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Background Interstitial lung disease interstitial lung disease is a group of respiratory diseases that causes progressive fibrosis. Many of the recently approved oncology drugs are associated with the development of interstitial lung disease as an adverse event. We report an alpelisib-induced interstitial lung disease in a patient with advanced breast cancer. Case report A 65-year-old breast cancer patient who had multiple bone metastases and had been previously treated with letrozole and ribociclib, started alpelisib and fulvestrant combination upon the development of liver metastases. Her past medical history was not significant except the history of hypertension. She developed fatigue and progressive dyspnea 3, 5 months after starting alpelisib and was hospitalized due to rapidly deteriorating hypoxia within 2–3 days. Management and outcome Naranjo Algorithm calculated score was 4 (probable Adverse Drug Reaction). Her thoracic computed tomography and angiography scan were consistent with interstitial infiltrate ground-glass appearance. She had no fever. Her workup for COVID-19 (coronavirus disease), other respiratory infectious agents, and pulmonary embolism was negative. There was a rapid clinical and radiologic response to corticosteroid therapy within one week. She was discharged from the hospital with a tapered steroid dose and complete resolution of her lung infiltrations. Alpelisib was discontinued despite radiological partial response in her liver metastases and a decline in her tumor marker. Discussion Drug-induced interstitial lung disease is usually a diagnosis of exclusion, difficult to identify particularly during the COVID-19 pandemic for patients with cancer. Differential diagnosis includes infectious pneumonia, radiation pneumonitis, diffuse alveolar hemorrhage, pulmonary edema, and pulmonary lymphangitic metastasis.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Aim: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). Patients and methods: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. Results: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. Conclusion: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.

Triple negative breast cancer (TNBC) is an aggressive subtype with frequent chemotherapy resistance. In recent years, advances in immunotherapy have yielded promising new therapeutic strategies for the treatment of TNBC; studies evaluating immune check point inhibitors (ICIs) in combination with chemotherapy have shown encouraging results in both early and advanced stages of disease. Atezolizumab plus nab-paclitaxel resulted in improved progression-free survival (PFS) and overall survival (OS) compared to nab-paclitaxel alone in patients with programmed death-ligand 1-positive (PD-L1+) metastatic TNBC (mTNBC). However, atezolizumab plus paclitaxel did not improve outcomes. Pembrolizumab plus chemotherapy improved PFS compared to chemotherapy alone in patients with PD-L1+ mTNBC, and follow-up for OS is ongoing. The addition of pembrolizumab and atezolizumab to neoadjuvant chemotherapy increased pathologic complete response rates, regardless of PD-L1 status, and event-free survival is pending. Several other combinations of ICIs with targeted agents are under investigation to enhance the host immune response and are discussed in this review. TNBC has a poor prognosis with limited treatment options. Recent studies have demonstrated encouraging results by adding ICIs to chemotherapy, although optimal combinations remain to be defined. In this review, we highlight advances in TNBC treatment including ICIs and targeted agents and also discuss future directions.

