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Introduction The efficacy of immune checkpoint inhibitors (ICIs) against malignant melanoma and numerously solid tumors has been demonstrated in several clinical studies. The incidence of immune-related adverse effects (irAEs) has increased after the rapidly expanding indications and clinical applications of ICIs. We present a case of nivolumab and ipilimumab-induced encephalitis with rapidly worsening consciousness and full recovery following ICIs suspension and high-dose steroid coupled with intravenous immunoglobulin (IVIG). Case Report A 67-year-old woman was diagnosed with stage 4 BRAF wild malignant melanoma with metastasis to the axillary and mediastinal lymph nodes. Beyond progression with dacarbazine, ipilimumab and nivolumab combination were administered at the second-line treatment of metastatic setting. A week after the first cycle patient was reported to have a fever of more than 38°C. Subacute cognitive impairment including mild changes in behavior was reported on the third day of fever. She suddenly developed confusion, dysarthria, and motor dysfunction a few days later. Due to the altered mental status accompanied by fever, lumbar puncture was performed with a pre-diagnosis of encephalitis, meningitis, and leptomeningeal carcinomatosis. Management & Outcome After excluding viral and autoimmune encephalitis, high-dose methylprednisolone was administered in addition to IVIG for 5 days with the diagnosis of immunotherapy-related encephalitis according to the recommendations for the management of irAEs. On the second day of the treatment patient's neurological status improved gradually. Discussion Being aware of symptoms of serious neurological irAEs associated with ICIs can prevent complications and improve survival.

Introduction: The objective of this study was to evaluate the clinical and laboratory outcomes of solid cancer patients who were reinfected with COVID-19. Methods: Patients who were tested negative on the Coronavirus disease 2019 (COVID-19) PCR test and those with improved clinical conditions after infection with COVID-19 were enrolled in this study. Patients who received a positive COVID-19 PCR test 28 days after the initial positive PCR test were considered as reinfected. Results: A total of 1024 patients with the diagnosis of solid malignancy and COVID-19 PCR positivity were examined. The reinfection rate was 3.1%. Mortality rate of reinfection was 34.3%. The serum ferritin and creatinine values in reinfection were found to be significantly higher than the first infection (respectively; p = 0.015, p = 0.014). Conclusion: This study has demonstrated one of the first preliminary clinical results of COVID-19 reinfection in solid cancer patients., Lay abstract Solid cancer patients are at a higher risk than general population in terms of Coronavirus disease 2019 (COVID-19) infectivity and COVID-19-associated death and disease. It is also known that COVID-19 infection has a more severe course in immunocompromised patients. Solid cancer patients may be a vulnerable subgroup of patients to reinfection with COVID-19. The rate of reinfection was 3.1% (n = 32) in our study population of 1024 solid cancer patients who were tested positive on a COVID-19 PCR test. The death rate of the patients with solid cancer was 34.3% (n = 11). In addition, we demonstrated that intensive care follow-up is significantly longer during the reinfection period. It was demonstrated that the time between the last dose of chemotherapy for the patients and the reinfection COVID PCR positivity did not affect the death rate. The COVID-19 pandemic has affected people's daily lives and treatments in many aspects. Owing to the high death rate of reinfection, even if cancer patients have reinfection, our approach is to continue cancer treatment as soon as the patient is cured. Finally, we support the priority vaccination of cancer patients.

Introduction To evaluate biosimilar understanding and preference trends of medical oncologists in Turkey. Methods A survey consisting of 24 multiple-choice questions with checkbox answers was conducted among medical oncologists. The questionnaire was divided into five parts to some intentions: demographic characteristics, general knowledge about biosimilars, knowledge about local approval and reimbursement issues, individual preference trends, and ranking the knowledge of their own. All answers were analyzed as whole cohort, specialists and fellows. Results Fellows (n = 47) consisted 42%, and academic clinicians (n = 37) consisted 35% of the participants. In the whole cohort, the overall rate of correct answers was 55.1% in the general knowledge about the biosimilars part, and 26.7% in the local approval and reimbursement issues part. At all, 57.7% of the participants declared that they object to switch from a reference product to a biosimilar product. The rate of those who defined themselves as extremely knowledgeable decreased from 8.1% to 2.7% in the whole cohort at the end of the survey. Conclusion The need for more accurate and clarified local regulations and education emerging in the biotechnology era must be met.

