side effects related to panitumumab are observed quite frequently. Although panitumumab related gastrointestinal side effects have been reported, there is no data on acute pancreatitis. Panitumumab was added to the chemotherapy regimen he received, and it was thought that panitumumab might be the etiological factor in the case who developed pancreatitis.

Integration of low muscle mass into the IPS system and its prognostic significance in patients with Hodgkin's lymphoma.

Aim: The aim of this study is to determine whether a novel prognostic score can be obtained by including low muscle mass in the international prognostic score (IPS) system. Materials & Methods: Psoas muscle areas were determined in the PET/CT scans of the patients taken for staging at the time of diagnosis and after two cycles of ABVD. After evaluating the effect of low muscle mass on overall survival, receiver operating characteristic (ROC) analyzes were performed by including it in IPS systems. Results: Overall survival was significantly lower in patients with low muscle mass. Adding low muscle mass to IPS scores increased AUC, sensitivity and specificity. Conclusion: The integration of low muscle mass into the IPS scoring systems increased the success of these systems in predicting a prognosis.

Lay abstract Hodgkin's lymphoma is a cancer that responds well to standard treatments. However, the cancer recurs 30% of the time. Improved scoring systems could help better predict the outcomes of treatment. The 'International Prognostic Score' (IPS) system is an algorithm currently used to predict the possibility of death and treatment complications. In this study, low muscle mass is evaluated as data that could be added to the current scoring system to improve the system's ability to predict outcomes. Data from the scans of patients before and after treatment were used to determine the muscle mass. It was found that survival was significantly lower in patients with low muscle mass. This suggests that this information is highly effective in predicting the outcomes of Hodgkin's lymphoma patients.

Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.

Background and objective Male breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients. Materials and methods We retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded. Results The mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4. Conclusion The hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.

The Correlation of the Neutrophil-Lymphocyte Ratio and the Platelet-Lymphocyte Ratio With Pathological Findings in Neuroendocrine Tumors.

Introduction The relationship between clinical prognostic factors and blood neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in some tumors has been investigated. In this study, we examined whether there is a relationship between pathological prognostic factors and NLR as well as PLR only in neuroendocrine tumors (NETs). Methods A total of 115 patients with a NET diagnosis between 2014-2020 were included in the study. The efficiency of NLR and PLR in predicting distant metastases was determined by analyzing the receiver operating characteristic (ROC) curve. The relationship between histopathological parameters was also compared. Results The cut-off value of NLR was 3.01 for predicting distant metastasis. At this value, the specificity was 73.7%, the sensitivity was 70.7%, and the likelihood ratio was 2.51. There was a significant relationship between NLR and tumor localization, histological grade, mitosis, Ki-67, distant metastasis, and lymphovascular invasion (all p<0.001). The cut-off value of the PLR in predicting distant metastasis was 134.4. At this value, the specificity was 59.6%, the sensitivity was 58.6%, and the likelihood ratio was 1.44. There was no significant relationship between PLR and the histopathological findings (all p>0.05). Conclusions In our study, a high histological grade, high mitosis, a high Ki-67 proliferation index, distant metastasis, and lymphovascular invasion were found in patients with NLR at a cut-off value above 3.01. However, we could not attain the same results for PLR. For trucut and endoscopic biopsies in particular, follow-up of patients with grades 1 and 2 NETs along with histopathological findings and evaluation of NLR in peripheral blood may be useful. NLR, which is an easily accessible inflammatory marker, can be used as an independent predictive factor in NETs.

Cardiac Chamber Quantification by Echocardiography in Adults With Sickle Cell Disease: Need Attention to Eccentric Hypertrophy.

Introduction and aim Sickle cell anemia (SCA) is the most common hemoglobinopathy worldwide, and cardiovascular diseases are the most common causes of death. In these patients, cardiac remodeling begins from childhood and leads to sickle cell cardiomyopathy in the following years. Concentric hypertrophy and eccentric hypertrophy are known to predict early cardiac events. This study aims to reveal the relationship between cardiac remodeling types and survival in patients with SCA and investigate the factors that may affect left ventricular mass. Materials and methods A total of 146 patients with SCA were included in the study, and the left ventricular mass index (LVMI) and relative wall thickness (RWT) of the patients were calculated according to echocardiographic measurements, and the patients were categorized into normal, concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) groups. Results The median age of the patients is 32 (18-72). In logistic regression analysis, hemoglobin S (HbS) and ferritin levels were independent predictors for LVMI (p = 0.01 and p < 0.001, respectively). It was observed that 56 (38.4%) of the patients had normal left ventricles, 24 (16.4%) had CR, 21 (14.4%) had CH, and 45 (30.8%) had EH. 31 (21.2%) of the patients died. When we look at the survival curves, there was a statistically significant difference between the four groups (log-rank p < 0.001). It was observed that patients with EH were the group with the lowest probability of survival. Conclusion Cardiac death is one of the most common causes of death in patients with SCA. Early detection of cardiac disorders and starting treatment may be important in reducing mortality in these patients.

Neutrophil-to-lymphocyte ratio is prognostic in recurrent glioblastoma multiforme treated with bevacizumab plus irinotecan.

Aim: We intended to survey the prognostic utility of pretreatment neutrophil-to-lymphocyte ratio (NLR) as a novel prognostic index in recurrent glioblastoma multiforme (R-GBMs) treated with bevacizumab plus irinotecan (BEVIRI). Patients & methods: The present retrospective investigation incorporated the R-GBMs patients who underwent BEVIRI. The pre-BEVIRI NLR was calculated for each patient by utilizing the complete blood count tests obtained on the first day of BEVIRI. Results: The data of a total of 103 patients were analyzed. The ideal cutoff was identified at 3.04 (area under the curve: 60%; sensitivity: 60.3%; specificity 60%) for the pre-BEVIRI NLR. Low-NLR group had significantly longer overall survival times than the high-NLR group (15.8 vs 9.3 months; p = 0.015). Conclusion: NLR might be utilized as a novel biomarker in the prognostic stratification of the R-GBMs treated with BEVIRI.

Can the mesorectal fat tissue volume be used as a predictive factor in foreseeing the response to neoadjuvant chemoradiotherapy in rectum cancer? A CT-based preliminary study.

PURPOSE: This study was to investigate the effect of mesorectal fat tissue volume (MRV) on the pathological response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. METHODS: 88 patients who had been diagnosed with locally advanced rectal cancer between January 2017 and June 2020 were reviewed retrospectively. The total abdominal, subcutaneous, visceral, and mesorectal fatty tissue components were measured semiquantitatively by two radiologists using computed tomography (CT)-based findings. The patients were divided into two groups as those with and without a pathological response to nCRT. The relationship of MRV with the other fat tissue components of the body was also evaluated. RESULTS: We performed a retrospective analysis of 88 patients (mean age 62.7 years [range, 33-90 years]; 31 males and 57 females). A positive response to nCRT was present in 47 patients. There were 59 patients with stage 3 disease. 46 patients demonstrated lymph node involvement. The mean MRV was 69.6 ± 31.0 ml in no-response group and 105.8 ± 47.5 ml in response-positive patients (p < 0.05). MRV showed the highest correlation with visceral fat volume (VFV). There was a negative correlation between the MRV and the N stage. A cut-off value of ≥ 69.4 for MRV predicted the repsonse to nCRT, with 82.9% sensitivity and 58.5% specificity [AUC: 0.757 (0.653-0.842), p < 0.001] in receiver operating characteristic (ROC) curve analysis CONCLUSIONS: MRV can be used as a novel parameter in predicting of pathological response to nCRT in locally advanced rectal cancer patients.