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Introduction: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). Methods: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. Results: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56–69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7–71.8), the median OS was 19.3 months (95% CI: 14.1–24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23–3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01–5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47–22.61 for poor risk) were found to be independent prognostic factors. Conclusion: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.

130 Background: Tyrosine kinase inhibitors (TKI) are the most common oral drugs in cancer patients. Similarly, proton pump inhibitors (PPI) are commonly used to relieve dyspeptic symptoms in patients with cancer. However, gastric pH levels may affect the absorption of TKI through the gastrointestinal system. However, all TKIs do not have the same chemical structure, and the absorption rate of each TKI depends on their solubility in different gastric pH levels. Limited data is available about the clinical outcomes of concomitant use of PPI and regorafenib in patients with metastatic colorectal cancer (mCRC). We present here the results of the multicenter study following the initial results of our single-center experience. Methods: Patients with mCRC treated with regorafenib were included in this multicenter and retrospective study. Patients prescribed PPI after initiation of regorafenib were assigned to the PPI user group, and the remaining patients were assigned to the PPI non-user group. To exclude immortal time bias, the log-rank test was performed between PPI non-user and all patients. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and adverse events (AEs) profile. Results: Two hundred and seventy-two patients from eight cancer centers were included in this study. Most patients were male (59.9%), had liver metastasis (62.1%), and received regorafenib in the third line (52.2%). The median age at the initiation of regorafenib was 60 years (interquartile range (IQR): 51-66)). Eastern Cooperative Oncology Group performance score was 0 or 1 in approximately three out of four patients. The rate of patients with K-RAS mutation was 46.7%. There were 131 (48.2%) and 141 (51.8%) in the PPI user and non-user groups, respectively. The most prescribed PPI was pantoprazole (40.4%). At a median 34.2 months follow-up, the median OS was 6.9 months (95% Confidence Interval (CI): 5.3-8.5) and 7.7 months (95% CI:6.6-8.8) in the PPI non-user and all patients, respectively. No statistical significance was observed between the groups (p = 0.913). The median TTF was 3.3 months (95% CI: 2.6-3.9) and 3.4 months (95% CI:2.9-4.0) in the PPI non-user and all patients, respectively. No statistical significance was observed between the groups (p = 0.651). In the time-dependent covariate Cox regression model, there was no difference between PPI user and non-user groups in OS and TTF (adjusted Hazard Ratio (aHR):0.96, 95% CI:0.74-1.24, p = 0.735 for OS; aHR:0.88, 0.68-1.14, p = 0.354 for TTF). The rates of all AEs were also similar in the PPI user and non-user groups (p = 0.628). Conclusions: To our knowledge, this was the first study evaluating the effect of concomitant use of PPI and regorafenib in patients with mCRC, and no adverse survival and safety outcome was observed with the concomitant use of PPI and regorafenib in those patients.

This study aims to assess the effect of primary tumour resection (PTR) on patients with metastatic colorectal cancer (mCRC) treated with cetuximab.This retrospective cohort study was conducted in a tertiary cancer center in Turkey. Patients with mCRC between January 2009 and December 2020 were extracted from the electronic hospital management system. Patients with RAS wild-type synchronous metastatic left-sided colon or rectum cancer who had cetuximab-containing treatment protocol were included in the study. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcome was response rates.A total of 111 patients with mCRC were included in this study. PTR was performed in 57.7% of all patients. Fifty-nine (53.2%) and 52 (46.8%) patients had rectal and left colon tumours, respectively. The combination treatment with cetuximab was FOLFIRI in 62.2% and FOLFOX in 29.7% of all patients. In subgroup analysis, the median PFS was 7.9 and 9 months in PTR (+) and PTR (-) patients, respectively. The difference between the groups was not statistically significant (P = 0.3). The median OS was 33 months in all patients. In subgroup analysis, the median OS was 39 and 27.9 months in PTR (+) and PTR (-) patients, respectively. The difference between the groups was statistically significant (P = 0.002). After adjusting for confounding factors, PTR and ECOG performance score were the independent prognostic factors for OS.PTR improved the OS in patients with RAS wild-type synchronous left-sided colon or rectum cancer treated with cetuximab-containing chemotherapy regimens.

