Impact of antihistamine use on the survival outcomes of immune checkpoint inhibitors in advanced cancer patients.

Histamine and H1 receptors play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) might increase the effect of ICIs. This study aimed to evaluate the impact of antihistamines on the oncological outcomes of ICIs. This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. 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, P  = 0.016) and overall survival (OS) (16.2 vs. 7.7 months, 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. 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.

Chronic hyperglycemia based on diabetes is independently associated with decreased survival in patients with advanced cancer treated with immune checkpoint inhibitors.

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.

The prognostic role of polypharmacy in metastatic colorectal cancer patients treated with regorafenib.

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) and 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.

Regorafenib is a targeted therapy option that is used in patients with chemotherapy-refractory metastatic colorectal cancer. Because of the chemotherapy-refractory stage of the disease, patients are prone to use more medications for symptom palliation. Polypharmacy (PP) refers to the drug burden in an individual, and the use of five or more drugs in a day is usually considered to represent PP. In this study, the authors assessed the impact of PP in patients with metastatic colorectal cancer treated with regorafenib. The authors' study found that PP had a negative impact on survival outcomes in these patients. This is why inappropriate drug use should be assessed at each visit and the medication discontinued if it is not an essential part of the treatment.

The relationship between clinicopathological parameters and PD-L1 expression level in advanced stage non-small cell lung cancer.

Introduction: Clinicopathological parameters related to programmed death ligand 1 (PD-L1) expression levels have been investigated in several studies. However, the results of these studies are conflicting and vary in different populations. This study aimed to investigate the relation of clinicopathological parameters with PD-L1 expression level in advanced stage non-small cell lung cancer patients. Materials and Methods: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The data of clinicopathological parameters was collected. Clinicopathological parameters in relation to PD-L1 expression levels (0%, 1-50%, and >50%) were analyzed as univariable and multivariable. Result: In total, 384 patients were enrolled. PD-L1 expression in tumor cells was between 1-50%, and >50% in 41.4%, and 23.4% of patients, respectively. There was no PD-L1 expression in 35.2% of the patients. In univariable analysis, we found that the parameters associated with PD-L1 expression levels revealed that metastatic site number, the subtype of cancer, diagnostic material type, platelet number, and LDH level were statistically significant. Adenocarcinoma frequency was higher in tumors that had PD-L1 expression >50% than in tumors that did not express PD-L1 and the difference was statistically significant (p= 0.04, coefficient= 0.3, 95% CI 0.09-0.94). Cytology as diagnostic material was significant in PD-L1 level 1-50% comparing to >50% (p= 0.02, coefficient= 2.2, 95% CI= 1.08-4.46). Conclusions: According to the results of our study, many of the clinicopathological parameters are not related to the PD-L1 level. The histological subtype and diagnostic material may affect the level of PD-L1 expression.

ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis.

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on 31 March 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

Prevalence, etiology and risk factors of anemia in patients with newly diagnosed cancer.

PURPOSE: To determine the prevalence of anemia, and to evaluate the etiology and risk factors of anemia in patients with newly diagnosed cancer. METHODS: In this cross-sectional study, 310 patients with newly diagnosed cancer who were referred to a university hospital in Turkey over a 6-month period and 218 age-matched healthy individuals as controls were evaluated in terms of anemia: complete blood count (CBC), ferritin, transferrin saturation (TS%), serum iron (SI), cobalamin (B12), and folate levels. Carcinoma of the breast (21.3%), lung (12.9%), and gastrointestinal tract (GIT) (35.8%) accounted for the majority of the patients, and 44.7% of the patients had metastatic disease. RESULTS: Anemia was observed in 49.7% of patients with cancer and in 11.9% of healthy controls (p < 0.001). SI and TS% were lower in patients with cancer than in the controls (p < 0.001); however, the median serum ferritin level, which is also an acute-phase reactant, was higher in the patient group than the healthy matched controls (42.2 ng/mL and 41 ng/mL, respectively, p < 0.001). Folate and B12 deficiencies were seen more frequently in the cancer group than in the controls [6.5% and 0.9% (p < 0.001); 39.3% and 18.9% (p < 0.05), respectively]. In the cancer group, anemia was seen more frequently in the metastatic subgroup than in the non-metastatic subgroup (59.7% and 55.3%, respectively, p < 0.05). The prevalence of anemia was similar in both groups of patients with and without primary GIT cancers, as well as in patients who did and did not undergo tumor surgery (p > 0.05). CONCLUSION: This study showed that, at the time a patient is diagnosed as having cancer, the patient already has a significant risk for anemia, nearly five times that of healthy people. Having metastatic disease, and having nutritional deficiencies as iron, B12, and folate were evaluated as possible risk factors for anemia in patients with newly diagnosed cancer, whereas cancer with GIT localization and previous history of tumor surgery were not.

