A current comprehensive role of immune-checkpoint inhibitors in resectable non-small cell lung cancer: A narrative review.

OBJECTIVE: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC). DATA SOURCES: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC. DATA SUMMARY: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress. CONCLUSION: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches.

Tamoxifen related chorioretinal structural changes.

PURPOSE: To evaluate the vascular structure of the choroid and each retinal layer in patients with breast cancer on tamoxifen therapy and compare them with healthy subjects. MATERIALS AND METHODS: 124 eyes of 62 patients with breast cancer who were on tamoxifen therapy (group 1) and 80 eyes of 40 healthy controls (group 2) were included in this prospective cohort study. The structure of the choroid was evaluated using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) and choroidal binarisation. Spectral-domain OCT (SD-OCT) was performed to analyse the peripapillary nerve fibre layer thickness (pRNFL) and each retinal layer thickness. A subgroup analysis was performed based on chemotherapy history in Group 1. All parameters were compared between Group 1 and the healthy controls and between the subgroups of Group 1. RESULTS: The subfoveal choroidal thickness and temporal and nasal directions were increased in Group 1 when compared with Group 2 (p < 0.05, each comparison). Choroidal vascularity index was significantly decreased in Group 1 compared with Group 2 (63.15 ± 3.11% and 65.37 ± 4.63%, p < 0.001). There were no significant differences in each retinal layer, pRNFL thickness, and choroid structural parameters between the subgroups of Group 1. CONCLUSIONS: Increased choroidal thickness may be the initial finding of subclinical tamoxifen-induced retinopathy. Patients with breast cancer undergoing tamoxifen therapy may be screened prior to tamoxifen therapy and followed during treatment by SD-OCT.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

[Clinical features of the ALK-mutant non-small cell lung cancer patients who received first-line alectinib treatment]. / Birinci basamak alektinib tedavisi alan ALK mutasyonu pozitif akciger kanseri hastalarinin klinik özelliklerinin degerlendirilmesi.

INTRODUCTION: Lung cancer is the most common cancer type and the leading cause of cancer-related mortality worldwide. The positivity rate of the anaplastic lymphoma kinase (ALK) mutation in non-small cell lung cancer (NSCLC) patients has been reported as 3-7%. This study aimed to investigate the pathological, clinical and demographic characteristics of ALK-mutant NSCLC patients who received first-line alectinib as a tyrosine kinase inhibitor in two different centers. MATERIALS AND METHODS: The study was performed at the Medical Oncology Departments of Ankara City Hospital and Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital. Patients diagnosed with ALK-mutant NSCLC and received alectinib treatment as a first-line tyrosine kinase inhibitor were enrolled to study and retrospectively analyzed. RESULT: A total of 38 patients (15 males, 23 females) were included in the study. Median age was 56.5. 55.3% of the patients were non-smokers. All of the patients had adenocarcinoma histology. Thirty-four patients (89.5%) were metastatic. Brain metastasis was detected in 44.7% of the patients. Thirty-three patients (86.8%) were using alectinib in first-line treatment. The remaining five patients were seen to have received at least one course of chemotherapy before. The objective response rate was 78.9% with alectinib treatment. The percentage of the patients who experienced at least one side effect was 34.2% and serious side effects were 7.9%. After median 9.5 months follow-up, median progression-free survival (PFS) was not achieved. 24-month PFS was 67% and 24-month overall survival was 84%. CONCLUSIONS: Our results were compatible with previous studies in terms of the clinical, pathological and demographic features of the patients with ALK mutation. We observed that the majority of patients were non-smokers, relatively young, and female patients. The objective response rate and survival results were similar with phase 3 studies.

Neutrophil-lymphocyte ratio as a prognostic factor for survival in patients with advanced renal cell carcinoma (Turkish Oncology Group Study).

