Prognostic significance of 18F-FDG PET/CT indices in metastatic renal cell cancer and evaluation of revised IMDC risk model by including 18F-FDG PET-CT parameters.

BACKGROUND: Prognostic markers in metastatic renal cell cancer (mRCC) are still insufficient. Any prognostic model objectively determines disease burden. PURPOSE: To investigate the relationship between 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and outcomes in mRCC, and to define a revised International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model for the intermediate-risk group. MATERIAL AND METHODS: A retrospective study of mRCC was conducted. To investigate the prognostic significance of 18F-FDG PET/CT parameters, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were determined in pre-treatment images. Cutoff values were defined by ROC curve analyses and their association with outcomes was analyzed. Additionally, a TLG-adjusted IMDC model was created by stratifying intermediate-risk group patients according to TLG levels. RESULTS: The study included 52 patients. The disease control rate (DCR) was 61.5% and median overall survival (OS) was 18 months (95% confidence interval=9.2-25.8). In the univariate analyses, IMDC score, MTV, and TLG were prognostic factors for Disease Control Rate (DCR), and Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS), IMDC score, lactate dehydrogenase (LDH), treatment option, MTV, and TLG were prognostic factors for OS (P < 0.05 each). In the multivariate analyses, MTV was an independent prognostic factor for DCR, and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. According to the revised-IMDC model, the intermediate-favorable group showed longer OS than the intermediate-unfavorable group. CONCLUSION: Pretreatment MTV was independent prognostic factor for DCR and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. Revised-IMDC model could identify patients with a worse prognosis among the IMDC intermediate-risk group.

A rare case of gastric cancer with bilateral breast metastasis during pregnancy.

BACKGROUND: Gastric cancer is rare during pregnancy and often diagnosed at a later stage due to overlapping symptoms of pregnancy. Breast metastasis of gastric cancer is another uncommon entity. We present a rare case of breast metastasis of gastric cancer during pregnancy. CASE REPORT: A 26-year-old female was diagnosed with gastric cancer at 14 weeks of gestation and underwent total gastrectomy. She rejected adjuvant chemotherapy and continued pregnancy without any follow-up. Cancer recurred in bilateral breasts at 34th week of gestation mimicking primary inflammatory breast cancer. MANAGEMENT AND OUTCOME: It was difficult to diagnose breast metastasis during pregnancy because of overlapping pregnancy symptoms. Following an unresponsive period to antibiotherapy, a fine needle biopsy on breast was performed and signet cell adenocarcinoma metastasis was determined. We started chemotherapy after delivery. There was a near complete response after first line of chemotherapy. Unfortunately, cancer was relapsed within three months and we started second-line chemotherapy. DISCUSSION: To our knowledge, this is the fourth case reported in medical literature of gastric cancer presented with breast metastasis during pregnancy. We will try to draw attention to diagnosis, treatment and different presentation of gastric cancer during pregnancy with review of the literature.

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

PURPOSE: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. METHODS: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. RESULTS: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). CONCLUSION: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

A rare case of primary rectal choriocarcinoma and review of the literature.

INTRODUCTION: Primary choriocarcinoma of the colon is an extremely rare neoplasm which has a poor prognosis. Only 18 cases have been previously reported in English medical literature. Here we present a case of primary rectal choriocarcinoma with a good response to chemotherapy and review the literature on this uncommon tumor. CASE REPORT: A 36-year-old woman presented with abdominal pain and vaginal bleeding. Abdominal magnetic resonance imaging revealed 6.9 × 5.3 × 6.4 cm hypervascular mass posterior to uterus very close to rectum. Beta-human chorionic gonadotropin (ß-hCG) level was markedly elevated. Low anterior resection of the rectum with lymph node dissection and total abdominal hysterectomy with bilateral salpingo-oophorectomy were performed. Pathologic diagnosis was reported as colonic choriocarcinoma with a focal component of adenocarcinoma. Post-operative magnetic resonance imaging detected multiple metastatic lesions throughout the liver. The patient was treated with systemic chemotherapy using bleomycin, etoposide and cisplatin (BEP protocol). After three cycles, ß-hCG level decreased to normal and magnetic resonance imaging showed regression of liver metastasis. However, the patient died of respiratory failure due to bleomycin toxicity and pneumonia accompanied by rapid disease progression. DISCUSSION: This is an extremely rare case of primary rectal choriocarcinoma. Due to poor prognosis of the disease, it seems very important to start prompt treatment to improve patient's survival.