To assess the prognostic effect of pan-immune inflammation value (PIV) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) or enzalutamide.Patients with mCRPC treated with AA or enzalutamide between January 2010 and June 2021 were included in this study. The most recently examined complete blood count values in the 1-month period before treatment were used for calculating PIV. The relationship between overall survival (OS) and PIV was evaluated by multivariate analysis. By using PIV and lactate dehydrogenase (LDH) levels which had shown survival effect at multivariate analysis, PIV-LDH combined score was established.A total of 114 patients were included in this study. At the median follow-up of 34.6 months (95% confidence interval [CI]: 32.4-36.8), the median OS was 21 months (95% CI: 17.6-21.3). The median OS in the low-PIV group was significantly higher than in the high-PIV group (34.4 months (95% CI: 21.3-47.5) vs. 14.3 months (95% CI: 10.0-18.7), p 0.001). In the multivariate analysis for OS, high PIV (hazard ratio [HR]: 1.86, 95% CI: 1.11-3.13, p = 0.018) and LDH value 1.5 times the upper limit of normal and above (HR: 3.65 95%, CI: 1.86-7.16, p 0.001) were associated with shorter OS. When survival analysis was performed according to the PIV-LDH combined score, the median OS was 34.4 months (95% CI: 22.2-46.6) in the low-risk group, 17.7 months (95% CI: 11.7-23.6) in the intermediate-risk group, and 8.4 months (95% CI: 5.1-11.7) in the high-risk group (p 0.001). The C-index of the combined PIV-LDH score was higher than the C-index of PIV (0.65 vs. 0.61).In this study, we demonstrated that PIV was an independent prognostic factor for OS in patients with mCRPC treated with AA or enzalutamide. Additionally, PIV-LDH combined score may be considered a promising composite peripheral blood-based biomarker to predict OS in those patients.

Visceral metastasis (VM) and a higher number of bone metastasis generally define high volume/risk in patients with metastatic castration-sensitive prostate cancer (mCSPC). Subgroup analysis of pivotal trials did not show a clear benefit of second-generation non-steroidal anti-androgens (NSAAs) in patients with VM. However, subgroup analysis of the trial assessing abiraterone acetate, a CYP 17 inhibitor, plus prednisone (AAP) showed an improved overall survival (OS) in patients with mCSPC with VM. We searched MEDLINE, Web of Science, and congress abstracts for the phase III randomized controlled trials of second-generation NSAAs and AAP in patients with mCSPC. In this pooled analysis, we included 6485 patients from the 6 phase III trials. The rate of patients with VM was 15.2%. Interestingly, in contrast to NSAAs, AAP seems to be effective in improving OS among patients with VM (hazard ratio, HR: 0.89, 95% CI, 0.72-1.11, P = .30 for second-generation NSAAs; HR: 0.58, 95% CI, 0.40-0.84, P = .004 for AAP). In contrast, both second-generation NSAAs (HR: 0.63, 95% CI, 0.57-0.70, P < .001) and AAP (HR: 0.68, 95% CI, 0.57-0.81, P < .001) improved OS in patients without VM. In this pooled analysis, we demonstrate that while AAP provided an OS improvement in patients with VM, second-generation NSAAs did not demonstrate a similar OS benefit in this population.