Posttraumatic growth and death anxiety in caregivers of cancer patients: PHOENIX study

Background/aim: Posttraumatic growth (PTG) is defined as positive psychological changes following a challenging or traumatic life event. The purpose of this study is to define the predictors of PTG and death anxiety (DAN) in caregivers of cancer patients and evaluate the impact of DAN on PTG. Materials and methods: The caregivers of cancer patients were evaluated using structured questionnaires, including a validated PTG scale and Templer death anxiety scale. Results: In 3 different cancer centers, 426 participants were evaluated. In multivariate analysis of factors associated with PTG, a high DAN score was the only parameter associated with high PTG scores [OR: 1.6, CI (95%) 1.02­2.5, P = 0.03]. In multivariate analysis of factors associated with DAN, female sex was the only risk factor for high DAN scores [OR: 1.6, CI (95%) 1.1­2.8, P = 0.049]. There was a positive correlation between PTG and DAN scores (r = 0.15, P = 0.001). Higher DAN scores were associated with positive impacts on self-perception (37.0 versus 35.0, P = 0.02), philosophy of life (16.0 versus 13.0, P = 0.035), and changes in relationship (16.0 versus 14.0, P = 0.01) Conclusions: This is the first report regarding the association between DAN and PTG. We found a positive impact of death anxiety on psychological changes in caregivers of cancer patients.

Comparison of Gemcitabine monotherapy with Gemcitabine and Cisplatin combination in metastatic pancreatic cancer: a retrospective analysis.

PURPOSE: Gemcitabine is among the standard first-line agents for the treatment of metastatic pancreatic cancer. However, as the median survival with gemcitabine monotherapy is 6 months, different combinations are being studied for better, prolonged survival. In this multicenter study, we aimed to compare the results of gemcitabine monotherapy with those of gemcitabine and cisplatin combination therapy as first-line treatments for metastatic pancreatic cancer. METHODS: Data of 664 patients diagnosed with metastatic pancreatic cancer between January 2007 and December 2016 from seven oncology centers in Turkey were retrospectively evaluated, and 319 patients with gemcitabine alone (n=138) or gemcitabine and cisplatin combination (n=181) as first-line treatment were included. RESULTS: The median patient age was 62 years (range 42-79), being 60 years (42-75) in the gemcitabine/cisplatin arm and 67 years (52-79) in gemcitabine alone arm. no complete response was observed in either arm, whereas partial response rates were 30.1% in gemcitabine/cisplatin arm and 15.3% in gemcitabine alone arm (p=0.001). median overall survival was 8 months (95% CI:7.7-10.2) and was significantly longer in the gemcitabine/cisplatin arm than in the gemcitabine alone arm (10 vs. 6 months, p=0.004). CONCLUSION: The cemcitabine and cisplatin combination therapy as first-line treatment of metastatic pancreatic cancer yields significantly prolonged survival over gemcitabine monotherapy. In patients with favorable performance conditions, the combination therapy should be preferred.

Severe drug interactions and potentially inappropriate medication usage in elderly cancer patients.

PURPOSE: Due to more comorbidities, polypharmacy is common in elderly patients and drug interactions are inevitable. It is also challenging to treat an elderly patient with a diagnosis of cancer. Prevalence and clinical impacts of drug interactions and using potentially inappropriate medications (PIMs) have been studied in geriatric patients. However, these are not well defined in oncology practice. The purpose of this study is to define the prevalence of PIMs and severe drug interactions (SDIs) in elderly cancer patients and investigate the factors associated with them. METHODS: Patients more than 65 years of age in both inpatient and outpatient clinics were evaluated. Patient, disease characteristics, and medications used were collected by self reports and medical records. Drug interactions were checked with Lexicomp® and PIM was defined with 2012 update of Beers criteria. Severe drug interactions are defined with category D or X DIs. Logistic regression was used to compute odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between SDIs, PIMs, and clinical parameters. RESULTS: Four hundered and forty-five elderly patients (286 outpatient, 159 inpatient), with a median age of 70 (65-89) were evaluated. SDIs were present in 156 (35.1 %) of patients, 81 (28.3 %), and 75 (47.2 %) for outpatient and inpatients, respectively (p < 0.001). PIMs were present in 117 (26.6 %) of the patients, 40 (14.2 %), and 77(48.4 %) for outpatient and inpatients, respectively (p < 0.001). In multivariate analysis; polypharmacy (≥5 drugs), inpatient status and diagnosis of lung cancer were associated with severe DIs. Polypharmacy, inpatient status, and bad performance score (ECOG 3-4) were associated with PIMs. CONCLUSIONS: Nearly one third of the elderly cancer patients are exposed to severe drug interactions and PIMs. Clinicians dealing with elderly cancer patients should be more cautious when prescribing/ planning drugs to this group of patients. More strategies should be developed in this group of patients to minimize the medications prescribed and prevent severe DIs.

