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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.

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.

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.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is often associated with an aggressive phenotype and a poor prognosis. Cytotoxic chemotherapy remains the mainstay of treatment for most patients with metastatic TNBC (mTNBC), but duration of response is often short and median overall survival is only 12–18 months. Therefore, it is critical to identify novel treatment strategies to improve outcomes for these patients. In this review article, we discuss recent advances in treatment strategies for patients with mTNBC including the use of immune checkpoint inhibitors, targeted therapies, and antibody–drug conjugates. For each topic, we summarize important preclinical and clinical data, discuss implications for clinical practice, and highlight future research directions.

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.

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.

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

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 .

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.

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

Background: The development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of 4 mm) (p = 0.008), ulceration (p = 0.007), and pathologically N2 and N3 diseases (p = 0.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors. Conclusions: Our results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic ≥N2 disease were found to be significant predictors of BMs development. © 2013 Springer-Verlag Berlin Heidelberg.

Aim: Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the disadvantages of liver biopsy, many studies related to non-invasive biomarkers and scores have been performed. In this study, we aimed to assess the diagnostic value of serum direct markers and non-invasive fibrosis models to predict liver fibrosis in the treatment-naive chronic hepatitis B (CHB) patients and to compare their diagnostic performance. Methods: This study included 58 patients with a diagnosis of CHB virus infection and 30 healthy controls. Hyaluronic acid, tissue inhibitor of matrix metalloproteinase 1 and amino-terminal propeptide of type III procollagen were measured by enzyme-linked immunosorbent assay; and the Original European Liver Fibrosis panel, the Enhanced Liver Fibrosis (ELF) panel, PP score, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 indexes were calculated using the formulas taken from previous publications. Fibrosis stage was determined using Ishak's scoring system. Results: The fibrosis stages identified upon liver biopsy was F0 in 12 patients (20.7%), F1–2 in 36 (62.1%) and F3–5 in 10 (17.2%). The diagnostic value of all the non-invasive indices was low to detect mild fibrosis. We demonstrated that the diagnostic accuracy of HA is the best for predicting fibrosis of F3 or more (area under the receiver–operator curve, 0.902). In our study, the results from a combination of tests showed that ELF and APRI had the highest diagnostic value sensitivity of 90%, specificity of 100%, positive predictive value of 100% and negative predictive value of 96.4% for detection of fibrosis of F3 or more. Conclusion: In CHB patients, combination of ELF and APRI has a better diagnostic value in predicting fibrosis of F3 or more.

Tanidan l0 yil sonra gelisen lokal nuks ve uzak metastaz, renal hucreli kanserin (RCC) gec rekkurrensi olarak adlandirilir. Gec rekurrens %4.7-11 oraninda gorulmektedir. Bu olgu sunumunda RCC nedeniyle nefrektomi yapilan ve 16 yil sonra soliter beyin metastazi gelisen 54 yasindaki kadin hastayi tartismayi amacladik. Intrakranial tumor nedeni ile gross total eksizyon yapildi. Patolojik tanisi RCC metastazi olarak saptandi. Yapilan immunohistokimyasal incelemede beyin metastazi ile 16 yil once yapilan nefrektomi patolojisinin ayni oldugu saptandi. Postoperatif hastaya gamma-knife uygulandi. Hastaya interferon baslandi. Erken evre RCC hastalarinda da yillik kontrollerin >10 yil sonra da devam edilmesi ile nuksun erken saptanmasi ile cerrahi rezeksiyon sansi saglayabilir. Gelecekte yapilan calismalarla, gec rekkurens gelisiminde rol alan risk faktorlerinin belirlenmesi uzun takip suresi gereken hastalalari belirleme de katki saglayacaktir.

e15551Background: In this study, we aimed to investigate the efficiency and safety of initiation of regorafenib at different doses in mCRC Methods: Between January 2013 and January 2018, this study...

The presence of distant metastases (DMs) after the initial treatment of head and neck squamous cell carcinoma is associated with a poor outcome. The incidence of DMs in head and neck cancer is about 4-26%. The purpose of this study was to evaluate the prevalence of distant metastases and the factors predicting the development of DMs.Between January 2000 and December 2010, 292 patients with head and neck squamous cell carcinoma were included in this study.Thirty three patients (11.3%) developed local recurrences, 27 patients (9.2%) developed DMs. The median post DMs survival was 23.4 months (range 1.8-229.1). The factors that significantly increased the risk of DMs were the presence of local recurrence (p=0.0001, OR:17.32, 95% CI:4.86-19.90), pathologically positive neck (p=0.008, OR:5.97, 95% CI: 3.25-10.45), and primary tumor localized in oral cavity or lip (p=0.035, OR:2.6, 95% CI:1.43-4.65).Patients with these factors should be considered candidates for adjuvant systemic treatment and evaluated for early detection of DMs during follow-up.