Purpose:The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment.Patients and Methods:Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test for BRCA1, BRCA2 (BRCA), and ATM alterations in ctDNA. Only patients from Cohort A (BRCA/ATM alteration positive by tissue testing) were evaluated. We compared clinical outcomes, including radiographic progression-free survival (rPFS) between the ctDNA subgroup and Cohort A.Results:Of the 181 (73.9%) Cohort A patients who gave consent for plasma sample ctDNA testing, 139 (76.8%) yielded a result and BRCA/ATM alterations were identified in 111 (79.9%). Of these, 73 patients received olaparib and 38 received control. Patients’ baseline demographics and characteristics, and the prevalence of HRR alterations were comparable with the Cohort A intention-to-treat (ITT) population. rPFS was longer in the olaparib group versus control [median 7.4 vs. 3.5 months; hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.21–0.53; nominal P < 0.0001], which is consistent with Cohort A ITT population (HR, 0.34; 95% CI, 0.25–0.47).Conclusions:When tumor tissue testing is not feasible or has failed, ctDNA testing may be a suitable alternative to identify patients with mCRPC carrying BRCA/ATM alterations who may benefit from olaparib treatment.

HIV-infected patients are more susceptible to cancer due to their immune-compromised condition and HIV infection. Chronic inflammation and immune dysregulation are the main causes of cancer development in these patients. Because of lymphopenia and an immune-compromised condition, most HIV-infected patients with cancer were not considered for cytotoxic therapies, such as chemotherapy and radiotherapy. Immune checkpoint inhibitors (ICIs) have become a game-changer in many cancer types. However, not enough prospective data is available regarding the use of ICIs in HIV-infected patients with cancer. Retrospective data from case reports/series showed that ICIs are safe in HIV-infected patients with cancer.

ABS TRACT Objective: Pancreatic cancer is one of the leading causes of cancer-related death. Despite the introduction of new therapeutic agents, survival rates remain low. Furthermore, few trials have evaluated the options for second-line therapy and the prognostic variables. In this study, we aimed to determine the real-world efficacy and prognostic parameters of second-line treatment for advanced pancreatic cancer. Material and Methods: Patients with advanced pancreatic cancer from different centers who received second-line treatment were enrolled in the study. The patients’ demographic, clinical, and pathological characteristics were retrieved retrospectively. Results: A total of 161 patients were enrolled in the study. The majority of the patients (50.3%) received oxaliplatin plus fluoropyrimidine as second-line treatment. The median progression-free survival and overall survival for the entire cohort were 2.5 months and 4.5 months, respectively. In univariate anal-yses, an Eastern Cooperative Oncology Group performance status ≥2, age ≥65 years, hypoalbuminemia, thrombocytosis, presence of metastatic peritoneal disease, elevated alkaline phosphatase and carcinoembryonic antigen levels, and a neutrophil-lymphocyte ratio (NLR) ≥3 were identified as poor prognostic factors. In multivariable analyses, low albumin level (p=0.031) and high NLR (p=0.05) were found to be independent prognostic factors for overall survival. Conclusion: Pancreatic cancer is a unique malignancy, and advanced disease has a dismal prog-nosis. In univariate analyses, we identified multiple factors that were poor prognostic variables. In particular, the albumin level and NLR were independent prognostic factors for overall survival, and these parameters might be useful in selecting the second-line treatment and pre-dicting the survival of these patients.

This 5-year analysis of real-world data confirms the durable response and long-term survival with ICTs in a broader range of patients with metastatic urothelial carcinoma. After 24 months, PFS and OS curves remained nearly flat. The safety profile was consistent with previous reports, and no new safety signals were observed. Background: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). Patients and Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. Conclusion: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients.

Contains fulltext : 291600.pdf (Publisher’s version ) (Open Access) BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

Purpose: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment. Patients and Methods: Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test for BRCA1, BRCA2 (BRCA), and ATM alterations in ctDNA. Only patients from Cohort A (BRCA/ATM alteration positive by tissue testing) were evaluated. We compared clinical outcomes, including radiographic progression-free survival (rPFS) between the ctDNA subgroup and Cohort A. Results: Of the 181 (73.9%) Cohort A patients who gave consent for plasma sample ctDNA testing, 139 (76.8%) yielded a result and BRCA/ATM alterations were identified in 111 (79.9%). Of these, 73 patients received olaparib and 38 received control. Patients’ baseline demographics and characteristics, and the prevalence of HRR alterations were comparable with the Cohort A intention-to-treat (ITT) population. rPFS was longer in the olaparib group versus control [median 7.4 vs. 3.5 months; hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.21–0.53; nominal P < 0.0001], which is consistent with Cohort A ITT population (HR, 0.34; 95% CI, 0.25–0.47). Conclusions: When tumor tissue testing is not feasible or has failed, ctDNA testing may be a suitable alternative to identify patients with mCRPC carrying BRCA/ATM alterations who may benefit from olaparib treatment.

