A simulated trial with reinforcement learning for the efficacy of Irinotecan and Ifosfamide versus Topotecan in relapsed, extensive stage small cell lung cancer.

OBJECTIVES: Synthetic data may proxy clinical data. At the absence of direct clinical data, this study aimed to compare Irinotecan and Ifosfamide (II) with Topotecan in synthetic, recurrent small cell lung cancer (SCLC) patients within a simulated clinical trial. MATERIALS AND METHODS: Two simulation stages were conducted. Initially, 200 recurrent SCLC cases were simulated to replicate a previous phase 3 trial, testing the utility of Cox proportional hazards model and simulation methodology together, where patients were randomized to receive Cyclophosphamide, Adriamycin, Vincristine (CAV) or Topotecan. In the second stage, 600 recurrent SCLC patients were simulated and randomized to compare Topotecan versus II in terms of overall survival (OAS), using Reinforcement Learning (RL) and Cox proportional hazards model. RESULTS: CAV versus Topotecan comparison showed no statistical difference in overall survival (hazard ratio (HR): 0.89, 95% CI: 0.67-1.18, P = 0.418), aligning with the original clinical trial. For the Topotecan versus II comparison, the RL framework significantly favored the II arm (mean reward points: 193.43 versus - 251.82, permutation P < 0.0001). Likewise, II arm exhibited superior median OAS compared to Topotecan arm (11.12 versus 6.30 months). HR was 0.44 (95% CI: 0.38-0.52) with P < 0.0001, in favor of II. CONCLUSION: Artificial trial results for CAV versus Topotecan matched the original trial, confirming indifference of OAS. Additionally, II yielded superior overall survival compared to Topotecan in recurrent SCLC patients. These demonstrate the potential of RL and simulation in conjunction with Cox modelling for similar studies. However, definitive conclusions necessitate a randomized clinical trial between II and Topotecan in this patient cohort.

Solving the puzzle of quality of life in cancer: integrating causal inference and machine learning for data-driven insights.

BACKGROUND: Understanding the determinants of global quality of life in cancer patients is crucial for improving their overall well-being. While correlations between various factors and quality of life have been established, the causal relationships remain largely unexplored. This study aimed to identify the causal factors influencing global quality of life in cancer patients and compare them with known correlative factors. METHODS: We conducted a retrospective analysis of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire data, alongside demographic and disease-related features, collected from new cancer patients during their initial visit to an oncology outpatient clinic. Correlations with global quality of life were identified using univariate and multivariate regression analyses. Causal inference analysis was performed using two approaches. First, we employed the Dowhy Python library for causal analysis, incorporating prior information and manual characterization of an acyclic graph. Second, we utilized the Linear Non-Gaussian Acyclic Model (LiNGAM) machine learning algorithm from the Lingam Python library, which automatically generated an acyclic graph without prior information. The significance level was set at p < 0.05. RESULTS: Multivariate analysis of 469 new admissions revealed that disease stage, role functioning, emotional functioning, social functioning, fatigue, pain and diarrhea were linked with global quality of life. The most influential direct causal factors were emotional functioning, social functioning, and physical functioning, while the most influential indirect factors were physical functioning, emotional functioning, and fatigue. Additionally, the most prominent total causal factors were identified as type of cancer (diagnosis), cancer stage, and sex, with total causal effect ratios of -9.47, -4.67, and - 1.48, respectively. The LiNGAM algorithm identified type of cancer (diagnosis), nausea and vomiting and social functioning as significant, with total causal effect ratios of -9.47, -0.42, and 0.42, respectively. CONCLUSIONS: This study identified that causal factors for global quality of life in new cancer patients are distinct from correlative factors. Understanding these causal relationships could provide valuable insights into the complex dynamics of quality of life in cancer patients and guide targeted interventions to improve their well-being.

Prospective external validation of an updated algorithm to quantify risk of febrile neutropenia in cancer patients after a cycle of chemotherapy.

PURPOSE: Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity. METHODS: We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm. RESULTS: A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use. CONCLUSION: Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.

Programmed death-1 or programmed death ligand-1 inhibitors? A meta-analysis of differential efficacy as compared to chemotherapy in advanced non-small cell lung cancer.

BACKGROUND: Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions. METHODS: For this Meta-analysis, we searched PubMed, Science of Web, "Clinicaltrials.gov" and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted. RESULTS: A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naïve (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naïve and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively). CONCLUSION: Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.

Prognostic value of ERCC1, ERCC2, XRCC1, and TP53 single nucleotide polymorphisms in patients with early-stage non-small cell lung cancer.

Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8-35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6-75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0-127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6-88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.