BACKGROUND: To describe the prognostic value of neutrophil-lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma. METHODS: We retrospectively analyzed 331 patients. The cut-off value of neutrophil-lymphocyte ratio was specified as "3" which is mostly close-and also clinically easily applicable-to the median neutrophil-lymphocyte ratio level of our study group. High group is identified as neutrophil-lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil-lymphocyte ratio ≤3 (n = 163). RESULTS: A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil-lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37-0.65), p < 0.001). CONCLUSION: In conclusion, the pre-treatment value of elevated neutrophil-lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients.

The association of clinicopathologic features and peripheral blood parameters with high PD-L1 expression in non-small cell lung cancer.

INTRODUCTION: Programmed death ligand 1 (PD-L1) is a marker that widely used for prediction of response to immunotherapy. Dynamic alteration of PD-L1 expression are the major problems for reflection of the actual status of the PD-L1. So, we aimed to investigate the factors that may be associated with PD-L1 expression in lung cancer. MATERIALS AND METHODS: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The patients were stratified according to PD-L1 expression level as ≥ 50% and < 50%. RESULT: Totally, 217 patients were enrolled. The clinicopathologic features were similar between two groups, except the amount of cigarette consumption. Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammmotry index were found significantly lower in PD-L1 ≥ 50% (p< 0.001, p= 0.006 and p= 0.003, respectively) and also negatively correlated with PD-L1 level (rho= -0.255, p< 0.001; rho= -0.17, p= 0.013; rho= - 0.185, p= 0.006, respectively). CONCLUSIONS: According to the results of our study, peripheral blood parameters can be used to the prediction of the high PD-L1 expression and can be used for reflection of current PD-L1 expression.

Branches of ulnar artery in human fetuses: anatomical and morphometric study.

PURPOSE: This study was conducted to demonstrate morphological pattern of the ulnar artery and to evaluate morphometrically its anatomical branching pattern in human fetuses. METHODS: Branching pattern of ulnar artery was evaluated on 121 upper limbs of dissected 63 of formalin-fixed fetus cadavers with gestational age ranging from 17 to 40 weeks. In order to obtain second and third trimester data, according to their gestational age, two groups were determined. RESULTS: In 79 of all 121 upper limbs (65%) ulnar artery gave anterior and posterior ulnar recurrent arteries as separate branches. In this study frequency of presence of a median artery was 46.28% among total examined 121 upper limbs. Median arteries originated from ulnar artery (3.57%) and from the common interosseous artery (53.57%) and anterior interosseous artery (42.85%). Mean distances of the measured parameters were demonstrated according to the gestational age and differences between group I (second trimester) and group II (third trimester). No statistical difference for groups was observed for gender and between right and left sides. CONCLUSIONS: Ulnar artery shows predictable patterns during second and third trimester of fetal period and can be suitable access effective alternative for diagnostic and therapeutic coronary interventions. Persistent median artery is important variation and knowledge of its incidence is important for diagnostic difficulties and also during awareness of its injury during surgical approaches.

The results of nasopharyngeal cancer patients treated by simultaneous integrated boost technique and concomitant chemotherapy

Background/aim: To assess the efficacy and side effects of concurrent weekly chemotherapy and radiotherapy with simultaneous integrated boost (SIB) technique for nasopharyngeal cancer (NPC). Materials and methods: total of 51 consecutive patients with diagnosis of NPC were treated between February 2010 and December 2015. The median dose for PTV70 (range: 60­82) was given in 33 fractions (range: 31­35). Forty-five of the patients received concomitant weekly chemotherapy between 3­7 cycles (median 6). Eleven patients received neoadjuvant and thirty-nine patients received adjuvant chemotherapy. Results: At a median follow-up 43 months (range: 2­76) the estimated 5-year overall survival and disease-free survival were 74.6% and 62.6%, respectively. Conclusion: In radiotherapy of advanced NPC, generally a considerable amount of normal head and neck tissues might have to be irradiated in addition to gross tumor volume, involved node, and elective neck irradiation. Together with chemoradiotherapy, poor oral hygiene and inadequate nutritional support result in excessive morbidity. Despite loco-regional success of concurrent chemoradiotherapy, distant metastasis is still the major pattern of treatment failure in the intensity modulated radiotherapy era. We need to improve our adjuvant chemotherapy regimens or develop new drugs.