Immune checkpoint inhibitors (ICIs) have started a new era in treating patients with cancer. The effect of comorbidities and concomitant drug use on ICIs have become of interest in those patients. Data about the impact of hyperglycemia on response to ICIs in cancer patients are limited. All advanced-stage cancer patients treated with ICIs in Ankara University Medical Oncology Department were retrospectively evaluated. Patients treated in expanded access programs or clinical trials were excluded from the study. A total of 137 patients were included in this study. The most common primary tumor type was malign melanoma (32.8%) and nivolumab (62.3%) was the most common used ICI. More than half of patients (57.7%) had lung metastasis at the initiation of ICIs. Thirty-five patients (25.5%) had diabetes before initiating ICIs. Median baseline fasting glucose level was higher in patients with diabetes than those without diabetes (117 mg/dl vs. 99 mg/dl, P = 0.002). In all patients, median overall survival and progression-free survival were 11.3 [95% confidence interval (CI), 8.1-14.4) and 5.9 (95% CI, 3.6-8.3) months, respectively. In multivariate analysis, diabetes was found to increase risk of death [hazard ratio (HR), 2.09; 95% CI, 1.27-3.43, P = 0.004) and disease progression (HR, 2.01, 95% CI, 1.29-3.09, P = 0.002). Hyperglycemia might decrease response to ICIs in patients with advanced cancer. This research area is still an unmet need in the immunotherapy era. Prospective studies are needed to elucidate the effect of hyperglycemia on the response to ICIs.

Background Histamine and H1 receptor play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) may increase the effect of ICIs. This study aimed to evaluate impact of antihistamines on oncological outcomes of ICIs. Patients and Methods This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. Results A total of 133 patients receiving ICIs in the metastatic setting were included. Melanoma (33.1%) was the most common tumor type. The most common ICI was nivolumab (63.2%). Fifty-five (38.4%) patients received antihistamines concomitantly with ICIs. The most common antihistamine was pheniramine (85.5%). The median progression-free survival (PFS) (8.2 vs. 5.1 months, log-rank p = 0.016) and overall survival (OS) (16.2 vs. 7.7 months, log-rank p = 0.002) were longer in patients receiving antihistamines concomitantly with ICIs. In multivariate analysis, PFS (Hazard Ratio (HR) = 0.63, 95% CI:0.40–0.98, p = 0.042) and OS (HR = 0.49, 95% CI:0.29–0.81, p = 0.006) were also better in those patients after adjusting for confounding factors, such as performance status, bone or liver metastasis, and concurrent chemotherapy. Conclusion This study suggested that antihistamines may enhance the efficacy of ICIs in patients with advanced cancer. If validated in prospective trials, antihistamines and ICIs combinations might be new options to improve oncological outcomes.

Background: A novel prognostic model was recommended for patients with metastatic RCC (mRCC) by the International mRCC Database Consortium (IMDC). In this study, we aimed to externally validate a novel risk model for the IMDC-favorable risk group in patients with mRCC. Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) is a multicenter registry that includes 13 cancer centers in Turkey. As described by Schmidt et al., 3 parameters (ie, time from diagnosis to systemic therapy 80, and the presence of brain, liver, or bone metastasis) were used to divide the IMDC favorable risk group into 2 new categories: very favorable and favorable risk groups. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) and objective response rate (ORR) in the very favorable and favorable risk groups were the secondary endpoints. Results: A total of 545 patients with mRCC from all IMDC risk groups and 112 patients from the favorable risk group were included in this study. According to the novel classification model, 44 (39.3%) and 68 (60.7%) patients with former favorable risk were categorized into very favorable and favorable risk groups, respectively. The median OS (55.8 months vs. 34.2 months, P = .025) and TTF (25.5 months vs. 15.5 months, P = .010) were longer in the very favorable risk group than in the favorable risk group. The concordance index of the new IMDC model in all patients was 0.65 for OS. Despite the higher ORR in the very favorable risk group than in the favorable risk group, the difference between the groups was not statistically significant (52.4% vs. 44.7, P = .573). Conclusions: This was the first study to externally validate the novel IMDC risk model presented in the American Society of Clinical Oncology Genitourinary Cancers Symposium 2021. 35970759