Background: The aim of this study was to determine the cause of death in patients who died within 30 days after the first dose of immunotherapy. Methods: The data of 1432 patients treated with immunotherapy in six tertiary referral hospitals were retrospectively analyzed. Results: It was determined that 34 (2%) of the patients died within 30 days after the first dose of immunotherapy. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second- or subsequent-line of therapy. The most common cause of death was disease progression and thromboembolic events. Conclusion: Preliminary results of the current study might give some clues to define the patient population in whom the fatal side effects of immunotherapy might be encountered.

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: COVID-19 reinfection has been increasingly reported. Immunocompromised patients may be more susceptible to COVID-19 reinfection due to impaired immune responses to the virus. The current study aimed to evaluate the clinical and laboratory outcomes of solid cancer patients who were reinfected with COVID-19. Methods: Patients with a diagnosis of solid cancer and COVID-19 PCR positive were screened. The patients enrolled whether patient has at least one negative COVID-19 PCR test and clinical improvement. In addition to that at least 28 days after the previous positive COVID-19 PCR result, the patient must have a confirmed COVID-19 PCR positive result again. Results: Total 1024 patients with COVID-19 PCR positive solid malignancy were screened. Thirty-two patients were included in the study. The median time between the first COVID-19 infection and reinfection was 46 (30-194) days. The reinfection rate was 3.1%. The most common cancer subtype was lung cancer. Mortality rate of reinfection was 34.3% (n=11). Ferritin and creatinine values of serum parameters in reinfection were found to be significantly higher compared to the first infection, respectively (p:0.015, p:0.014). Nine patients with only 1 comorbidity had higher mortality (p=0.052). During reinfection period rate of patients hospitalized in intensive care unit was significantly higher compared with rate of patients during first COVID-19 infection (p:0.002). The mortality rate in 8 patients using antiaggregant or anticoagulant for a long time was not statistically different from the group who did not use it (p:0.681). Conclusions: Solid cancer patients have a higher mortality rate in COVID-19 reinfection. The reinfection rate was 3.1%. This study demonstrated one of the first preliminary clinical results of COVID-19 reinfection in solid cancer patients. Legal entity responsible for the study: Oktay Unsal. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

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

Ewing's family of tumors is aggressive tumors and frequently arises from bone and soft tissue. They might also arise from nonosseous structures such as gastrointestinal tract, adrenal glands, or kidney. Primary renal Ewing's sarcoma (ES)/primitive neuroectodermal tumor is an extremely rare entity which has aggressive clinical course. These high-grade malignant tumors predominantly affect adolescents and young adults. Patients mostly present with nonspecific symptoms such as pain, hematuria, mass, and sensitivity. It is confused with renal cell cancer in imaging techniques. The definitive diagnosis is based on the histopathological examination. Surgical or radiotherapy treatment is used for local control and multiagent chemotherapy used for systemic treatment. Despite all treatment options, prognosis is poor. We aimed to describe the diagnosis and follow-up and treatment of renal ES case that was considered as renal cell carcinoma in imaging but diagnosed as ES via histopathology.

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.

Purpose: Helicobacter pylori(HP) is a significant causative agent of gastric cancer (GC). However, the underlying mechanisms involved in its pathogenesis and association with oncoproteins are unclear. The aim of the present study was to evaluate the relationship between HP infection and human epidermal growth factor receptor 2 (HER2) expression in GC patients. Materials and Methods: Surgery (173) or endoscopic biopsy (35) specimen of 208 patients diagnosed with GC was evaluated for the presence of HER2 and HP. HER2 expression was assessed by fluorescence in situ hybridization (FISH) method, whereas HP status was evaluated histologically. Giemsa stain was used to identify HP status, in case HP could not be recognized in routine H and E-stained sections despite careful examination Results: The median age was 63 years (27–91), and most patients were male (male/female: 149/59). Of all the 208 patients, HP was positive in 87 (41.8%) and negative in 121 (58.2%) patients. FISH positivity for HER2 was observed in 41 (19.7%) patients, whereas FISH negativity was observed in 167 (80.3%) patients. According to the Chi-square test, patient distribution was 21 in HER2-positive HP-negative group, 20 in HER2-positive HP-positive group, 100 in HER2-negative HP-negative group, and 67 in HER2-negative HP-positive group. No correlation was found between HP and HER2 status (P = 0.314). HP positivity had significant effect on median overall survival (27.4 vs. 12.9 months, P = 0.046). Conclusions: Our results suggest that there is no relationship between HP infection and HER2 status in patients with GC.