Background: CTCs are detectable in approximately 50% of pts with metastatic breast cancer, and elevated CTC levels are an independent negative prognostic factor. CTCs have been shown to play a valuable role in predicting outcomes in pts with ABC treated with chemotherapy or endocrine therapy. This phase II trial was conducted to evaluate the clinical benefit (CB) of pazopanib, a VEGF receptor tyrosine kinase inhibitor (TKI) combined with nonsteroidal aromatase inhibitors (NSAIs) in pts with ABC resistant to NSAIs. As an exploratory analysis, we hypothesized that CTC levels might be correlated with response to pazopanib plus endocrine therapy. Methods: Eligibility included postmenopausal women with hormone receptor positive (HR+) ABC and progressive disease after at least one month of NSAIs. Treatment was pazopanib 800 mg/day plus either letrozole or anastrozole. The primary endpoint was clinical benefit rate at 12 weeks (CBR12, wks). Secondary endpoints included progression free survival (PFS), safety, and the impact of pazopanib and NSAI on CTCs. A CBR of 20% was considered a clinically meaningful comparison to the expected CBR of Results: 32 pts were enrolled; 28 are evaluable for study endpoints. The median age was 58 years (range: 41-77). Pts were heavily pre-treated, with a median of 2 prior hormone therapies (range 1-6) and 1 prior chemotherapy (range 0-8). 8 pts (28.6%) stopped treatment due to adverse events, and 6 pts progressed before wk 12. CBR12 was 46.4% (12 SD, 1 PR), and CBR24 was 25% (5 SD, 2 PR). Safety has been presented (ASCO 2020). Median PFS was 20 wks, and median PFS for pts with CBR12 was 24 wks. Five (22%) of 23 pts with CTC data were CTC-positive (5 CTC/7.5 mL). There was no significant association between CBR12 and CTC status at baseline, or between CBR12 and change in CTC status (baseline to 4 wks after initiation of treatment). 7 pts had non-CBR12 and CTC data; 4 pts (n=4/7; 57%) were CTC positive at either baseline, week 4 or both. 11 pts had CBR12 and CTC data; all patients were CTC negative at baseline and remained negative at 4 wks. 7 pts had PFS >6 months (24, 32, 36, 36, 48, 184 and 274 wks), and 6 had CTC data: all were CTC-negative at baseline and 4 wks, then remained negative at 12 wks. Based on baseline values only, CTC-positive pts had a shorter median PFS compared to CTC-negative pts, but the difference was not statistically significant (11 wks vs 14 wks, p=0.18). Persistently CTC negative patients had significantly longer PFS compared to patients who were CTC positive at any time during study treatment (36 wks vs 11 wks, p=0.01). Conclusions: The addition of pazopanib to NSAIs resulted in a CBR12 of 46.4%, and a CBR24 of 25% in pts with heavily pre-treated ABC resistant to NSAIs. These results support clinical efficacy of antiangiogenic TKI in HR+ ABC and suggest benefit in hormone resistant disease. Consistently negative CTCs correlated with response and response duration. PFS was significantly longer in patients who were consistently CTC negative, further defining the prognostic role of CTCs in HR+ ABC. (NCT01466972) Citation Format: Ozge Gumusay, Mark Jesus M. Magbanua, Melanie C. Majure, Travis Deal, Jonathan R. Renslo, Chiara A. Wabl, Michelle E. Melisko, A. Jo Chien, Andrei Goga, Mark M. Moasser, John W. Park, Jimmy Hwang, Hope S. Rugo. Circulating tumor cell (CTC) enumeration in a phase II trial of pazopanib in addition to endocrine therapy in patients with hormone resistant advanced breast cancer (ABC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-19.

Opinion statement The treatment of renal cell carcinoma (RCC) is one of the great success stories in the field of oncology, which was revolutionized with the development of therapies aimed at disrupting crucial pathways. Tumor biology of RCC has provided insight into the disease through elucidation of the role of vascular endothelial growth-factor (VEGF) and the mammalian target of rapamycin (mTOR). Targeted agents against VEGF and mTOR, as well as agents targeting relevant immunomodulatory pathways, have shown clinical benefit for advanced disease. The targeted agents are highly effective in achieving a response and survival, particularly in high-risk patients. These include the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) axitinib and cabozantinib, and programmed cell death 1 protein (PD-1) immune checkpoint inhibitors (ICI) nivolumab and pembrolizumab. There is a wealth of evidence investigating different therapeutic options and combinations for first-line treatment of advanced RCC including the CheckMate 214 study, KEYNOTE-426, JAVELIN Renal 101, and CheckMate 9ER. Dual ICI and combination agents targeting the programmed cell death protein 1/programmed cell death protein ligand 1 (PD1/PDL1) and VEGF, began to demonstrate superiority over previously accepted standards in advanced clear-cell RCC. Data from a number of clinical studies are available to help physicians with evidence-based decisions for the sequence of second-line and future treatments for patients with progressive RCC. In this review, we focus on essentials for clinicians treating patients with clear-cell RCC.

Hormone receptor (HR)-positive, HER2-negative tumors represent the most common form of metastatic breast cancer (MBC), and endocrine therapy has been the mainstay treatment for several decades. Recently, a novel drug class called CDK4/6 inhibitors in combination with endocrine therapy have remarkably improved the outcome of patients with HR-positive, HER2-negative MBC by targeting the cell cycle machinery and overcoming aspects of endocrine resistance. Several potential cell-cycle-specific and nonspecific mechanisms of resistance to CDK4/6 inhibitors have been reported in recent studies. This review discusses potential resistance mechanisms to CDK4/6 inhibitors, the use of biomarkers to guide treatment for HR-positive, HER2-negative MBC and possible approaches to overcome resistance to CDK4/6 inhibitors.Approximately 70% of breast cancers are hormone receptor (HR)-positive. A CDK4/6 inhibitor combined with endocrine therapy is the first-line standard of care for patients with HR-positive, HER-2 negative advanced breast cancer. Markers to predict the efficacy of CDK4/6 inhibitors in HR-positive, HER2-negative advanced breast cancer are limited. In this review, we summarize the use of CDK4/6 inhibitors in breast cancer, as well as possible approaches to overcome resistance to CDK4/6 inhibitors.