Impact of the Charlson Comorbidity Index on dose-limiting toxicity and survival in locally advanced and metastatic renal cell carcinoma patients treated with first-line sunitinib or pazopanib.

BACKGROUND: Anti-angiogenic tyrosine kinase inhibitors, sunitinib and pazopanib, have proven efficacy in advanced renal cell carcinoma, with specific adverse events occurring during treatment process. Comorbidities can reflect functional status and have prognostic value in oncology patients. We aimed to assess the association of the Charlson Comorbidity Index with severe toxicities and mortality in renal cell carcinoma cases treated with front-line sunitinib or pazopanib. METHODS: Files of locally advanced and metastatic renal cell carcinoma patients who received first-line sunitinib or pazopanib were retrospectively examined. Charlson Comorbidity Index of each patient was calculated. Patients were also stratified into Memorial Sloan-Kettering Cancer Center risk groups. Predictors of dose-limiting toxicity were evaluated with binomial logistic regression analysis. Univariate and multivariate Cox regression models were utilized to determine prognostic factors for survival. RESULTS: The study included 102 patients, 64 were treated with first-line sunitinib and 38 with pazopanib. In 42 patients (41.9%), Charlson Comorbidity Index was 9 or more. Dose-limiting toxicities were significantly more frequent in Charlson Comorbidity Index ≥9 group (69% vs. 40%, p = 0.004), and Charlson Comorbidity Index independently predicted dose-limiting toxicity (Hazard ratio (HR) = 4.30, p = 0.002). After adjusting for other variables, a Charlson Comorbidity Index of ≥9 is also a significant prognostic factor for progression-free (HR = 1.76, p = 0.02) and overall survival (HR = 1.75, p = 0.03). CONCLUSIONS: Charlson Comorbidity Index may be a valuable method to estimate prognosis and optimize therapy in patients with advanced renal cell carcinoma receiving first-line sunitinib or pazopanib.

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01]. CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

The CONUT score is prognostic in esophageal cancer treated with chemoradiotherapy.

Background: Malnutrition is a frequent issue in esophageal cancer (EC). The Controlling Nutritional Status (CONUT) Score has been established as a prognostic indicator in EC patients who underwent surgery. We aimed to investigate the role of the CONUT Score in EC patients treated with chemoradiotherapy (CRT). Methods: The trial included 101 non-metastatic EC patients. Receiver operating characteristic (ROC) curve analyses were used to determine cut-off values for the CONUT Score and other indices. Cox regression analyses were performed to determine prognostic markers. Results: Of 101 patients, 59.4% (n = 60) and 40.6% (n = 41) of patients were treated with CRT alone and CRT plus surgery, respectively. ROC curve analyses determined an optimal cut-off for CONUT Score in overall survival (OS), which was 3.5 (AUC = 0.63, CI 95%: 0.51-0.76, P = 0.05). The sensitivity and specificity of CONUT were 66% and 61%, respectively. Low CONUT (≤3.5) patients had significantly longer median OS than high CONUT (>3.5) patients (57.1 vs. 23 months; P = 0.009). Multivariate regression analysis revealed a CONUT Score hazard ratio (HR) of 1.96 for OS (CI 95%: 1.03-3.75, P = 0.04). Conclusion: The CONUT Score might be a useful prognostic tool in EC patients treated with CRT. Appropriate nutritional support might provide a better prognosis, which underlines the importance of multidisciplinary assessment of malnutrition in EC patients.

The Naples prognostic score in esophagus cancer: Prognostic and beyond.

OBJECTIVES: The role of inflammation in tumor biology has been better understood over time. The utility of the Naples prognostic score (NPS), which is a novel inflammation-based marker, was shown in esophageal carcinoma (EC) patients treated with surgery. We herein presented the prognostic and predictive value of NPS in EC patients treated with upfront chemoradiotherapy (CRT). METHODS: Adult EC patients with squamous cell carcinoma or adenocarcinoma were included. Median survival was compared by log-rank test. Cox regression analyses were performed to establish the independent prognostic effect of NPS. RESULTS: Of 153 patients, 97 (63.4%) and 56 (36.6%) patients were treated with CRT alone and CRT followed by surgery, respectively. The median overall survival (OS) was significantly different among the Naples prognostic groups (NPG) (60+ months [CI 95%: NA], 27 months [CI 95%: 16.8-37.5], and 18.5 months [CI 95%: 15.3-30.7] for NPG 0,1, and 2, respectively; P=0.007). Surgery following CRT provided survival benefit in NPG 1 (65+ months with surgery vs. 17.3 months without surgery, P<0.001) and in NPG 2 (33 months with surgery vs. 15 months without surgery, P=0.009). Multivariate Cox regression analysis showed that the NPS is an independent prognostic marker for OS (HR is 1.28 for OS [CI 95%: 1.03-1.59], P=0.02). CONCLUSION: NPS might be useful as a prognostic marker in also EC patients treated with upfront CRT. Patients with high NPS may have a high risk of recurrence. Surgery might be planned in EC at the diagnosis in NPG 1 and 2.