Vaccination in oncology practice and predictors.

PURPOSE: Despite, vaccination is a highly effective and widely recommended for prevention of certain infections, vaccination coverage is very low. The purposes of this study were to evaluate the attitudes of medical oncologists towards vaccination and to identify predictors of intention to recommend vaccination in patients with cancer. METHODS: A structured questionnaire is formed to evaluate the daily practice of vaccination. Turkish medical oncologists were invited to this study via email, SMS, or phone call. Questionnaire was filled out and the data were stored in an online survey platform. RESULTS: Two hundred seventy-three medical oncologists participated in the survey. Influenza, Pneumococcus, and hepatitis B were the most commonly recommended vaccines (87.1, 72.8, 67.0%, respectively). Patients with lung cancer, lymphoma and breast cancer were the main malignancies that medical oncologists suggest vaccination (68.1, 68.1, 24.6%, respectively). The most common times for vaccination were during remission/follow-up period (68.4%) or before beginning chemotherapy (64.1%). Only 23.4% of the physicians thought that their recommendation for vaccination was efficient and adequate. Lack of time and lack of knowledge or experience about vaccination are the most common limitations. There is a positive correlation between experience in the field and evaluating patients for vaccination (r = 0.390, p < 0.001); on the other hand, there is negative correlation between number of patients seen per day and evaluating patients for vaccination (r = -0.080, p = 0.18). Experience with autologous or allogeneic bone marrow transplant patients is related with more tendency to evaluate patients for vaccination (p < 0.001). CONCLUSIONS: Degree of experience in oncology especially in bone marrow transplant units and total number of patients seen per day are important predictors of vaccination practice in oncology. The frequency of recommendation increases with degree of experience, knowledge, and visit time per patient.

Breast cancer survivors suffer from persistent postmastectomy pain syndrome and posttraumatic stress disorder (ORTHUS study): a study of the palliative care working committee of the Turkish Oncology Group (TOG).

PURPOSE: Persistent postmastectomy pain syndrome (PMPS) is one of the most important disturbing symptoms. Posttraumatic stress disorder (PTSD) is an anxiety disorder which is characterized by reactions to reminders of the trauma that has been experienced. The purpose of this study is to evaluate the predictors of PMPS and PTSD in Turkish breast cancer survivors and the correlation between PMPS and PTSD. METHOD: The study is designed as a multicenter survey study. Breast cancer patients in remission were evaluated. Patients were evaluated with structured questionnaires to assess the PMPS and clinical parameters associated with it. The Turkish version of the posttraumatic stress disorder checklist-civilian version (PCL-C) was used. RESULTS: Between February 2015 and October 2015, 614 breast cancer survivors in outpatient clinics were evaluated. The incidence of PMPS documented is 45.1 %. In the multivariate analysis low income, presence of PTSD and <46 months after surgery were associated with increased risk of PMPS. PTSD was documented in 75 %, and the mean PCL-C score was 32.4 ± 11.1. PMPS and being married at the time of the evaluation were linked with PTSD. CONCLUSIONS: It is the first data about the association between PMPS and PTSD. The clinicians should be aware of PMPS and PTSD in breast cancer survivors.

Peripheral blood mononuclear cell microchimerism in Turkish female patients with systemic sclerosis.