e20532Background: Prognostic significance of PD-1/PD-L1 axis expression in non-small cell lung cancer (NSCLC) remains uncertain despite being a predictive biomarker for novel immunotherapeutics. In...

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.

42nd European-Society-for-Medical-Oncology Congress (ESMO) -- SEP 08-12, 2017 -- Madrid, SPAIN, WOS: 000411324001166, …, European Soc Med Oncol

Introduction We investigated the impact of modern chemotherapy regimens and bevacizumab following pulmonary metastasectomy (PM) from metastatic colorectal cancer (CRC). Methods A total of 122 consecutive patients who were curatively resected for pulmonary metastases of CRC in twelve oncology centers were retrospectively analysed between January 2000 and April 2012. Results Of 122 patients, 14 did not receive any treatment following PM. The remaining 108 patients received fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) chemotherapy combinations. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). Median recurrence-free survival (RFS) was 17 months and median overall survival (OS) has not been reached at a median follow-up of 25 months after PM. Three and five-year OS rates were 66% and 53%, respectively. RFS and OS were similar, irrespective of the chemotherapy regimen or BEV use. Positive pulmonary margin, KRAS mutation status, and previous liver metastasectomy were negative independent prognostic factors for RFS, while pathologically confirmed thoracic lymph node involvement was the only negative independent prognostic for OS in multivariate analysis. Conclusions No significant RFS or OS difference was observed in respect to chemotherapy regimens with or without BEV in patients with pulmonary metastases of CRC following curative resection.

Cancer patients who start receiving chemotherapy have difficulty in understanding the state of their disease, the prognosis, and the purpose of treatment. We used a survey to evaluate the extent of perception of chemotherapy goal among cancer patients. Two hundred sixteen cancer patients who received chemotherapy for the first time participated in the study. The presence of depression and anxiety was assessed using the “Hospital Anxiety and Depression Scale” (HAD). The consistency between the patients’ perception of the chemotherapy goal and the physician’s perception was described as “right,” and the inconsistency was described as “wrong.” Among the patients who participated in the survey, 53.2 % (n = 115) were receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative treatment for metastatic disease. The rate of right and wrong perception of the chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the rate of confused patients was 18.9 % (n = 41). The level of education was shown to be the only parameter involved in accurate perception of the treatment purpose (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219–0.903). In this study, there was a 51.9 % consistency between the physician’s perception and that of the patient regarding the purpose of treatment. We demonstrated that the level of education was the unique factor in accurate perception of chemotherapy goal among cancer patients.

Trastuzumab is known to be effective for early and advanced stages of breast cancer but optimal duration for early-stage breast cancer (EBC) is not well known. We evaluated the efficacy and toxicity of 9- and 52-week trastuzumab therapy for EBC retrospectively.In this multicenter study, the medical records of all patients with EBC were analyzed in 8 centers retrospectively. Totally consecutive, 479 female patients who received trastuzumab in the adjuvant treatment were evaluated for disease-free survival (DFS), overall survival (OS), efficacy, and toxicity.There were 181 (37.8 %) and 298 (62.2 %) patients in the 9- and 52-week trastuzumab groups, respectively. Median follow-up was 30.6 months (5.7-68.9) in the 9-week trastuzumab group and 29.3 months (5.9-59.6) in the 52-week trastuzumab group. Thirty-six month DFS was 90 and 85 % (P = 0.132) in the 9- and 52-week trastuzumab treatment groups, respectively, and 36-month OS was 96 and 97 % in the 9- and 52-week trastuzumab groups, respectively (P = 0.779). Symptomatic cardiotoxicity was observed in 1 (0.6 %) patient in the 9-week trastuzumab group and in 4 (1.3 %) patients in the 52-week trastuzumab group.In this study, similar outcomes were found in the 9- and 52-week trastuzumab treatment groups.