Dynamic changes in systemic immune-inflammation index predict pathological tumor response and overall survival in patients with gastric or gastroesophageal junction cancer receiving neoadjuvant chemotherapy.

AIM: Systemic inflammation has been associated with chemoresistance and prognosis in solid tumors. Systemic immune-inflammation index (SII) is a novel marker derived from complete blood count. We investigated whether differences between SIIs measured before and after neoadjuvant chemotherapy (NACT) are associated with tumor regression grade (TRG) and survival in gastric and gastroesophageal junction (GEJ) cancer patients. METHODS: Records of gastric and GEJ cancer patients treated with NACT in two centers were evaluated retrospectively. Patients were categorized according to difference between pre- and post-NACT SII values (ΔSII). Association between clinicopathological factors and TRG was analyzed using logistic regression method. Predictors of disease-free and overall survival (DFS and OS) were determined with Cox regression models. RESULTS: The study included 140 patients. Patients with ΔSII<0 were more likely to achieve TRG 0/1 (45.2% vs. 19.1%, p = 0.003) and ΔSII<0 was an independent predictor of TRG 0/1 (OR = 6.05, p<0.001). DFS and OS of patients with ΔSII<0 were also significantly longer (p = 0.031 and p = 0.006, respectively). After adjustment for other variables, ΔSII≥0 was an independent prognostic factor for OS (Hazard ratio (HR) = 2.13, p = 0.008). CONCLUSIONS: Changes in SII, which is a low-cost and easily accessible marker, may be used to estimate prognosis, individualize postoperative treatment and optimize surveillance in gastric and GEJ cancer patients treated with NACT.

Prognostic value of Gustave Roussy immune score in operable pancreatic adenocarcinoma.

Background: The Gustave Roussy immune score (GRIm score) is a laboratory index developed to predict survival in nonsmall cell lung cancer patients undergoing immunotherapy and has shown that the pretreatment value is an independent prognostic factor for survival. In this study, we aimed to determine prognostic significance of GRIm score for pancreatic adenocarcinoma that have not been determined in the literature for pancreatic cancer before. The reason for choosing this scoring is to show that the immune scoring system works as a prognostic marker in pancreatic cancer known as immune-desert tumor via immune properties of microenvironment. Methods: Medical records of patients with histologically confirmed pancreatic ductal adenocarcinoma, who were treated and followed up between December 2007 and July 2019 at our clinic, were reviewed retrospectively. GRIm scores of each patient were calculated at the time of diagnosis. Survival analysis were performed according to risk groups. Results: A total of 138 patients were included in the study. While 111 (80.4%) patients were in the low-risk group; 27 (19.6%) were in high-risk group according to GRIm score. Median OS was 36.9 months (95% Confidence interval (CI): 25.42-48.56) in lower GRIm scores, and it was 11.1 months (95% CI: 6.83-15.44) in higher GRIm scores (P = 0.002). One-two-three-year OS rates were 85% versus 47%, 64% versus 39%, 53% versus 27% for low versus high GRIm scores, respectively. The multivariate analysis revealed that high GRIm score was an independent poor prognostic factor. Conclusion: GRIm can be used as a noninvasive, easily applicable, practical prognostic factor in pancreatic cancer patients.