Aim To assess the actionable genomic landscape of colon adenocarcinoma in the primary and metastatic tumor tissues. Methods The data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) were used in this study. Colon adenocarcinoma patients with primary and metastatic tissue samples (distant organ and lymph node) were selected. Patients with samples from a local recurrence, not otherwise specified tumor samples, and data not collected for sampling localization were excluded. Results A total of 3286 and 1727 patients were included in the primary and metastatic tissue sample groups, respectively. There was no difference between the groups in Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation rates. The rates of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and mismatch repair (MMR) gene mutations were higher in the primary tumor tissues than in the metastatic tumor tissues. There was also no difference between the groups in other actionable gene alterations (e.g. ERBB2 amplification and neurotrophic receptor tyrosine kinase (NTRK) 1 and NTRK3 fusions). In contrast to all cohorts, in Asian and black patients, there was no difference in actionable genomic landscape between the primary and metastatic tumor tissues. Conclusion This study had the largest number of colon cancer patients that evaluated the actionable genomic alterations in primary and metastatic tumor tissues. BRAF and MMR gene alterations were more frequent in the primary tumor tissues than the metastatic tumor tissues.

Background Pan-immune-inflammation value (PIV) is an easily accessible immune marker based on peripheral blood to estimate prognosis in patients with cancer. This study evaluates the prognostic value of PIV in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. Methods In this retrospective cohort study, patients with mRCC treated with nivolumab in the second line and beyond were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. PIV was calculated by using the following formula: neutrophil (103/mm3) x monocyte (103/mm3) x platelet (103/mm3) / lymphocyte (103/mm3). Results A total of 152 patients with mRCC were included in this study. According to cut-off value for PIV, 77 (50.7%) and 75 (49.3%) patients fell into PIV-low (\(\le\)372) and PIV-high (>372) groups, respectively. In multivariate analysis, PIV-high (HR:1.64, 95% CI: 1.04–2.58, p = 0.033 for overall survival (OS); HR:1.55, 95% CI: 1.02–2.38, p = 0.042 for progression-free survival (PFS)) was independent risk factor for OS and PFS after adjusting for confounding variables such as performance score, the International mRCC Database Consortium (IMDC) risk score, and liver metastasis. Conclusion This study established that pre-treatment PIV might be a prognostic biomarker in patients with mRCC treated with nivolumab in the second line and beyond.

Aim: To evaluate polypharmacy (PP) in patients with metastatic colorectal cancer receiving regorafenib. Methods: Patients with metastatic colorectal cancer receiving regorafenib were included and divided into two categories by their PP status: PP- (+ (≥5 regular drug use/day). Results: 80 patients were included. 31 (38.7%) patients had PP. The median number of drugs used was three and seven in PP- and PP+ patients, respectively. Antiemetics (26.5%) and antacids (48.4%) were the most common drugs used by PP- and PP+ patients, respectively. In multivariate analysis, the risk of death was higher in PP+ patients (hazard ratio: 2.1; 95% CI: 1.2–3.7; p = 0.005). Conclusion: PP was an independent prognostic factor for overall survival in patients with metastatic colorectal cancer receiving regorafenib.