Recent advances in the understanding of underlying molecular signaling mechanisms of cancer susceptibility and progression have led to an increase in the use of targeted therapies for cancer treatment. Despite improvements in survival with new treatment options in oncology, resistance to therapy is a major obstacle to the long-term effectiveness of targeted agents in metastatic cancer treatment, culminating in insensitivity to treatment and tumor outgrowth. Adaptive resistance can play an important role in primary and upfront resistance to therapy as well as in secondary or acquired resistance. By focusing on colorectal and breast tumors, we discuss how therapeutic combinations based on specific drivers of tumor biology can be used to overcome resistance. We present how monitoring tumor dynamics over time may allow early adaptation of treatment. Breast cancer is the most common malignancy in women worldwide, and the majority of these cancers are sensitive to endocrine therapy (ET) blocking the production of or response to estrogen. However, primary and acquired resistance limits efficacy. Recent combinations of agents targeted to pathways that drive tumor growth resistance with ET have resulted in remarkable improvements in disease response and control, improving survival in some settings. In this review, we summarize adaptive resistance mechanisms, approaches to combination strategies, and dynamic tumor monitoring to improve efficacy and overcome resistance. We provide examples of combination therapy to enhance the efficacy of targeted therapies in breast and colorectal tumors.

Patients with metastatic breast cancer are at high risk for developing vertebral compression fractures due to underlying bone metastases and bone density loss. Vertebral augmentation techniques including percutaneous vertebroplasty and percutaneous balloon kyphoplasty are techniques used to stabilize compression fractures and improve pain. However, rare complications from these interventions have been observed, including spinal cord compression, nerve root compression, venous cement embolism, and pulmonary cement embolism. These complications pose unique potential challenges for patients with cancer who may already have decreased lung function and potential for venous thromboembolism. In this review, we first describe the role of percutaneous vertebral augmentations in patients with metastatic cancer, with a particular focus on patients with breast cancer. Then, we describe complications of vertebral augmentation in two patients with metastatic breast cancer including long-term symptomatic and radiographic follow-up.

Liquid biopsy biomarkers, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are noninvasive diagnostics that could complement predictive and prognostic tools currently used in the clinic. Recent trials of immunotherapy have shown promise in improving outcomes in a subset of breast cancer patients. Biomarkers could improve the efficacy of immune checkpoint inhibitors by identifying patients whose cancers are more likely to respond to immunotherapy. In this review, we discuss the current applications of liquid biopsy and emerging technologies for evaluation of immunotherapy response and outcomes in breast cancer. We also provide an overview of the status of immunotherapy in breast cancer.

Oligometastatic prostate cancer (PCa) can be defined as cancer with a limited number of metastases, typically fewer than 5 lesions, and involves lesions contained within the axial versus the appendicular skeleton. Patients can present with de novo oligometastatic, oligorecurrent, or oligoprogressive PCa. Oligometastatic PCa patients demonstrate considerable improvements in survival outcomes, with a better prognosis than patients with extensive metastatic disease. However, the management of patients that present with nonsymptomatic oligometastatic PCa remains difficult. In the oligometastatic setting, the benefit of local therapies such as prostatectomy and radiotherapy on survival outcomes is an intriguing topic; however, their impact on oncological outcomes is still unknown.

Renal hucreli karsinom (RHK); eriskin yas grubunda en sik karsilasilan renal tumordur. Bununla birlikte RHK'larin yaklasik %8’inde sarkomatoid diferansiyasyon gorulmektedir. Bu diferansiyasyon oldukca agresif davranisli olup kotu prognoz ile iliskilidir. Bu calismada hematuri yakinmasi ile tani alan 44 yasindaki sarkomatoid RHK olgusu literatur bilgileri isiginda ele alinmistir .

e13049 Background: COVID-19 pandemic has placed an unprecedented burden on health care system. Patients with cancer are reported to have a higher risk of infection and a more complicated COVID-19 course. Breast cancer (BC) is the most common cancer in women in Turkey. We aimed to evaluate the clinical outcome of breast cancer patients who had a diagnosis of COVID-19. Methods: Medical records of breast cancer patients who had COVID-19 between July 2020-2021 at our center were retrospectively rewieved. We recorded pathological, clinical, treatment characteristics, and the clinical outcome of COVID-19 infection. Results: A total 82 breast cancer (BC) patients had COVID-19 between July 2020-2021. All patients were female, with a median age of 49 (43-64 years). Eighty-five % of all patients had early and 14.6% had advanced stage BC. COVID-19 had a mild clinical course in 73%, hospitalization was required in 27% of patients. Twenty-five patients who required hospitalization were discharged. Three (3,6%) patients who had heavily pretreated metastatic breast cancer, required ICU and died due to COVID-19. Metastatic disease (p 0.002) and chemotherapy within 7 days of COVID-19 diagnosis (p = 0.024) have been associated with increased mortality. Conclusions: In our breast cancer cohort, most patients had a mild COVID-19 course. Advanced disease and chemotherapy within 7 days of diagnosis were the two risk factors for increased mortality.