Background The current study is the first to evaluate the biochemical and histopathological features of hepatic toxicity of lapatinib. Methods Twenty Wistar albino rats were allocated into three groups: experimental toxicity was induced with lapatinib (10 mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally in a single dose by gavage. Control group received only sterile 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. Results Subjects in Group 1 and Group 2 had significantly higher levels of alanin aminotransferase (ALT), albumin, triglyceride and very low density lipoprotein (VLDL) when compared with the control group. None of the subjects in the two experimental groups showed normal histology. There were parenchymal acinar transformation zones, sinusoidal dilatation, hydropic degeneration of hepatocytes, vacuolisation of hepatocytes around the portal areas, and mild inflammation with dominance of mononuclear cells besides neutrophil and eosinophil leucocytes in portal areas, especially pronounced in Group 2. Conclusion This study demonstrated that lapatinib brings about deterioration of lipid profile and triggers hepatic toxicity mainly as sinusoidal injury with elevation in transaminase levels, especially ALT.

Bevacizumab-based chemotherapy has become the standard of care in metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define prognostic significance of these parameters in response to bevacizumab in these patients.The levels of these parameters in serum samples were quantified by a commercially available ELISA kit in 31 MCRC patients before and after 2 cycles of therapy and 25 healthy controls.Pretreatment sFAS levels in MCRC patients was significantly lower than the levels of controls (p = 0.043). There was no significant difference in sFAS and sFASL levels in MCRC patients before and after bevacizumab-based treatment. There was no significant difference in sFAS/sFASL ratio in MCRC patients before and after treatment and controls. Soluble DR5 levels were significantly higher in pretreatment serum samples compared with controls (p = 0.008). However, pretreatment sTRAIL and sDR4 levels were similar to the levels of controls. There was no significant difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after treatment. When patients were grouped according to treatment response (responders vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in responding patients compared with non-responders (p = 0.029). Significant correlations were observed between post-treatment sFASL and sDR4, sFAS and sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5.Non-significant changes in apoptotic markers with bevacizumab-based chemotherapy showed that they have no prognostic significance in MCRC patients. Significant change in sFAS/sFASL ratio according to treatment response could be an indicator of chemosensitivity.

The aim of the study was to evaluate the efficacy and tolerability of gemcitabine and uracil-tegafur (LIFT) combination in patients with advanced pancreatic carcinoma, retrospectively. Thirty-one patients, including 27 with metastatic disease, were treated with gemcitabine at a dose of 1000 Mg/m(2) in 30 minutes on days 1 and 8, and oral UFT 300 mg/m(2) on days 1-14, as the first-line regimen in advanced stage. The cycle was repeated every 21 days. A total of 116 cycles of chemotherapy were administered, with a median of 3 cycles per patient (range 1-13). The objective response rate was observed in 6 (19.3%) patients with 1 (3.2%) complete response, and 5 (16.1%) partial responses. The median response duration was 4 (range, 3-14) months. Eight (25.8%) patients had a standard deviation of more than 3 months. Median overall survival was 8 months (95% Cl, 6-10 months) and median time to progression was 4.2 months (95% Cl, 1-6 months). This combination was generally well tolerated. There were no life-threatening side effects. Most common toxicities were of hematologic and gastrointestinal nature. In conclusion, this regimen was well tolerated and seemed to have a moderate activity in the palliative treatment of advanced pancreatic carcinoma.