Is there any relation between PET-CT SUVmax value and prognostic factors in locally advanced breast cancer?

PURPOSE: To investigate the relation between PET-CT SUVmax value and prognostic factors in locally advanced breast cancer. METHODS: Data of 73 patients were retrospectively analyzed. Relations between SUVmax value, clinical stage, tumor grade and breast cancer molecular subtypes were analyzed by using one-way ANOVA and x(2) tests. Correlations between age, ki-67 scores and SUVmax were evaluated by using Pearson's correlation test. A p value <0.05 was considered statistically significant. RESULTS: Median SUVmax values for clinical stages 1, 2 and 3 were 5 (range 2.1-4.1), 10.6 (range 2.9-19.6), and 12.2 (range 3.2-23.3), respectively. Statistically significant difference was noticed between stage 1 and 2 (p=0.014) and stage 1 and 3 (p=0.001). Median SUVmax values of triple negative, luminal A, luminal B and non-luminal HER2 positive groups were 14.4 (range 6.6-23.3), 8.2 (range 2.1-18.2), 10.1 (range 3.5-19.6), and 14 (range 4.1-22.9), respectively. Statistically significant differences were noticed in SUVmax values between triple-negative and luminal A groups (p=0.005) and between non-luminal HER2 positive and luminal A groups (p=0.02). Median SUVmax values of grade 1, 2 and 3 were 5.7 (range 2.1-18.2), 9.5 (range 2.2-21.3), and 11.6 (range 3.5-23), respectively. Statistically significant difference was noticed only between SUVmax values of grade 1 and 3 (p=0.035). There was negative correlation between age and SUVmax value (r=-0.23, p=0.047) and positive correlation between ki-67 and SUVmax value (r=0.43, p=0.016). CONCLUSION: There were significant positive relations between PET-CT SUVmax value and clinical stage, tumor grade, and certain breast cancer molecular subtypes (triple-negative and non-luminal HER2 positive groups. Moreover, positive correlation was found between SUVmax value and ki-67 and negative correlation between SUVmax value and age.

Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.

PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC. METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities. CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

A cross-sectional survey of the diagnosis and management of bone metastasis in breast cancer patients in Turkey.

PURPOSE: This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines. METHODS: This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0 ± 11.9 years) were analyzed. RESULTS: Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel + capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were >95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey. CONCLUSIONS: The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases.

The Optimal Treatment Modality in Patients with T4N2M0 Non-Small Cell Lung Cancer: The Best Choice May Be Definitive Chemoradiotherapy Followed by Consolidation Chemotherapy.

BACKGROUND: Stage IIIB non-small cell lung cancer (NSCLC) consists of T4N2M0 and TXN3M0 NSCLC. In the present study, we aimed to evaluate the efficacy of different treatment strategies on the survival of patients with radiologically confirmed T4N2M0 NSCLC. METHODS: A total of 145 patients were evaluated in three groups according to the treatment protocol: induction chemotherapy followed by chemoradiotherapy (induction group); chemoradiotherapy (CRT group), and chemoradiotherapy followed by consolidation chemotherapy (consolidation group). The groups were compared regarding survival. RESULTS: The median progression-free survival (PFS) was 10.9, 10.8 and 17.1 months for the induction, CRT and consolidation groups, respectively (p = 0.021). The median overall survival (OS) was 17.6, 13.8 and 25.2 months for the induction, CRT and consolidation groups, respectively (p = 0.001). CONCLUSIONS: The patients with T4N2M0 NSCLC who were treated with chemoradiotherapy followed by consolidation chemotherapy had the best outcome in terms of PFS and OS.

Use of chemotherapy at the end of life in Turkey.

BACKGROUND: An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life. METHODS: Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected. RESULTS: Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, 'newly diagnosed' patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision. CONCLUSION: In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

Yttrium-90 radioembolization in patients with unresectable liver metastases: determining the factors that lead to treatment efficacy.