Objective Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. This study evaluates ezrin expression in sunitinib-treated metastatic clear cell renal cell carcinoma (ccRCC) patients and elucidates its role as a possible marker for survival. Materials and methods The expression of ezrin was measured by immunohistochemistry in 80 patients with ccRCC treated by first-line sunitinib between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. Results In multivariate analysis, liver metastasis (P = 0.018; hazard ratio [HR]: 3.707 (1.257-10.931) and overexpression of ezrin (P = 0.006; HR: 2.993 (1.373-6.523 95% confidence interval) were remained significant factors influencing OS. Overexpression of ezrin in the patients who had progressed in the first 3 months was higher than in the patients who had progressed after 3 months (P = 0.003). The median OS was longer in patients with low levels of ezrin expression (27 months) compared to patients overexpressing ezrin (12 months) (P = 0.001). Conclusion This is the first study in the literature showing that ezrin status is related with prognosis in patients with metastatic ccRCC.

Background: Endothelial nitric oxide synthase (eNOS) is essential in chronic inflammation and carcinogenesis. The association between variants in vascular endothelial growth factor (VEGF) and several cancers still remains uncertain. We studied whether there is a relation between eNOS/VEGF variants and risk of pancreatic cancer (PC). Materials and Methods: This prospective case-control study included 76 PC patients (28 women and 48 men) and 100 healthy controls. Blood samples from all participants were genotyped for eNOS variable number tandem repeat (VNTR) and VEGF insertion/deletion (I/D) variants by PCR. Results: There was a significant difference between groups for the eNOS intron 4 VNTR genotype distributions (p = 0.01). eNOS 4a/4b and 4b/4b genotypes were higher in patients with PC group compared to controls while eNOS 4a/4b genotype was more prevalent in control group than in patient group. Significant differences were observed between groups for the VEGF I/D variant genotype and allele frequencies (p < 0.00, and p < 0.00). VEGF I/D variant I/I genotype and I allele increased in patient group than controls. A statistically significant association was observed when the patients were compared with the controls according to D/D + D/I versus D/D (p < 0.00, OR: 0.094, 95% CI: 0.03-0.22). Conclusions: We provided evidence that eNOS VNTR and VEGF I/D variants might influence the development of PC. WOS:000641257000010 2-s2.0-85104532165

Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin. In this study, we aimed to evaluate the clinicopathologic characteristics, treatment outcomes, and survival of MCC cases in Turkey. Materials and methods: The patients diagnosed with MCC between 1999 and 2018 at twenty different centers in Turkey were included in the study. Patient and tumor characteristics and adjuvant and metastatis treatment outcomes were analyzed retrospectively. Results: The median age of totally 89 patients was 70 (26-93). The most common primary location was lower limbs (n = 29, 32.5%). Immunohistochemically, CK20 positivity was present in 59 patients (66.3%). Only two patients had secondary malignancy. The majority of the patients (n = 76, 85.4%) were diagnosed at the localized stage. Surgery was performed for all patients in the early stage, and adjuvant radiotherapy or/and chemotherapy was applied to 52.6% (n = 40) of nonmetastatic patients. The median follow-up was 29 months. Recurrence developed in 21 (27.6%) of the 76 patients who presented with local or regional disease. Two-year disease-free survival (DFS) was 68.1% and 5-year DFS was 62.0% for localized stage. The 5-year DFS was similar for patients receiving adjuvant treatment (chemotherapy, radiotherapy, or sequential chemoradiotherapy) and without adjuvant therapy (P > 0.05). Two-year overall survival in patients who presented with localized disease was 71.3% and 18.5% in metastatic patients (P < 0.001). In the metastatic stage, platinum/etoposide combination was the most preferred combination regimen. Median progression-free survival (PFS) in first-line chemotherapy was 7 months (95% confidence interval: 3.5-10.5 months; standart error: 1.78). Conclusions: Although MCC is rare in Turkey, the incidence is increasing. Gender, CK20 status, tumor size, lymph node involvement, and adjuvant treatment were not associated with recurrence.