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.

Endoscopic third ventriculostomy: A historical review.

BACKGROUND: Endoscopic third ventriculostomy (ETV) has become one of the most common neuroendoscopic procedures. METHODS: In this article, we will review the major milestones in the history of ETV development from its early use by Walter Dandy to the techniques currently employed with advanced technology. CONCLUSIONS: ETV has become an important technique in the armamentarium of the neurosurgeon. From a meager beginning with few applications, our knowledge of long-term outcomes has evolved. ETV has a rich history and more recently, has had a renewed interest in its use. Our current understanding of its indications is growing and is based on a century of development through trial and error.

Topographical anatomy of cricothyroid membrane and its relation with invasive airway access.

Cricothyroidotomy is a surgical procedure involving penetration through the skin and cricothyroid membrane to maintain airway patency during life-threatening emergency conditions. Complications such as bleeding and laryngeal stenosis can result from it. Our aim in this study was to identify the anatomical structures located on the membrane and to ascertain whether there is a safe area on the membrane for this procedure. Thirty larynx specimens fixed with 10% formaldehyde in the Department of Anatomy were dissected. The cricothyroid artery, the cricothyroid vein, the common artery and vein formed by the cricothyroid vessels, the pyramidal lobe of the thyroid gland and lymph nodes were observed on the membrane. The cricothyroid membrane was divided into four quadrants and the most common locations of these anatomical structures on the membrane were recorded. The cricothyroid artery and vein were located on the upper half of the membrane, the common vein was found in the midline, coursing to the thyroid gland, and the lobus pyramidalis and lymph nodes were located on the left side of the midline. Overall, the anatomical structures were mostly located on the upper half and lower left quadrant of the cricothyroid membrane. Thus, the lower right quadrant seems safer for invasive procedures such as needle cricothyroidotomy or other cannulation techniques. Needle puncture or cannulation through the lower right quadrant of the cricothyroid membrane will injure fewer anatomical structures so there should be fewer complications due to degradation of the vascular supply to this region. Clin. Anat. 29:949-954, 2016. © 2016 Wiley Periodicals, Inc.

Analysis of the tortuosity of the internal carotid artery in the cavernous sinus.

BACKGROUND: The morphology of the internal carotid artery at the skull base is important in radiologic interpretation, surgery, and more recently, endovascular interventional and diagnostic procedures. Therefore, a thorough knowledge of the shape of the carotid siphon can be important in the clinical realm. METHODS: In this study, we evaluated the shape of the carotid siphon from a lateral perspective on cerebral angiography. These shapes were then correlated to the Lang and Reiter classification. RESULTS: Types A, B, and C were distributed as follows: type A 12 (30%), B 16 (40%), 12 (30%). There was no significant difference (p > 0.05) in patient ages between the three types (type A 54.6 ± 14.2 years, type B 55.1 ± 14.9 years, and type C 52.7 ± 16.9 years). Normalized for gender disproportion, there was no significant gender predominance for any type (type A female:male = 1.4:1; type B female:male = 1.1:1; type C female:male = 0.7:1). CONCLUSIONS: Such a classification scheme with additional application in another group might be of use to future studies aimed at the morphology of the cavernous part of the internal carotid artery.

Blood supply of the terminal part of the external branch of the superior laryngeal nerve.

PURPOSE: The external laryngeal nerve (ELN) carries motor fibers to the cricothyroid and inferior pharyngeal muscles. Damage to the nerve may cause symptoms such as a monotone voice. One reason for these symptoms may be nerve injury due to inadvertent stretching, ligation or transaction of the nerve during the dissection of the superior pole of the thyroid gland. We hypothesized a new reason for the symptoms, an insufficient arterial blood supply to the nerve, and investigated this hypothesis. METHODS: From 36 larynges, 52 sides (26 right and 26 left) were dissected under a surgical Zeiss-OpM1 microscope. RESULTS: The arterial branch to the external branch of the superior laryngeal nerve originated from the posterior glandular branch of the superior thyroid artery in 26 (50%) sides, from the anterior glandular branch in 23 (44.23%) sides, from its trunk on one (1.92%) side, from the infrahyoid branch on one (1.92%) side and from the bifurcation of the superior thyroid artery at the level of separation of the anterior and posterior glandular branches on one (1.92%) side. CONCLUSION: Devascularization of the ELN may lead to dysfunction, so this nerve's varied blood supply should be kept in mind when invasive procedures are performed in this region.