The purpose of this study was to evaluate the clinicopathological features of patients with grade III glial tumors associated with recurrence after treatment.A retrospective analysis was carried out on 67 patients with grade III glial tumors between May 2007 and June 2013. Data were retrieved from patient electronic medical records and paper charts.The patient median age was 43 years (range 19-707 rpar;. Of these, 50.7% (N=34) had anaplastic astrocytoma, 29.9% (N=20) anaplastic oligoastrocytoma and 19.4% (N=13) anaplastic oligodendroglioma. Among these 67 patients, 41 (61.2%) developed local recurrence. Fifty seven of them (80.6%) received radiotherapy (RT) with concomitant temozolomide. Of these patients, 14 (20.9%) received RT with concomitant temozolomide alone, and 43 (64.2%) were treated with concomitant chemoradiotherapy followed by adjuvant temozolomide. Time to recurrence (TTR) of patients who received adjuvant temozolomide after concomitant chemoradiation (TTR=14 months, 95% CI 9.3-22.77 rpar; as initial treatment for grade III glial tumors was not superior to RT with concomitant temozolomide alone (TTR=21 months, 95% CI 14.8-35.2; p=0.224) In multivariate analysis, histologic subtype (p=0.015), age (p=0.019) and presence of neurologic symptoms (p=0.021) were independent predictive factors of recurrence.This analysis demonstrated that histologic subtype, age and presence of neurologic symptoms were significantly associated with recurrence in patients with grade III glial tumors. Adjuvant temozolomide was not significantly associated with recurrence in patients with grade III glial tumors. The identification of these predictors may be important for the patient follow-up and better treatment modifications.

The objective of this retrospective study is to investigate the association between survival and maximum standardized uptake values (SUVmax) of liver metastases detected by pre-treatment positron emission tomography-computed tomography (PET-CT) in patients with adenocarcinoma of unknown primary origin (ACUP). A total of 58 patients with ACUP and liver metastases confirmed histopathologically by liver biopsy and pre-treatment PET-CT were included in this study. SUVmax values of the liver lesions were measured and their association with survival was investigated. The median age was 62 years; 63.8 % of the patients were males and 36.2 % were females. The median overall survival was calculated as 10.7 months (OS). The median SUVmax of the liver metastases was 8.6. Accordingly, two groups were established: one with values

In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis.Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34).Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02].Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.

25 Background: Determination of HER2 status in advanced gastric cancer (GC) is important in clinical decision making. In the ToGA trial, trastuzumab based therapy demonstrated a significant OS benefit in patients with HER2 positive advanced GC. HER2 discordance in GC primary and its metastases has been long debated. The aim of the study was to evaluate the rate of HER2 discordance and its effect on treatment decisions in advanced GC. Methods: A total of 74 patients with advanced GC were included in the study. Both immunohistochemical staining (IHC) and dual-color silver in situ hybridization (SISH) were performed in all patients to evaluate the HER2 status of the primary lesion and paired metastasis. Results: The assessment of HER2 status with the IHC staining method and SISH revealed a discordance rate of 9.5% and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a HER2 negative status in primary tumor (IHC=0, SISH=negative), the HER2 status was positive for liver metastasis (IHC=2+, SISH=positive). Trastuzumab was added to the chemotherapy regimen. Conclusions: In this study, we found a higher rate of HER2 discordance between primary gastric tumor and metastatic lesions compared to the rates reported in previous studies. Detection of a HER2 positive metastasis with a HER2 negative primary tumor suggests that investigation of HER2 is also required for the metastatic lesion and that trastuzumab could be administered in case of a positive result.

In the head and neck mucosa, neuroendocrine carcinomas of the oral cavity is rare. Herein, we present the first report of a small cell neuroendocrine carcinoma in a 54-year-old man on the right lateral posterior tongue. It is important to remember that although neuroendocrine small cell carcinomas (SCCs) are most commonly seen in the lung, they rarely may arise in the extrapulmonary sites, including salivary glands, as well. As there is not any standard therapeutic regimen already existing, it is important to be aware of and to know how to deal with such rare cases.

Objective The objective of this retrospective study is to investigate the association between survival and maximum standardized uptake values (SUVmax) of liver metastases detected by pre-treatment positron emission tomography-computed tomography (PET-CT) in patients with adenocarcinoma of unknown primary origin (ACUP).

638 Background: In the present study, we investigate that which treatment choice is more effective in the human epidermal growth factor receptor 2 (HER2) positive breast cancer patients with brain metastases. Methods: Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 111 patients treated with lapatinib or trastuzumab after brain metastases eligible for the analyses were identified. Patients received both drugs consecutively or sequentially were excluded from the study. Results: Median age was 44 years (27-76) and 46 of the 111 patients (41.5%) had received lapatinib. Median time to development of brain metastases was 12.2 months (0-71). Sixteen patients (14.4%) had undergone surgery, 33 (29.7%) radiosurgery, and 108 (97.2%) whole brain radiation therapy (WBRT). Median overall survival (OS) after brain metastases was 15 months(95% confidence interval (CI): 12.3-17.6). Lapatinib usage was prolonged OS over trastuzumab alone (19.1 months vs 12 months, p=0.039).Other parameters affecting the survival were Karnofsky performance score (KPS, >70), number of brain metastases (>3), extracranial metastases (≥2), performed neurosurgery, and received radiosurgery. After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival [Odds ratio (OR), 0.57; p=0.02). Conclusions: Although this retrospective multi-center study had several limitations, study results suggest that the usage of lapatinib after brain metastases prolonged survival compared to the usage of trastuzumab. This result should be support with prospective studies.