Objective: Pancreatic cancer (PC) is a serious disease with poor outcomes, and its prevalence has been increasing steadily. The circadian rhythm (CR) is involved in multiple physiological events and maintains homeostasis. Alterations in the CR elevate the risk of developing cancer. The present case-control research was carried out to estimate the possible association between PERIOD2/PERIOD3 (PER2/PER3) gene variable number tandem repeat polymorphism (VNTR) variants and PC in the Turkish population. Materials and Methods: A total of 198 subjects (78 patients with PC and 120 healthy controls) were enrolled in this work. Genomic DNA was collected from peripheral blood mononuclear cells, and genotype analysis was performed using a polymerase chain reaction (PCR) method. Odds ratio (OR) with a 95% confidence interval (95% CI) was calculated using the chi(2) test. Results: The frequency of the 4R (4 repeats)/3R (3 repeats), 3R/3R genotypes, and 3R allele of PER2 VNTR in patients with PC was significantly higher than in the control group (p = 0003, p = 0.00004, respectively). PER2 VNTR 4/5 genotype was related to perineural invasion (p = 0.040). The genotype and allele distribution of PER3 VNTR variant did not show any statistical difference between the two groups (p > 0.05). PER2/PER3 VNTR 4/5-4R/3R combined genotype increased in the patient group (p = 0.013), while 4/5-4R/4R combined genotype was superior in the control group (p = 0.0001). Conclusions: Our work has indicated that PER2 VNTR 3R allele may play a crucial task in the pathogenesis of PC in Turkish patients, which may become a useful marker for predicting the development of PC. Furthermore, the PER2 VNTR genotype seems to be related to perineural invasion in PC. WOS:000606489600001 2-s2.0-85100932924 PubMed: 33393850

The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

Aim: In this study, we investigated the association between two miRNA variants and the risk of oral squamous cell carcinoma (OSCC), and explored the interaction between clinical factors in the Turkish population. Methods: In this case control study, a total of 142 subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism to analyze miR-146aG/C (rs2910164) and miR-149C/T (rs2292832) variants. Associations between OSCC risk and clinicopathological characteristics were analyzed by chi-square test Results: There was a significant difference in genotype and allele frequencies of miR-146aG/C variant between patients and control individuals. miR-146aG/C CC genotype and C allele were higher in the patient group compared to the control group (p=0.000, p=0.0001, respectively). Significant differences were also observed when the patients and the controls were compared according to CC vs GG+GC (p=0.0002) and GG vs GC+CC (p=0.002). In combined analysis, CC-CT combined genotype increased in patient group compared to controls (p=0.002), while GC-CT combined genotype increased in controls compared to patients (p=0.028), Conclusion: Our study provides evidence that miR-146aG/C variant may play an important role in susceptibility to OSCC in the Turkish population. Amaç: Bu çalışmada, iki miRNA varyantı ve oral skuamoz hücreli kanser (OSHK) riski arasındaki ilişkiyi inceledik ve Türk popülasyonundaki klinik faktörlerle arasındaki etkileşimi araştırdık. Yöntemler: Bu olgu-kontrol çalışmasında, miR-146aG/C (rs2910164) ve miR-149C/T (rs2292832) varyantlarını analiz etmek için toplam 142 kişi polimeraz zincir reaksiyonu- sınırlayıcı enzim parça uzunluk polimorfizmi ile genotiplendi. OSHK ve klinikopatolojik özelliklerin ilişkisi ?2 testi ile analiz edildi. Bulgular: Hastalar ve kontrol bireyleri arasında miR-146aG/C varyant genotip ve alel sıklıklarında önemli fark vardı. miR-146aG/C CC genotipi ve C aleli hasta grubunda kontrol grubuna göre daha yüksekti (p=0,000, p=0,0001, sırasıyla). Hastalar ve kontroller kıyaslandığında CC’ye göre GG+GC (p=0,0002) ve GG’ye göre GC+CC (p=0,002) önemli farklar saptandı. Kombine analizde, GC/CT kombine genotipi kontrollerde hastalara göre artmışken (p=0,0028), CC-CT kombine genotipi hasta grubunda kontrollere göre artmıştı (p=0,002). Sonuç: Çalışmamız miR-146aG/C varyantının Türk popülasyonunda OSHK’ye yatkınlıkta önemli rol oynayabileceği kanıtlarını göstermektedir. WOS:000568360300009 2-s2.0-85089165186

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.

Objective: The aim of the present study was to evaluate the prevalence of thyroid lesions detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) incidentally, determine malignancy risk and its relationship with maximal standardized uptake value (SUVmax) and FDG uptake pattern. Methods: Between February 2009 and February 2014, a total of 12713 patients underwent 18F-FDG PET/CT. Incidental thyroid uptake was seen in 710 patients and further diagnostic evaluation was performed on 147 patients with focal or diffuse FDG uptake. The 18F-FDG PET/CT findings of these patients and their association with malignancy were retrospectively reviewed. Results: The prevalence of thyroid incidentalomas detected by 18F-FDG PET/CT was 5.6% (710/12713). Of the 147 patients who underwent biopsy or thyroid surgery, histology was benign in 99 and malign in 48 patients. The malignancy risk of incidental thyroid lesions was calculated as 32.7% (48/147). The median SUVmax was 2.9 (0.6–27.4) in benign group, whereas 11.8 (2.4–72.9) in malign group and the difference between these groups was statistically significant (p

Hepatoselluler karsinom (HCC), hepatositlerden koken alan ve karacigerin en sik rastlanan primer malign tumorudur. Insidansi 20-200/100000 arasindadir. Ekstrahepatik metastazlar ileri evre intrahepatik tumoru olan hastalarda gorulur. HCC’larin %60’inda tani koyuldugunda ekstrahepatik metastaz mevcuttur. Literaturde HCC skalp metastazi oldukca nadir olup, %0.5-1.6 arasinda bildirilmistir. Olgumuz ekstrakranial metastaz ile prezente olan nadir bir metastatik HCC olgusudur.