Aims To evaluate preoperative concomitant chemoradiation using cisplatin plus docetaxel followed by consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC). Patients and methods Medical records of patients with locally advanced unresectable NSCLC (stage IIIA and IIIB) treated with concomitant chemoradiotherapy using cisplatin + docetaxel combination followed by consolidation chemotherapy were retrospectively evaluated. All the patients were consecutively treated. Chemotherapy consisted of weekly cisplatin 20 mg/m(2) and docetaxel 20 mg/m 2 during radiotherapy. Radiotherapy dose was 58-66 Gy given in 2 Gy fractions, 5 days per week. The patients were subsequently referred to surgery if adequately downstaged. Consolidation chemotherapy using cisplatin and docetaxel both at doses 75 mg/m2 every 3 weeks followed local therapy in all patients. Results A total of 54 patients were evaluated (49 males, 5 females with a median age of 58 years; 41 [75.9%] stage IIIB and 13 [24.1%] IIIA). Twelve patients (22.2%) achieved pathologic complete response and 20 (37%) partial response. Downstaging was possible in 32 patients (59.3%). Twenty-six patients (48.1%) were operated after concomitant chemoradiotherapy (pneumonectomy [n = 2], lobectomy [n = 12], and wedge resection [n = 12]). Toxicity was tolerable. Median progression-free survival and overall survival (OS) for the entire cohort were 14 and 22 months, respectively. In resected patients (n = 26), median PFS and OS have not been reached with a median follow-up duration of 24 months. Conclusion Preoperative concomitant chemoradiation using weekly cisplatin and docetaxel followed by surgery and consolidation chemotherapy is effective and well tolerated in patients with unresectable locally advanced NSCLC.

The aim of the study was to evaluate the toxicity and efficacy of 62 patients with locally advanced nasopharyngeal carcinoma (NPC) (stage III, IVA, IVB) treated by three different modalities. Cisplatin was given weekly 35 mg/m(2)/day or every 3 weeks 100 mg/m(2)/day during radiotherapy (RT) in all patients. Patients were classified into following three groups: The patients in the group 1 (n = 23) were treated only with concurrent chemoradiotherapy (CCRT). In the group 2 (n = 15), before the CCRT, neoadjuvant chemotherapy, consisting of intravenous cisplatin and docetaxel on day 1, every 3 weeks treatment cycles was administered. In the group 3 (n = 24), adjuvant chemotherapy, consisting of cisplatin on day 1 and 5-flourouracil on day 1 to 5 every 3 weeks was used after CCRT. Three arms were treated with the same RT technique and dose. There was no difference for age, sex, and stage among the groups. Radiotherapy was administered in planned dose for all patients. A total of 82% patients completed planned chemotherapy concurrent with RT. The treatment related adverse effects were mild or moderate in intensity. There was no statistical difference between the groups regarding the treatment responses. Complete response rate of RT was 73.9%, 86.7%, and 87.5%, respectively. Median progression free survival (PFS) and overall survival (OS) were 13, 12, 9 months and 22, 20, 15 months for groups 1, 2, 3, respectively. No difference was observed in median OS and PFS among three groups. In our study, the efficacy and toxicity of neoadjuvant and/or adjuvant chemotherapy with CCRT and CCRT alone were found similar.

Matrix metalloproteinases (MMPs) are frequently expressed in malignant tumors and play an important role in tumor invasion and metastasis. The aim of this study was to evaluate role of serum MMP-2 and MMP-7 levels in patients with ovarian cancer. Serum levels of MMP-2 and MMP-7 were measured in 28 patients with ovarian carcinoma, 2 with borderline ovarian tumors, 10 with non-malignant gynecological disease and 30 healthy women by Enzyme-Linked Immunosorbent Assay (ELISA). Serum MMP-7 level was significantly (10.24 +/- 1.35 ng/ml) higher in the patients with ovarian malign tumors than healthy controls (3.29 +/- 1.64 ng/ml) (P < 0.05). Postoperative levels of MMP-7 (7.68 +/- 1.17 ng/ml) were significantly lower in patients with malign ovarian tumors than those of preoperative level (10.24 +/- 1.35 ng/ml) (P < 0.05). Serum MMP-2 levels were significantly lower in the patients with ovarian malign tumors (227.51 +/- 9.91 ng/ml) than those in the healthy controls (279.12 +/- 73 ng/ml) (P < 0.05). There was no significant difference in serum levels of MMP-2 and MMP-7 in patients with benign ovarian disease when compared to healthy controls and patients with malignant disease (P > 0.05). As a conclusion, MMP-7 can be a useful serum marker to show disease activity in malignant ovarian tumors.