To evaluate the accuracy of Ga-68 prostate-specific membrane antigen positron-emission-tomography and computed-tomography(PSMA-PET/CT) in primary nodal staging of prostate cancer (PCa), and the predictive value of volumetric parameters derived from Ga-68- PSMA-PET/CT data in lymph node(LN) metastasis and correlation with histopathological and surgical outcomes.Seventy-seven patients with newly diagnosed, biopsy-proven PCa who underwent Ga-68-PSMA-PET/CT for primary staging of disease and underwent radical prostatectomy with extendend pelvic LN dissection were evaluated retrospectively. 2 experienced nuclear medicine specialists have retrospectively reviewed PET/CT images blinded to all histopathological and clinical data. Sensitivity, specificity, positive predictive value(PPV), and negative predictive value(NPV) for the detection of LN metastases were analyzed per-patient. Volumetric and semiquantitative PET parameters of the primary prostate lesions including SUVmax,metabolic tumor volume(MTV), and total lesion uptake(TLU) were measured and recorded.Primary tumor SUVmax, MTV and TLU were found significantly higher in patients who were in higher ISUP Grade groups 3,4,5 after surgical treatment (P = 0.021,P = 0.049,P = 0.032, respectively). The sensitivity, specificity, PPV and NPV on LN metastasis detection of Ga-68-PSMA-PET/CT was found 60%, 91%, 82% and 78% respectively. Although the distribution of the measured primary tumor MTV and TLU values were higher in histopathologically proven LN metastasis positive patients compared to negative patients, only TLU was statistically significant(P = 0.023). Increase in primary tumor TLU values were correlated with higher pT stages and surgical margin positivity(P = 0.034).Ga-68-PSMA-PET/CT is of clinically valuable for primary staging. Measuring and adding these 2 parameters in routine clinical evaluation may increase the prediction power of high-grade disease confirmed by surgery.

474 Background: Anti-tumor activity and manageable safety profile of immune checkpoint blockade therapies (ICT) have been demonstrated in previous clinical trials in patients with metastatic urothelial carcinoma. To the best of our knowledge, very limited real-life data is available with the long follow-up time that confirms the durable antitumor activity and safety of ICT. In this study, we reported the real-life results of 56 months follow-up data of urothelial carcinoma patients who were treated with ICT. Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT included in the study. The primary endpoint was the overall response rate (ORR); secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of the ICT treatment, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 185 eligible patients were analyzed, 11.9% of these patients received the ICT as the first line, 76.8 % as the second line, and 11.3 % as the third or more line of treatment. The median age of the patients was 66 years, and 156 (84.3%) were male (37-86). The majority of patients (93.5%) had ECOG PS scores of 0–1 and primary tumor in the bladder was predominant (86.7%). The median follow-up time was 47(1.15-56) months. The complete response rate to ICT, partial response rate, and ORR were 10.3% (n = 19), 19.5% (n = 36), and 29.8% (n = 55), respectively. The median duration of response was 33.1 months (95% CI, 16.5–49.7). Of the fifty-five patients who responded to treatment, 28 (51%) had an ongoing response at the time of the analysis. Median PFS and OS was 3.8 (2.6–5.1) months and 8.9 (6.8–11.1) months, respectively. 56-month PFS and OS rate was 9.2% and 11.4%, respectively. 56-month PFS and OS rate for CR and PR was 56.2% and 20%, respectively. Fifty-nine percent of patients experienced a treatment-related adverse event of any grade, and 32 (17.3%) of patients had a grade 3–4 treatment-related adverse event. Because of treatment-related side effects, treatment was discontinued in 8 (4.3%) patients and adverse event that required systemic steroid use was reported in only 13 (7%) patients. Four patients (2.2%) died due to treatment-related causes. Conclusions: This 56-month analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients. The safety profile was consistent with prior reports, and no new safety signals emerged.