INTRODUCTION: Locoregional treatments, such as radioembolization, can be used to treat patients with unresectable liver metastases. We aimed to determine the progression-free survival and factors that predict survival of patients with liver metastases whose response to selective internal radiation therapy (SIRT) with Y-90 was assessed by positron emission tomography-computed tomography (PET-CT). PATIENTS: Our study included 78 liver cancer patients who were treated with Y-90 radioembolization. RESULTS: The post-treatment response rates were as follows: 7 patients (9%) had stable disease (SD), 26 patients (33.3%) had a partial response (PR), 4 patients (5.1%) had a complete response (CR). The median hepatic progression-free survival (HPFS) was 4.4 months while median overall survival was 10.1 months. Univariate analysis revealed that HPFS is significantly affected by international normalized ratio (INR) levels and age (Hazard Ratio(HR)=0.54 (95%CI:0.30-096), P=0.034, HR=1.03(95%CI:1.00-1.05), P=0.051). However, only INR levels retained significance with multivariate analysis (HR=0.53 (95%CI:0.30-0.93), P=0.028), while age had limited significance (HR =1.02 (95% CI:1.00-1.05), P=0.051). CONCLUSIONS: We determined that Y-90 radioembolization is effective as a salvage therapy in patients with predominant liver metastases. For the first time, we showed that age and INR values reflecting the functional hepatic reserve can be used as positive predictive factors for HPFS.

Prolonged progression-free survival with maintenance metronomic oral cyclophosphamide and etoposide treatment in macroscopic residual disease or recurrent/advanced stage ovarian cancer.

PURPOSE: In ovarian cancer permanent remission may be provided with optimal cytoreductive surgery and adjuvant chemotherapy. However survival is short in patients with residual macroscopic disease after surgery or recurrent ovarian cancer. Applicable maintenance therapies with low toxicity are required to prolong progression-free survival (PFS) for patients with no curative treatment options. In this study, we investigated the effect of maintenance metronomic oral cyclophosphamide and etoposide (CE) in ovarian cancer patients with post operative residual or recurrent disease. METHODS: Forty five patients that received metronomic oral CE (cyclophosphamide 50 mg/daily and etoposide 50 mg for 1-5 days, every 21 days) as maintenance therapy for residual disease due to incomplete surgical resection or recurrent advanced-stage ovarian cancer were evaluated. The time between the beginning of oral CE and disease progression was also evaluated. RESULTS: The mean patient age was 58 years, the vast majority had serous adenocarcinoma (78%) and received a mean of 2 (range 1-4) lines of various intravenous regimens for postoperative residual or recurrent disease. Mean duration of oral CE was 11.3 months (range 2.9-29). Median PFS was 10.3 months (range 7.9-12.8). Only 5 patients discontinued treatment due to intolerance and grade 3-4 toxicity was recorded in 3 patients (7%). CONCLUSION: Maintenance metronomic oral CE treatment was found effective, minimally toxic and sustainable in patients with macroscopic residual or recurrent advanced-stage ovarian cancer. However, randomized and placebo-controlled well designed studies are required.

Evaluation of brain metabolism using F18-FDG PET/CT imaging in patients diagnosed with lung cancer.

OBJECTIVES: Brain imaging of regional metabolic changes in cancer patients can provide insights into cancer biology. We aimed to detect regional metabolic changes in the brains of untreated lung cancer patients without brain metastases using 2-deoxy-2-[18F]fluoroglucose PET/computed tomography. METHODS: The study included 44 lung cancer patients and 17 non-cancer patients as controls. Standardized uptake value (SUV) mean values of 68 different brain regions were recorded, and their ratios to whole brain and brainstem SUVmean were calculated. RESULTS: Comparisons between the groups showed significant reductions in the frontal lobe, inferior temporal gyrus, and right cingulate and paracingulate gyrus ratios in the patient group. Conversely, the right nucleus caudatus and right pallidum ratios were elevated. Correlation analysis with total lesion glycolysis (TLG) revealed positive correlations in the basal ganglia, right insula, amygdala, and right hippocampus ratios. Negative correlations were observed in the left frontal lobe and some temporal and parietal regions. CONCLUSIONS: While most brain regions showed reduced metabolism, potentially due to tumor-brain glucose competition, others were preserved or positively correlated with TLG, suggesting a link to poor prognosis. The reduced metabolism in the frontal lobe might be associated with depression and cognitive decline in cancer patients.

Hope in people with cancer: a multivariate analysis from Turkey.

AIM: The study was planned to determine the hope levels of people with cancer and the variables affecting hope. BACKGROUND: Hope is essential for patient well-being and positively correlated with improved coping skill. DESIGN: A descriptive and exploratory design. METHODS: The study sample included 240 consecutive patients treated with chemotherapy and attending the Day Chemotherapy Unit of a University Hospital in Turkey. The study was conducted between December 2009-January 2010. Personal Information Form and Herth Hope Scale were used for data collection. The determinants and subscales of hope were evaluated with univariate and multivariate regression analyses. RESULTS: These mean scores showed high levels of hope among the patients included in the study. It was found that net family income, knowledge level about the disease, feeling of improvement, perception of satisfactory family support by the patient, mouth ulcers, feeling anxious or worried and presence of fear were independently related with the total hope score. CONCLUSIONS: The study results showed high levels of hope among the participating patients. It is concluded that physical, financial and psychological well-being and information and support needs are directly and independently related with hope in people with cancer. These findings support the need for clinicians to continue to practise and implement hope fostering/hindering interventions among their patients.