Evaluation of Predictive and Prognostic Importance of Lung Immune Prognostic Index in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The systemic inflammatory response (SIR) is known as an important factor associated with tumorigenesis and tumor progression, and can be reflected by inflammatory markers. One of the markers that reflect this is the lung immune prognostic index (LIPI). It is based on a derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level. We aimed to investigate the significance of LIPI in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (NACRT). METHODS: In this retrospective study, we stratified the patients according to LIPI score as good LIPI and intermediate (int)/poor LIPI. According to pathological response to NACRT, we divided the patients into two groups as those with complete response (CR) or near-CR, and those with partial response (PR) or poor/no response. We classified CR and near-CR as good response. We evaluated the predictive and prognostic significance of LIPI for NACRT response, disease-free survival (DFS), and overall survival (OS) by univariate and multivariate analyses. RESULTS: We included 137 patients in the results, with 72 (52.6%) having good LIPI and 65 (47.4%) having int/poor LIPI. The median follow-up period was 44.7 months (range: 10-105 months). Thirteen patients (18.0%) in the good LIPI group and 22 patients (34.0%) in the int/poor LIPI group achieved good response. In multivariate analysis, we found only the LIPI score as an independent risk factor (hazard ratio (HR): 2.4, p = 0.04) for NACRT response. Median DFS was 89.2 months (95% CI: 11.4-167.0) in the int/poor LIPI group; however, the DFS of all study populations and patients in the good LIPI group did not reach the median value. In multivariate analysis for DFS, we identified abdominoperineal resection (APR) (HR: 2.21, p = 0.02), presence of tumor deposit (HR: 2.96, p = 0.003), and int/poor LIPI score (HR: 2.07, p = 0.02) as separate risk variables. OS of all study populations and the patients in the LIPI groups did not reach the median value. In multivariate analysis for OS, we identified APR (HR: 2.74, p = 0.02), surgical margin positivity (HR: 12.94, p < 0.001), and adjuvant CT (HR: 0.20, p = 0.002) as separate risk variables for OS. CONCLUSION: This is the first study investigating the predictive and prognostic significance of LIPI in LARC patients treated with NACRT. The results revealed that int/poor LIPI was associated with a higher rate of good response but shorter DFS compared to good LIPI. The baseline LIPI score serves as an easily accessible and useful prognostic index, and it has significant potential for making appropriate treatment decisions in LARC.

Age-adjusted Charlson Comorbidity Index is a valuable prognostic tool in operable soft tissue sarcoma of trunk and extremities.

BACKGROUND: Advanced age and presence of comorbidities affect prognosis and treatment decisions in patients with soft tissue sarcoma (STS). However, coeffect of age and comorbidities is still unknown. We aimed to investigate prognostic value of age-adjusted Charlson Comorbidity Index (ACCI) in trunk and extremity STS operated with curative intent. HYPOTHESIS: Preoperative ACCI might predict survival outcomes independently in patients with STS of trunk and extremities. PATIENTS AND METHODS: The study included 151 patients and ACCI was calculated for each patient. We categorized the patients into two groups according to median ACCI. We retrospectively collected data about clinicopathologic and treatment-related factors, and evaluated potential prognostic factors for disease-free survival (DFS) and overall survival (OS) using univariate and multivariate analyses. RESULTS: Median age was 50 (18-86) years. There were 89 male and 62 female patients. Lower extremities were the most common tumor sites (73.5%). Most of the patients had high grade tumors (84.1%) and stage 3 disease (66.9%). Radiotherapy and chemotherapy were carried out in 106 and 58 patients, respectively. Overall prevalence of comorbidity was 29.1%. Median ACCI was 3 (2-9). Older age (p<0.001), worse performance status (p<0.001), larger tumor size (p=0.03), higher grade tumors (p=0.03) and advanced stage (p=0.04) were associated with higher ACCI (≥3). Median follow-up time was 32 months, 50.3% of patients had disease recurrence, and 35.8% died. Median DFS (p=0.001) and OS (p=0.001) of patients with low ACCI (<3) were significantly longer than patients with high ACCI. Multivariate analysis determined ACCI as an independent prognostic indicator for both DFS (HR 1.72, p=0.02) and OS (HR 2.02, p=0.04). DISCUSSION: ACCI is a valuable prognostic tool to be used in the preoperative setting of patients with STS. Higher ACCI was found to be independently associated with worse survival outcomes. For each patient with STS, evaluating comorbidities and combining them with age appears to be a critical step in modifying therapy options. LEVEL OF EVIDENCE: IV, retrospective observational study.

Prognostic significance of mucinous histology in left­sided metastatic colorectal cancers with wild­type RAS and evaluation of backbone chemotherapy regimens.