OBJECTIVES: To investigate microchimerism (Mc) in peripheral blood mononuclear cells (PBMC) taken from female patients with systemic sclerosis (SSc) and healthy females. We also intended to research the association between Mc and the clinical subsets. METHODS: This study included 50 females with lcSSc, 30 females with dcSSc and 40 healthy females. The Y-chromosome sequences were studied by RT-PCR in DNA obtained from PBMC. RESULTS: Mc was found in 28 (35 %) patients and 8 (20 %) healthy controls as well as in 6 dcSSc patients with son(s) (27.3 %), 10 lcSSc patients with son(s) (32.3 %) and 7 control females with son(s) (18.9 %) (p > 0.05). Mc was detected in 6 nulliparous lcSSc patients (31.6 %) and in 1 nulliparous dcSSc patient (11.1 %) (p > 0.05). The mean time elapsed between the first pregnancy and the diagnosis of SSc was 3.5 (0-49) years in the Mc-positive patients and 14 (0-55) years in the negative patients (p = 0.020). The mean modified Rodnan skin scores (ModRSS) of the patients with and without Mc was 10 (4-24) and 13 (4-26), respectively (p = 0.038). The relationship between Mc and the system involvement, disease severity, autoantibody profile, number of children and age of children was not found. CONCLUSIONS: Various etiological factors rather than just one play a role in the development of scleroderma. Mc is thought to be one factor that shortens the elapsed time of disease development in SSc. Mc is inversely related to the ModRSS, and no association was detected between Mc and autoantibodies or the clinical subsets.

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

Impact of low sodium values on survival outcomes of patients with cancer receiving immune checkpoint inhibitors.

Background: Low serum sodium affects cancer prognosis, but its impact on immunotherapy is unclear. Objective: Assessing the association of pre- and post-ICI treatment sodium levels with survival. Methods: We retrospectively analyzed patients receiving ICI in January 2012-December 2023, collecting serum sodium levels at treatment initiation and 4 weeks post-ICI, with overall survival (OS) as the primary outcome. Results: Low sodium was observed in 125 and 119 patients pre-and post-treatment respectively. Pre-ICI and post-ICI low sodium correlated with decreased OS [10.6 vs. 22.9 months (p = 0.001) and 11.6 vs. 27.2 months (p = 0.009)]. Multivariate analysis identified pre-ICI low sodium [HR: 1.685; 95% CI: 1.050-2.705; p = 0.031] as an independent risk factor for worse OS. Conclusion: Low baseline serum sodium was an independent risk factor for poor OS in patients treated with ICIs.

This study explored how sodium levels impact cancer patients' outcomes during treatment with immune checkpoint inhibitors (ICIs). We examined sodium levels before and after ICI treatment in patients with cancer. Low sodium levels both before and after treatment were associated with poorer outcomes. Specifically, patients with low sodium levels before treatment had shorter survival times compared to those with normal levels. Similarly, patients with low sodium levels after treatment had shorter survival times compared to those with normal levels. These findings suggest that low baseline sodium levels could indicate poorer outcomes in patients receiving ICIs.

Enhancing the Anti-angiogenic Effect of Bevacizumab with ACE Inhibition on mCRC.

INTRODUCTION: Angiotensin 2 has been shown to promote angiogenesis through multiple pathways. Reduction of angiotensin 2 production by angiotensin-converting enzyme inhibitors (ACEi) could enhance the antiangiogenic effect of bevacizumab and lead to improved survival. METHODS: Data from metastatic colorectal cancer (mCRC) patients treated with bevacizumab in our hospital were retrospectively collected. Patients were divided into groups taking ACEi or angiotensin receptor blockers (ARB) or neither. We performed survival analysis and COX proportional hazard modelling and calculated the hazard ratio (HR). Multivariate analyses were performed to measure the impact of factors affecting survival, and subgroup analyses were performed for patients younger than 65 years. RESULTS: We enrolled 133 patients who received bevacizumab therapy. Eighty patients were male, and 53 were female. Twenty-three patients received ACEi treatment, and 34 patients received ARB. The median age was 58 years. Progression-free survival was higher in the ACEi group than in the ARB group or in the group receiving neither (7.66 vs. 5.98 vs. 5.0 months; p < 0.01), corresponding to a HR of 0.44 for the ACEi group (95% CI 0.26-0.74). Overall survival was not significantly longer in the ACEi group than in the ARB group or in the group receiving neither (22.0 vs. 23.5 vs. 19.7 months; p = 0.30), HR 0.66 (95% CI 0.38-1.2). In a subgroup analysis, overall survival was higher in patients younger than 65 years in the ACEi group (45.0 vs. 16.2 months; p = 0.02). CONCLUSION: In the final analysis, ACEi use in patients treated with bevacizumab resulted in prolonged progression-free survival, but this did not affect overall survival. Because our study is the first to look at the enhancement of the effect of bevacizumab by ACEi treatment and ACEi receiving patients are older, it would be useful to confirm our results by randomized trials.

The effect of primary tumour resection on patients with synchronous metastatic colorectal cancer treated with cetuximab-containing regimens.