Primerhiperparatiroidizm (PHP) parathormon seviyelerinin yüksekliği ile karakterizeendokrin bir hastalıktır. Hiperparatiroidizmkomplikasyonlarından biri olan Brown tümörü, osteoklastik aktivite sonucuortaya çıkar ve iskelet sisteminde lezyonlar, patolojik kırık ve ağrıya sebepolabilir. Brown tümörü hemhistopatolojik hem de radyolojik incelemelerde primer kemik tümörü,anevrizmal kemik kisti veya kemiğin dev hücreli tümörü ile karışabilir. Bu sunumdametastatik kemik tümöründen şüphelenilen ancak primer hiperparatroidi tanısıalan 50 yaşında bayan hastanın sunumu yapılmaktadır. Brown tümörleri benign karakterli lezyonlardır ama malignkemik hastalıklarını taklit edebilirler. Hastalığın ayırıcı tanısındaklinik, histopatolojik ve radyolojik bulguların birlikte değerlendirilmelidir., Primary hyperparathyroidism (PHP) is an endocrinedisorder characterized by the elevation of parathormone levels. Brown tumor,one of the complications of hyperparathyroidism, is the result of osteoclasticactivity resulting in lesions, pathological fractures and pain in the skeletalsystem. Brown tumor can be confused with primary bone tumor, aneurysmal bonecyst or giant cell tumor of bone in both histopathological and radiologicalexaminations. In this presentation, a 50-year-old female patient with asuspicion of metastatic bone tumor but diagnosed with primaryhyperparathyroidism is presented. Brown tumors are benign lesions, but they canmimic malign bone diseases. Clinical, histopathologic and radiological findingsshould be evaluated together in differential diagnosis of the disease.

Testicular metastasis of renal cell carcinoma (RCC) is a very rare condition in the literature. In this case report, a 56-year-old man with RCC in the right kidney and metastasis of RCC to the left testicle detected 12 months after nephrectomy was assessed and discussed in the context of literature information.

Although definitive chemoradiation (CRT) has been used for locally advanced laryngeal cancer for more than 2 decades, studies focusing on CRT failures in advanced laryngeal cancer are scarce. In this study, we aimed to determine the failure patterns and the survival outcomes in the patients who had recurrence after concurrent CRT for laryngeal cancer. Clinical records of the patients who had definitive concurrent CRT for laryngeal cancer between 2001 and 2014 at a tertiary referral center were reviewed. The end points of the study were 1-, 2-, and 3-year overall survival (OS) and disease-specific survival (DSS).In our results, there were 48 failures and the mean time period from the first diagnosis of disease to the diagnosis of recurrence was 18.0 months (range 2-72; standard deviation: 15.6). The most common recurrence pattern was local recurrence in 21 (47.9%) patients followed by regional recurrence in 11 (22.9%) patients. The 1 and 3 years OS rates were 41.7%, and 19.2% for the entire cohort, and 64.5%, and 29.7% for the patients who had not systemic recurrence at presentation of recurrence, respectively. The 1 and 3 years DSS rates were 43.5%, and 20.0% for the entire cohort, and 69.0%, and 31.8% for the patients who had not systemic recurrence at presentation of recurrence, respectively. All patients who had systemic recurrence initially (n = 13) died within 9 months (median = 4 months, range: 1-9 months). This study reveals that survival outcomes are unfavorable in the CRT failures and careful patient selection is critical to minimize failures. In the presence of systemic recurrence, disease course is aggressive.

Rapid and successful drug development has resulted in multiple treatment options for gastrointestinal cancer, requiring careful decision making for individual patients. The general theme in modern immunology is that the field is moving beyond establishing the fundamental principles of immune response mechanisms to applying these propositions to understand human diseases and develop new therapies. Immunotherapy has contributed enormously to cancer treatments with a virtual explosion in novel therapeutics including checkpoint inhibitors and other recently developed immunomodulators and the development of novel therapeutic approaches. Although the majority of gastrointestinal (GI) cancers are generally considered poorly immunogenic, clinical trials have revealed that some of the patients with various gastrointestinal cancers are highly responsive to immune checkpoint inhibition-based therapies. We paid special attention to the clinical relevance of immunology and emphasized how newly developed therapies work, including what their strengths and pitfalls are. This review aims to enhance the interest of practitioners in the many specialties and subspecialties that the discipline influences and to assist them in understanding this increasing complexity.

Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that plays a critical role in the repair of single-strand DNA damage via the base excision repair pathway. PARP inhibitors have substantial single-agent antitumor activity by inducing synthetic lethality. They have also emerged as promising anticancer targeted therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. PARP inhibition produces single-strand DNA breaks, which may be repaired by homologous recombination, a process partially dependent on BRCA1 and BRCA2. The PARP inhibitors olaparib, veliparib, talazoparib, niraparib, and rucaparib have predominantly been studied in patients with breast or ovarian cancers associated with deleterious germline mutations in BRCA1 and BRCA2. Ongoing clinical trials are evaluating the role of PARP inhibitors alone and in combination with other therapies, including selective inhibitors against key targets involved in the DNA damage response. In this review we summarize the use of PARP inhibitors in various tumor types, as well as possible approaches for overcoming resistance to PARP inhibitors.

WOS: 000378779800006, PubMed ID: 26975454, The aim of the present study was to evaluate the effect of crizotinib on visceral organs in an experimental rat model. Eighteen Wistar albino rats were divided into three groups: experimental toxicity was induced with crizotinib (10 mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally by gavage. Control group received only distilled water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively. Subjects in Group 1 and Group 2 had abnormal histology mainly in lung and liver. There were intraalveolar hemorrhage in lungs; mild portal inflammation, perivenular focal and confluent necrosis in liver; inflammatory reaction in renal pelvis and periureteral areas, and focal pancreatitis in pancreas. This study is the first to evaluate the histopathological features of toxicity of crizotinib in a rat model.

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

During last decades, laryngeal organ preservation strategies have emerged. The data about the oncological outcomes mainly come from multi-institutional prospective studies. In this study, we aimed to determine the oncological outcomes of different organ preservation regimens applied in routine practice. Patients who had definitive concurrent chemoradiation (CRT) for treatment of laryngeal cancer between January 2001 and June 2013 were retrospectively reviewed. There were 139 subjects who met the inclusion criteria. Three groups were defined: group A (n = 59) consisted of subjects who had concurrent cisplatin and radiotherapy (RT), group B (n = 47) consisted of subjects who had cisplatin/docetaxel-based concurrent CRT, and group C (n = 33) had induction chemotherapy before concurrent cisplatin and RT. The Kaplan-Meier estimated 5-year overall survival, disease-specific survival, disease-free survival, and local recurrence-free survival (LRFS) rates for the whole study group were 66.5, 69.2, 69.6, and 88.9 %, respectively. None of these survival rates were statistically different when the treatment arms were compared. The 3- and 5-year LRFS rates were significantly lower in subjects with a T4a tumor (p = 0.030). According to our results, the oncological outcomes of three different platinum-based concurrent chemotherapy schemes were similar and high local control rates could be achieved with the use of these protocols. Neoadjuvant chemotherapy before concurrent CRT was not superior to conventional concurrent treatment.

e13079 Background: Eribulin is an effective microtubule inhibitor for the treatment of ABC. Based on encouraging efficacy with docetaxel/cyclophosphamide, we hypothesized that eribulin combined with cyclophosphamide (EC) would be effective with tolerable toxicity. The aim of the study was to determine the maximum tolerated dose (MTD) of EC, followed by a dose expansion study to estimate the clinical benefit rate (CBR) of EC in pts with ABC. Methods: Study eligibility included pts with histologically confirmed ABC with any number of prior lines of therapy. Pts were treated using a dose escalation strategy with cohort expansion once MTD was determined. Dose level 0 (DL0): E 1.1 mg/m2 on days 1 and 8, C 600 mg/m2 on day 1 of a 21-day cycle. DL1: E 1.4 mg/m2 on days 1 and 8, C 600 mg/m2 on day 1 of a 21-day cycle. Phase II expanded enrollment at DL1. The primary objective of the phase II study was CBR [(complete response (CR), partial response (PR), and stable disease (SD)]. Secondary objectives were response rate (RR), duration of response (DOR), time to progression (TTP), and safety. Using a 2-stage design, responses in 3 of the first 22 pts allowed continued enrollment to a planned 40. Results: No dose limiting toxicities (DLT) were identified in phase Ib (n = 6). 3 pts were treated at DL0 and 3 at DL1, the MTD. 44 pts with ABC were enrolled at the MTD and are included in the analysis. 31 pts had HR+/HER2- disease, 12 pts had triple negative disease (TNBC), 1 pt had HR+/HER2+ disease. Median age was 56 yrs, prior treatment (rx) for ABC included a median of 1 line of hormone rx (range 0-6) and 2 lines of prior chemorx (range 0-7). CBR was 79.5% (35/44; 7 PR, 28 SD) and median PFS 16.4 wks (95%CI:13.8-21.1 wks). Longer PFS was observed in those with HR+ disease vs TNBC (18.1 vs 10.8 wks; P = 0.067). Adverse events (AE) of any grade included fatigue (68.2%, n = 30), neutropenia (ntp) (59.1%, n = 26), nausea (56.8%, n = 25), constipation (50%, n = 22), peripheral neuropathy (47.7%, n = 21), dyspnea (40.9%, n = 18), headache (36.4%, n = 16), and anorexia (36.4%, n = 16). The most common grade 3/4 AE ntp (47.7%, n = 21); 3 pts had febrile ntp. Dose reductions due to ntp were required to 500 mg/m2 C (n = 17) and to 1.1 mg/m2 in eribulin (n = 12). Conclusions: EC in heavily pretreated ABC resulted in an encouraging CBR of 79.5% and PFS of 16.4 wks, comparing favorably to single agent E (PFS 14.8 wks). Dose reduction and delays were due primarily to ntp. EC is an effective combination therapy with manageable toxicity in ABC. Clinical trial information: NCT01554371 .