The optimal upfront therapy in metastatic hormone-sensitive prostate cancer: A network meta-analysis.

Background: Prostate cancer (PC) is one of the most common cancer types in men. In addition to androgen-deprivation therapy (ADT), new generation agents have provided survival advantages to patients with metastatic hormone-sensitive PC (mHSPC). In this analysis, we aimed to determine the most effective approach for treating and suppressing mHSPC using network meta-analysis (NMA). Materials and Methods: A total of 10 trials investigating different treatment modalities were conducted using NMA. The analysis was performed for all mHSPC cases as well as for low- and high-volume and docetaxel-naive subgroups. Results: In combination with ADT, abiraterone acetate (AA) in the general-population and high-volume-disease subgroups, and enzalutamide in docetaxel-naive and low-volume-disease subgroups have the highest probability of being the best treatment modalities in terms of overall survival. In addition, in the low-volume and docetaxel-naive settings, enzalutamide was superior to ADT (hazard ratio [HR] = 0.429, 95% CrI: 0.258-0.714 and HR = 0.533, 95% CrI: 0.375-0.756, respectively). In addition, in the high-volume and general-population settings (all trials and cases), AA was superior to ADT (HR = 1.568, 95% CrI: 1.378-1.773 and HR = 1.164, 95%CrI: 1.348-1.924, respectively). Conclusion: The volume status based on the CHAARTED trial should be taken into account to determine an appropriate treatment strategy for mHSPC. AA plus prednisone in high-risk and high-volume-mHSPC patients and enzalutamide in low-volume-mHSPC patients could be favorable options in combination with ADT. Depending on the patient's tolerance, in high-volume mHSPC, docetaxel, or apalutamide in combination with ADT could be alternatives for AA, whereas in the low-volume mHSPC, local radiotherapy plus ADT or ADT alone could be utilized in place of enzalutamide.

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis.

Background: Small-cell lung cancer (SCLC) has a poor prognosis. For the last 30 years, first-line systemic treatment has remained unaltered. After the integration of immunotherapy, a new first-line gold standard, atezolizumab in combination with carboplatin plus etoposide, was approved in extensive-disease SCLC (ED-SCLC) in 2019. Materials and Methods: First-line randomized controlled studies that investigated anti-programmed cell death protein 1 (PD-1)/PD-1 ligand-1 (PD-L1) and anti-T-lymphocyte-associated protein 4 (CTLA-4) agents in combination with platinum plus etoposide (EP) were scoured. A total of six studies (two - anti-CTLA-4 and four - anti-PD1/PD-L1) were included and classic and network meta-analyses (NMAs) were performed. Results: Fixed model for overall survival (OAS) in the PD-1- or PD-L1-treated subgroup yielded a hazard ratio (HR) of 0.746 with a 95% confidence interval (CI) =0.662-0.840 and in the CTLA-4-treated subgroup a HR of 0.941 with a 95% CI = 0.816-1.084 for the immune therapy + chemotherapy versus chemotherapy comparison (CTLA-4-based versus PD-1- or PD-L1-based groups' comparison of OAS effect Q = 6.05, df = 1, P = 0.014). NMA showed that all chemotherapy + immunotherapy combinations were equally potent and more efficient than PE in terms of OAS and progression-free survival (PFS). Rank probability plots demonstrated nivolumab + EP as the most probable effective treatment modality in terms of OAS and PFS. Conclusion: The usage of anti-PD1/PD-L1 immunotherapy agents results in significant OAS advantage, and anti-PD1/PD-L1 agents are superior to anti-CTLA-4 approach in combination with platinum plus etoposide regimen in ED-SCLC.

Prognostic Significance of Adipose Tissue Distribution and Metabolic Activity in PET/CT in Patients with Metastatic Colorectal Cancer.