Mucinous colorectal adenocarcinoma (MCAC) is a distinct subtype of colorectal carcinoma (CRC). The prognostic and predictive significance of mucinous histology remains controversial. It was aimed to investigate the prognostic and/or predictive role of mucinous histology in left-sided metastatic CRC (mCRC) with wild-type RAS. This is a retrospective multicenter study of mCRC treated with first line anti-EGFR combined 5-fluorouracil based chemotherapy (CT). Patients were stratified according to presence (>50% extracellular mucin) or absence of mucinous histology. Survival analyses were performed firstly regardless of treatment options and then performed as separating according to CT regimens. Additional analyses were performed for MCAC patients considering backbone CT regimens. A total of 125 patients were included, consisting of 40 (32.0%) patients with MCAC and 85 (68.0%) patients with non-MCAC. Median follow-up time was 19.7 months. Median progression-free survival (PFS) was 10.7 months in all patients, and PFS was lower in MCAC than non-MCAC (9.9 vs. 12.0 months, respectively, P=0.005). Median overall survival (OS) was 25.7 months in all patients. OS was lower in MCAC than non-MCAC (22.8 vs. 29.7 months, respectively, P=0.005). When considering backbone CT regimens, in multivariate analyses, mucinous histology was an independent prognostic factor for OS in both for mFOLFOX6 (HR: 1.92, P=0.04) and FOLFIRI (HR: 2.04, P=0.04) groups and was associated with poor PFS in only mFOLFOX6 (HR: 3.86, P<0.001) group. When outcomes were analyzed for the MCAC group, median OS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 22.47 and 14.22 months, respectively (P=0.41). Median PFS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 10.15 and 8.11 months, respectively (P=0.73). The study revealed poor prognosis of mucinous histology, both in whole study population and in backbone CT groups. Moreover, lower PFS of MCAC patients was revealed in only mFOLFOX6 group and this finding may be a valuable issue for the future research. However, considering all analyses, the present results did not indicate a special benefit of any backbone CT regimen for MCAC patients.

Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy.

AIM: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. METHODS: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. RESULTS: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB -0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB3 group compared to the pathological responder group (p = 0.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (p < 0.05). CONCLUSIONS: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis. Aims: To investigate the prognostic value of tissue-resident memory T cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas. Study Design: Retrospective cross-sectional study. Methods: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory cells and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account. Results: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range: 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn's-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn's-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29). Conclusion: Tissue-resident memory T cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.

Role of baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting survival outcomes of metastatic castration-resistant prostate cancer patients receiving first-line treatment.

OBJECTIVE: We aimed to evaluate whether baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters could be used as predictive biomarkers for survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line treatment. MATERIALS AND METHODS: This retrospective study included 54 mCRPC patients, who underwent baseline 68Ga-PSMA PET/CT imaging within 1 month before starting first-line treatment. Pre-treatment prostate-specific antigen (PSA) levels and treatments were recorded. SUVmax, SUVmean, whole-body PSMA-derived tumor volume (wbPSMA-TV), and whole-body total lesion PSMA (wbTL-PSMA) were calculated for all patients. PSA response was defined as a decline of ≥ 50% from pre-treatment value at 12 weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC. RESULTS: Docetaxel and abiraterone/enzalutamide were administered to 32 and 22 patients in the first-line setting, respectively. wbPSMA-TV (rho = 0.582, p = 0.004) and wbTL-PSMA (rho = 0.564, p = 0.007) showed moderate positive correlations with PSA levels. Older age (p = 0.02), higher wbPSMA-TV (p = 0.007), higher PSA (p = 0.01), higher number of bone metastases (p = 0.02), and lack of PSA response (p = 0.03) were significantly associated with an increased risk of mortality. Multivariate analysis determined wbPSMA-TV (HR: 1.003, 95% CI 1.001-1.004, p = 0.001) and PSA response (HR: 2.241, 95% CI 1.189-4.222, p = 0.01) as independent predictors of OS. CONCLUSION: The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC.

Rechallenge with dabrafenib plus trametinib in anaplastic thyroid cancer: A case report and review of literature.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is a highly aggressive, undifferentiated rare tumor. Median overall survival is usually between 8 and10 months, with a 1-year survival rate of 20%. Conventional anthracycline based chemotherapy regimens demonstrate low response rates with short duration. Novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape of ATC have been investigated. CASE PRESENTATION: We herein report the rechallenge of a 52-year-old ATC patient with BRAF V600E mutation with dabrafenib plus trametinib. She presented with recurrent and progressive disease despite surgery, radiation therapy, 3 different chemotherapy regimens, and combination of dabrafenib-trametinib in different settings. She was rechallenged with dabrafenib-trametinib, and had a good response. CONCLUSION: To our knowledge, this is the first ATC case who responded to dabrafenib-trametinib rechallenge, reported in the literature. We want to emphasize that combination of dabrafenib and trametinib might be a good choice for resistant locoregional and metastatic ATC patients with BRAF V600E mutation, particularly in whom rapid clinical response is urgently needed. Moreover, rechallenge with this combination should be kept in mind in selected cases.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Differences in PET/CT standardized uptake values involvement and survival compared to histologic subtypes of lung adenocarcinoma.

PURPOSE: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. METHODS: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. RESULTS: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. CONCLUSION: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.