1068 Background: A major limitation of endocrine therapy in hormone receptor positive (HR+) ABC is the development of resistance. Preclinical data suggests that higher levels of vascular endothelial growth factor (VEGF) are associated with endocrine therapy resistance. We conducted a phase II trial to evaluate the clinical benefit (CB) of PZ, a VEGF receptor tyrosine kinase inhibitor (TKI) combined with nonsteroidal aromatase inhibitors (NSAIs) in pts with ABC resistant to NSAIs. Methods: Eligibility included postmenopausal women with HR+ ABC and progressive disease (PD) after at least one month of NSAIs. Treatment was PZ 800 mg/day plus either letrozole or anastrozole. The primary endpoint was clinical benefit rate at 12 weeks (CBR12, wks). Secondary endpoints were PFS and safety. A CBR of 20% was considered a clinically meaningful comparison to the expected CBR of < 5% with continued NSAIs after PD. Using a 2-stage design, stable disease in at least 1 of the first 13 pts allowed continued enrollment to a planned 28. Results: 32 pts were enrolled; 28 are evaluable for study endpoints and all patients completed the study. The median age was 58 years (range: 41-77). Pts were heavily pre-treated, with a median of 2 prior hormone therapies (range 1-6) and 1 prior chemotherapy (range 0-8). 8 pts (28.6%) stopped treatment due to adverse events (AE) including hypertension (HTN), fever, transaminitis, nausea, vomiting, rash, hand foot syndrome and pulmonary embolism (PE); 6 pts progressed before wk 12. CBR12 was 46.4% (12 SD, 1 PR); CBR24 was 25% (5 SD, 2 PR). Median PFS was 20 wks (95% CI 11-48, and median PFS for pts with CBR12 was 24 wks. 7 pts had PFS > 6 months (24, 32, 36, 36, 48, 184 and 274 wks); 2 pts had PFS > 3 years (184 and 274 weeks). The most common grade 1/2 AE were nausea (48.2%), fatigue (33.3%), diarrhea (29.6%), back pain (22.2%), and arthralgias (22.2%). Grade 3/4 AEs included HTN (3/28; 11.1), transaminitis (3/28; 11.1%), headache (2/28; 7.4), heart failure, vertigo, nausea, oral pain, vomiting, fever, fatigue, and hypokalemia (one patient each: 3.7%). Conclusions: The addition of PZ to NSAIs resulted in a CBR12 of 46.4%, and a CBR24 of 25% in pts with heavily pre-treated ABC resistant to NSAIs. These results support clinical efficacy of antiangiogenic TKI in HR+ ABC, and suggest benefit in hormone resistant disease. Expected toxicities resulted in early discontinuation in 28.6%, which limited drug exposure. Clinical trial information: NCT 01466972 .

WOS: 000442916006728, …

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.

Angiogenesis plays a major role not only in the growth of the primary tumor, but also in metastasis. Due to the angiogenesis in granulation tissue, the tumor cells easily migrate to and locate in this region, thereby accelerating the pathological angiogenesis process and proliferation via presence of the angiogenesis-stimulating factors in this site. In this case report, we present tumor homing to granulation tissue following tooth extraction in a 68-year-old male patient with metastatic lung adenocarcinoma. He applied to hospital due to delayed wound healing after tooth extraction for tooth decay approximately 5 months after the diagnosis. A superficially swollen mass of 6 × 6 cm was detected in the tooth extraction site. The histopathological examination suggested that it was a lung carcinoma metastasis. The presence of tooth extraction history together with the pulmonary adenocarcinoma metastasis in the extraction site was explained as “tumoral homing” to granulation tissue following tooth extraction. This patient is of significance since it is the first case in the literature with “tumor homing” observed in the granulation tissue following tooth extraction.