To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients.Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression.Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive.Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.

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.

Objective Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer. Methods A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis. Results The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization 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 human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen. Conclusions In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.

Treatment of non-Hodgkin's lymphoma with the CHOP regimen consists of intravenous cyclophosphamide 750 mg/m(2) (day 1), intravenous doxorubicin 50 mg/m(2) (day 1), intravenous vincristine 1.4 mg/m(2) (day 1), and oral prednisone 100 mg (days 1-5). This regimen is administered in cycles of approximately 3 weeks; a total course of treatment consists of six cycles. We report the case of a 23-year-old woman with diffuse large-cell lymphoma who received an accidental overdose of this chemotherapeutic regimen. The first cycle of her CHOP regimen was initiated (day 1) in our outpatient unit; she was then discharged home. Unfortunately, the patient went to another hospital located in the small city where she lived, and all remaining doses of the total course of treatment were administered over the next 5 consecutive days, with no interruption in therapy. She had received cumulative doses of cyclophosphamide 6000 mg, doxorubicin 420 mg, and vincristine 12 mg. She was transferred to our hospital after she developed pancytopenia, fever, and ileus. With the help of intensive supportive care and symptomatic treatment, the patient recovered and was discharged home after a hospital stay of 25 days. After 56 months, she was free of disease and treatment-related toxicities. Only experienced clinicians should administer chemotherapy, and thorough records must be kept to document the chemotherapy administered, dosages, dates of administration, the procedure used, and the schedule of cycles administered.

Interdigitating dendritic cell tumor (IDCT) is an extremely rare malignancy. It occurs primarily in lymph nodes, but extranodal involvement has also been reported. A 38-year-old woman with IDCT with breast and cervical lymph-node involvement is reported in this paper. To our knowledge, this is the first case of IDCT originating from the breast. In the breast and lymph node, the tumor displayed diffuse sheets, fascicles and storiform growth pattern. It was composed of oval to spindle cells with pale to eosinophilic cytoplasm, ill-defined cell outlines, oval nuclei with vesicular chromatin and prominent eosinophilic nucleoli. Mitotic activity was three per ten high-power fields. The neoplastic cells were intermingled with small mature lymphocytes and plasma cells. Immunohistochemical studies showed that the tumor cells were strongly and diffusely positive for vimentin, CD68, S-100 protein, CD45/leukocyte common antigen and fascin and focally positive for lysozyme, alpha-1 antitrypsin and CD4. Ki-67 labeling index was 10%. The patient was treated with combined therapeutic approaches, including surgery, radiotherapy and chemotherapy. IDCT has the potential for an aggressive clinical course. However, 32 months after the initial diagnosis, the patient is still alive and being followed with a stable tumor burden.

Background and aims. The impact of a stoma on a patient's life is little discussed and is often underestimated, as well as the contribution of stomatherapy to health-related quality of life (QOL). This present study examined the problems faced by patients with ileostomies or colostomies and the possible contribution of stomatherapy to QOL. Patients and methods. Forty-three selected and well-documented stoma patients who had properly constructed, well functioning end colostomies or ileostomies were analyzed. Further analyses were carried out for the subgroups of patients with irrigating colostomies (n=16), nonirrigating colostomies (n=15), and ileostomies (n=12). The digestive disease QOL questionnaire 15 (DDQ-15) was used to analyze QOL before and 3 months after stomatherapy. A second questionnaire consisting of 11 questions with yes/no answers was also used before and 3 months after stomatherapy to define more specifically the stoma-related problems of each patient as well as the frequency of each issue in a patient group at a given time. Results. Cumulatively the mean QOL score was significantly higher after stomatherapy than before. Before stomatherapy the irrigating colostomy patients had the highest QOL score and the ileostomy group the lowest. QOL scores 3 months after stomatherapy were significantly higher in all groups than before. Again, the irrigating colostomy patients had a significantly higher score than the nonirrigating colostomy and ileostomy patients. Cumulatively all of the items improved significantly after stomatherapy, such as getting dressed, bathing, and participating in sports. Conclusion. These findings confirm that colostomy or ileostomy has a profoundly negative impact on QOL. Specialized counseling of these patients by a dedicated team improves QOL significantly.