BACKGROUND: This study aims to assess the effect of primary tumour resection (PTR) on patients with metastatic colorectal cancer (mCRC) treated with cetuximab. METHODS: 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. RESULTS: 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. CONCLUSION: PTR improved the OS in patients with RAS wild-type synchronous left-sided colon or rectum cancer treated with cetuximab-containing chemotherapy regimens.

Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group.

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

PURPOSE: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. METHODS: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. RESULTS: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. CONCLUSION: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

Vitamin D deficiency in cancer patients and predictors for screening (D-ONC study).

INTRODUCTION: Vitamin D is a prohormone that is vital for calcium/phosphate balance, bone structure, and physiological functioning. Vitamin D deficiency (VDD) is an important clinical problem worldwide. However, there are no standardized protocols for screening of patients with a diagnosis of cancer. The purpose of this study is to define the prevalence of VDD in cancer patients and establish the predictors of VDD to address a specific group of patient for screening. MATERIAL/METHODS: The study was designed as a retrospective case-control study. The patients cared in the outpatient clinic between December 2016 and May 2018 with a diagnosis of cancer were evaluated. The clinical properties and the 25(OH) D levels were evaluated. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between VDD and clinical parameters. RESULTS: In 2 cancer centers, 706 patients with a diagnosis of cancer were evaluated. Median 25(OH) D level was 12.2 ng/mL (2.1-96.4). VDD was present in 509 (72.0%) of patients. The multivariate analysis of factors associated with VDD showed that female gender (OR: 1.5 [95% CI: 1.05-2.4], P = 0.026), low sun light exposure (OR: 1.4 [95% CI: 1.009-2.1], P = 0.045), being under palliative (OR: 1.5, [95% CI: 1.008-2.4] P = 0.04) or adjuvant setting (OR: 2.6 [95% CI: 1.3-5.1], P = 0.006), and history of gastrointestinal surgery (OR: 1.8, [95% CI: 1.03-3.2] P = 0.03) were associated with VDD. The female patients with headscarf had lower 25(OH) D levels than without group (10.5 ng/mL vs 23.4 ng/mL, P < 0.001) and they had more VDD (77.2% vs 29.4%, P < 0.001). CONCLUSION: Our study concluded that prevalence of VDD is high in cancer patients and female gender, low sun light exposure, being under palliative or adjuvant setting, and history of gastrointestinal surgery are associated with VDD. These parameters should be used for selecting patients for screening.

Prognostic Importance of Bone Marrow Uptake on Baseline 18F-FDG Positron Emission Tomography in Diffuse Large B Cell Lymphoma.

AIM: To define the role of 18F-flourodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the detection of bone marrow (BM) involvement in patients with diffuse large B cell lymphoma (DLBCL). MATERIALS AND METHODS: Fifty-four (mean age: 55.5 ± 18.3 years, 20 female and 34 male) DLBCL patients who underwent pretreatment 18F-FDG PET/CT were included to the study. Focal or diffuse BM 18F-FDG uptake that is higher than mediastinal blood pool uptake was accepted as positive. After staging of disease by CT and 18F-FDG PET/CT, all the patients received R-CHOP treatment after diagnostic blinded bone marrow biopsy (BMB). Presence of positive BM uptake in 18F-FDG PET/CT and histopathological examination results of BMBs were analyzed by Chi-square test. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 18F-FDG PET/CT in the detection of BM involvement were calculated. Prognostic importance of the presence of BM 18F-FDG uptake was analyzed by Kaplan-Meier analysis. RESULTS: BM 18F-FDG uptake was detected in 8 patients. Histopathological examination of BMB revealed BM involvement in 6 out of 8 patients. BMB was negative in all patients who have no 18F-FDG uptake in the evaluation of PET/CT images. Sensitivity, specificity, accuracy, PPV, and NPV of 18F-FDG PET/CT in the detection of BM involvement were calculated as 100%, 96%, 96%, 75%, and 100%, respectively. In the Kaplan-Meier analysis, we found that presence of pretreatment 18F-FDG uptake in BM has a prognostic importance. Whereas mean time to progression (TTP) in patients with BM uptake was 32.25 ± 10.9 months and mean TTP in those without was 51.69 ± 3.6 months (p = 0.013). CONCLUSIONS: BM uptake in pretreatment 18F-FDG PET/CT is an important prognostic factor in DLBCL patients. Moreover, in consideration of high NPV, 18F-FDG PET/CT could eliminate unnecessary BMB in FDG-negative patients.