PURPOSE: In this study, we aimed to evaluate the prognostic significance of adipose tissue distribution and metabolic activity in PET/CT to predict survival in patients with metastatic colorectal cancer (mCRC). METHODS: The volume, density (HU), and FDG uptake (standardized uptake value (SUV)) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and maximum FDG uptake of the tumor tissue were measured. Subcutaneous adipose tissue of volume-to-density ratio (SAT ratio) was calculated. RESULTS: The median OS for the patients with SAT ratio value < -1.1 and ≥ -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). During follow-up, 69 patients experienced disease progression. The median progression-free survival (PFS) was 11.03 months (95% CI: 9.11-12.95). Median PFS for patients with tumor SUV max value < 11.5 and ≥ 11.5 were 9.2 (95% CI 7.25-11.27) and 12.6 (95% CI 10.02-15.27) months, respectively (p = 0.14). Forty-eight patients received bevacizumab therapy. VAT SUV mean (HR: 0.09; 95% CI 0.01-0.52, p = 0.008) was significantly associated with PFS in patients receiving bevacizumab. SAT ratio was the significant parameter for the OS (HR: 0.58; 95% CI 0.33-1.01, p = 0.05) and PFS (HR: 1.99; 95% CI 1.02-3.91, p = 0.043). CONCLUSIONS: SAT ratio was an independent prognostic factor for survival in patients with mCRC. Higher SAT volume is correlated with longer survival in mCRC patients.

The correlates of benefit from neoadjuvant chemotherapy before surgery in non-small-cell lung cancer: a metaregression analysis.

BACKGROUND: Although neoadjuvant chemotherapy (NCT) is widely used, it is not clear which subgroup of locally advanced non-small-cell lung cancer (NSCLC) patients should be treated with this approach, and if a particular benefit associated with NCT exists. In this study, we aimed to investigate the potential correlates of benefit from NCT in patients with NSCLC. METHODS: All randomized clinical trials (RCTs) utilizing a NCT arm (without radiotherapy) versus a control arm before surgery were included for metaregression analysis. All regression analyses were weighed for trial size. Separate analyses were conducted for trials recruiting patients with different stages of disease. Previously published measures of treatment efficacy were used for the purpose of this study, regardless of being published in full text or abstract form. RESULTS: A total of 14 RCTs, consisting of 3,615 patients, were selected. Histology, stage, various characteristics of the NCT protocol, and different trial features including trial quality score were not associated with the benefit of NCT. However, in trials of stage 3 disease only, there was a greater benefit in terms of reduction in mortality from NCT, if protocols with three chemotherapeutics were used (B = -0.18, t = -5.25, P = 0.006). CONCLUSIONS: We think that patients with stage 3 NSCLC are served better with NCT before surgery if protocols with three chemotherapy agents or equally effective combinations are used. In addition, the effect of neoadjuvant chemotherapy is consistent with regard to disease and patient characteristics. This finding should be tested in future RCTs or individual patient data meta-analyses.

Effects and permanency of the training program "communication with cancer patients" on the opinions of students.

Learning to develop the doctor-patient relationship is very important in the treatment of patients with cancer. We aim to train our students in the early years of study about this subject with a course on the patient-doctor communication, prepared for third year students. One hundred fifty-four third year students participated in our study during the 2006-2007 academic years. The same questionnaire was given to the students in the 2009-2010 academic year; their sixth year of study. The rate of return for the questionnaire is 88.7%. Based on this study, we have the opinion that the training given in the third year is beneficial; however, the efficacy of the training diminishes with the advancing years, and therefore, the length of this training should be increased in the upper classes and additional hours should be added.

Prognostic value of HPV DNA in Urothelial Carcinoma of the Bladder: A Preliminary Report of 2-Year Follow-up Results.

PURPOSE: The association between the human papillomavirus (HPV) and anogenital carcinomas is well established. However, despite its anatomic adjacency, the relationship between HPV and urothelial carcinoma of the bladder (UCB) is less clear. Recent meta-analysis and case-control studies demonstrated a significant relationship between the presence of HPV DNA and UCB. The aim of this clinical study was to compare the 2-year follow-up results of HPV-positive and HPV-negative UCB patients to evaluate the prognostic value of HPV DNA positivity in UCB. METHODS: The study included patients with stage pTa and pT1 UCB who underwent polymerase chain reaction (PCR) analysis of HPV DNA between January 1 and November 30, 2018. Based on their PCR results, 19 HPV-positive and 38 HPV-negative UCB patients who had regular follow-up in our clinic were evaluated in terms of tumor recurrence and disease progression over a 2-year follow-up period. RESULTS: There was no significant difference between the groups in terms of age, follow-up time, smoking, or tumor grade (P= .576, P= .368, P= .080, and P= .454). Tumor recurrence was observed at least once in 47.3% (n=9) of the 19 HPV-positive patients and 36.8% (n=14) of the 38 HPV-negative patients (P= .445). There was no difference in disease progression between the groups during follow-up. CONCLUSION: In our sample of UCB patients, the presence of HPV DNA was associated with a trend toward higher recurrence rate during the 2-year follow-up, though the difference was not statistically significant. No difference in disease progression was observed based on HPV DNA positivity.