481 Background: In this study, we evaluated RECIST criteria-based objective response rate (ORR) as potential surrogate endpoints for overall survival (OS) in patients who were treated with immune checkpoint inhibitors therapy (ICT) and with long-term follow-up in metastatic urothelial carcinoma. Methods: The primary endpoint was overall ORR and OS, duration of treatment (DOR) with ICT. ORR was analyzed using Fisher’s exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method. Results: The median follow-up time was 58 (1.15–71) months (mo). Progression developed in 94 (47%) patients during the first three months of treatment with ICT. The rate of complete response (CR) to ICT, partial response (PR) rate, and stable disease were 10% (n=20), 23% (n=46), and 20% (n=41), respectively. There was an imbalance in baseline characteristics between patients who had ORR and non-responder groups (Table). The 5–year OS rates for CR and PR were 73% and 23%, respectively. The median DOR for CR, PR, and SD were 51.8 mo% (44.5–59.1), 20.7mo (16.7–24.6), and 8.8 mo (5.5–12.1), respectively. Of the sixteen (80%) patients who had CR and 14 (30%) patients who had PR had an ongoing response at the time of the analysis. In univariate analysis, neutrophil-to-lymphocyte ratio (NLR) >3, liver metastases, ECOG PS ≥1, and hemoglobin levels below 10 mg/dl, PR, and CR were all significantly associated with OS. In multivariate analysis, liver metastases [HR=2.3; 95% CI 1.3-4.2; p < (0.004)] were independent related variable with short OS. Other hand, PR [HR=0.3; 95% CI 0.15-0.5; p < (0.001)] and CR [HR=0.06; 95% CI 0.014-0.27; p < (0.001)] were associated with improved OS. Conclusions: This five-year analysis of real-world data indicated a significant correlation between ORR, especially CR and OS in patients who received immune checkpoint inhibitors in metastatic urothelial cancer. Therefore, the identification of a potential surrogate marker for survival in patients treated with ICT would represent an important advance in the early identification of patients’ response or resistance to ICT.

Aim: To investigate the prognostic value of the systemic immune-inflammation index (SII) and its impact on survival in patients with metastatic renal cell carcinoma (mRCC).Methods: A total of 706 patients with mRCC treated with tyrosine kinase inhibitors (TKIs) (i.e., sunitinib, pazopanib) were retrospectively analyzed. All patients were classified into either a high-SII group or a low-SII group based on the cut-off value of SII at 756, which was the median SII level of our study group. Results: The median age of patients was 60 (interquartile range (IQR):53-67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. The rates of patients in favorable, intermediate, and poor “International mRCC Database Consortium (IMDC)” risk groups were 20.1%, 57.6%, and 22.2%, respectively. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. At the median of 48.6 months follow-up, the median overall survival (OS) was 34.6 months and 14.5 months in the low- and high-SII groups, respectively (pConclusion: Pre-treatment level of high SII might be considered as a predictor of poor prognosis in patients with mRCC treated with TKIs.

Aim To evaluate the prognostic role of the systemic immune-inflammation index (SII) in patients with operable gastric cancer. Methods We assessed 354 patients with operable gastric cancer from tertiary centers in Turkey. SII was calculated by following formula: [neutrophil (cellsx109/L) x platelet (cellsx109/L)] / lymphocyte (cellsx109/L). The best cut-off value for SII was determined by using “receiver operating characteristics (ROC)” analysis. We used log-rank and Cox-regression analysis for survival analyses. Results One hundred twenty patients were in the late recurrence group (recurrences have developed 36 months after the surgery). SII was not a prognostic factor in the early recurrence group. However, relapse-free survival (RFS) was longer in SII-low patients than SII-high patients in the late recurrence group. In multivariable analysis, SII was the only independent prognostic factor for RFS in the late recurrence group (Hazard Ratio (HR): 5.42, 95% CI:1.18-24.82, p=0.03). Conclusion SII was an independent prognostic factor for RFS in GC patients with late recurrence. Late recurrence risk was higher in SII-high patients than SII-low patients. Inflammation contributes to tumor progression, invasion, and metastasis. Prolonged exposure to chronic inflammation could explain the results of this study.

A 60-year-old man with prostate cancer (PC) was admitted to our hospital in October 2009 for follow up visit. He underwent radical prostatectomy for PC five years ago. The patient's physical examination and complete blood count, biochemical investigations, and chest x-ray were within normal limits. The patient's carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) levels were 529 ng/mL (normal