End-of-study results of Turkish gastric cancer patients from the global REGATE study.

PURPOSE: Registry of Gastric Cancer Treatment Evaluation (REGATE) study was an international, prospective study including over 10000 patients from 22 countries, designed to describe the pattern of care in gastric cancer globally. The aim of this study was to summarize the data of the Turkish arm and compare them with the global results. METHODS: Ten centers from Turkey took part in the REGATE registry. Between 2004 and 2008, 395 patients (median age, 60 years; range, 18-91, 67.6% men) with newly diagnosed primary adenocarcinoma of the stomach were followed at initial visit and 8-10 months later, at the time of treatment completion. Data on patient demographics, medical history, histopathology, cancer stage, planned and realized treatments was prospectively collected. Data processing and analysis were conducted centrally. RESULTS: In Turkey, the majority of patients were diagnosed at an advanced stage, while the rate of surgery was lesser compared with the rest of the world. Realized treatment included more palliative-only therapy than initially planned (63.3%), while no therapy was recommended in 21.8%. Surgery involved total gastrectomy (46.3%) or distal subtotal gastrectomy (51.9%), with 87% R0 resection, 51.0% D1 and 44.9% D2 lymph node dissection. Combination chemotherapy was administered in more than half of the patients receiving palliative therapy (57.9%). Chemoradiotherapy was used in 66.7% of the cases receiving adjuvant therapy. Radiotherapy was applied to 32% of the cases receiving palliative therapy. CONCLUSION: Advanced stage gastric cancer is highly prevalent in Turkey. Increasing public awareness and implementing screening programs in high risk groups may help identify gastric cancer at earlier stages.

Do metastatic volumes measured in breast cancer patients with bone metastases correlate with the numbers of skeletal and extraskeletal events?

OBJECTIVES: The study aimed to investigate the relationship between metastatic volume measurement, skeletal-related events, and survival in women diagnosed with breast cancer and bone metastases. PATIENTS AND METHODS: This retrospective study was conducted with 82 female breast cancer patients (mean age: 53±14.3 years; range, 23 to 87 years) diagnosed, treated, and followed up between January 2005 and December 2019. The collected data included information on metastasis sites and the presence of skeletal-related events. Metastatic volume was measured in two ways: the number of metastases (high to low) and their localization (the first, second, and third groups). The first group consisted of vertebrae, ribs, sternum, and calvarial bones; the second group included scapula, clavicle, proximal humerus, and proximal femur regions; the third group consisted of femur and humerus diaphyseal and distal regions, as well as metastasis regions in other long bones. RESULTS: Sixty-three (76.8%) patients were diagnosed with ductal carcinoma. Half of the patients had bone metastases at the time of initial diagnosis, while 62 (75.6%) experienced skeletal-related events, with at least three events occurring in 30 (36.6%) patients. Bone pain was the most common skeletal-related event. No correlation was found between metastatic volume measurement based on the localization of bone metastases and the number of bones and the occurrence of skeletal-related events (p>0.05 for each). Patients' survival time spanned from one to 231 months (median: 56.8 months) from their first diagnosis. Patients with high metastatic volume, those in the third group, those whose pelvis and lung were involved, and elderly patients had a shorter survival time (p<0.05 for each). CONCLUSION: The study indicates that measuring metastatic volume may be a critical factor in evaluating the survival of breast cancer patients with bone metastases. Future prospective and randomized controlled studies can explore the potential of this measurement to create practical clinical tools.