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.

In this study, we investigated the rate of human epidermal growth factor receptor 2 (HER2) overexpression in gastric (GC) and gastroesophageal junction cancers (GEJCs) and the relationship with HER2 expression and clinical, pathological parameters and prognosis. Surgery or biopsy specimen of 598 (436 males, 162 females) patients with GC or GEJC was evaluated for the presence of HER2 overexpression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. HER2 IHC scores were as follows: 418 (69.9 %) IHC 0, 58 (9.7 %) IHC 1+, 50 (8.4 %) IHC 2+, 72 (12 %) IHC 3+. Among 50 patients with IHC 2+, 18 (38.2 %) were FISH positive, and 29 (61.7 %) were FISH negative for HER2 amplification. Patients were regarded as HER2 positive in case of IHC 3+ disease or IHC 2+ disease with a positive FISH test result for HER2 amplification. In the primary analysis population, 90 (15 %) were considered HER2 positive. HER2 positivity was higher in intestinal GC compared to diffuse GC (16.9 vs 6.6 %, p = 0.014). HER2 positivity was significantly higher in well and moderately differentiated tumors than poorly differentiated tumors (p

Primary tubal carcinoma is a very rare gynaecological malignancy with an incidence of 2.9–5.7/1,000,000 (Riska and Leminen 2009; Stewart et al. 2007). Patients with this disease generally present w...

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

Summary We describe a rare case with metastatic involvement of the gastrointestinal tract (colonic metastasis) secondary to lung cancer. After diagnostic work-up, a left hemicolectomy was performed. Patient has been alive and healthy 9 months after operation. We report the first case with the longest survival period after the diagnosis of metastasis, although the symptomatic gastrointestinal metastases from lung cancer generally follow a poor prognosis because of their advanced state and multiplicity.

Background: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. Methods: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. Results: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. Conclusion: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.

Summary Background Four cycles of AC have been accepted as the standard chemotherapy in breast cancer. In the present randomized study we aimed to assess the efficacy of adjuvant etoposide + cisplatin (EP) combination following four cycles of standard adriamycin + cyclophosphamide (AC) in premenopausal patients with operable breast cancer and axillary lymph node metastasis. Patients and methods Premenopausal patients with positive axillary lymph nodes following curative modified radical mastectomy were randomized to either four cycles of AC (82 patients) or four cycles of AC + two cycles of EP (83 patients). Results Median follow-up is 72 months. All randomized and eligible patients are included in the analysis (AC: 80 patients, AC + EP: 78 patients). The five-year disease-free survival (DFS) for the AC + EP group was significantly better when compared to AC group (45.5% vs. 30.4%; P = 0.048). Again, the five-year overall survival (OS) of the whole group was in favor of AC + EP arm, though without statistical significance (68.6% vs. 59.1%; P = 0.247). Conclusion Two cycles of EP following four cycles of AC decreased the relapse rate in operable breast cancer patients.

e18535 Background: 18F-FDG-PET is a functional imaging method and widely used for initial diagnosis, staging and response evaluation in the treatment of malignant lymphomas. We evaluated the FDG-PE...

Background. Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. Patients and Methods: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). Results: Three patients achieved a complete response (7.5%),5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). Conclusion: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.

The aim of this study was to evaluate the role of whole body 18F-FDG PET/CT imaging in the detection of primary tumors in patients with a metastatic cancer from an unknown primary site.The study population consisted of 43 patients with a biopsy proven metastatic disease, negative conventional diagnostic procedures (including CT/MRI/endoscopic procedures) and a whole body 18F-FDG PET/CT examination. Patients' records were retrospectively analyzed. According to the final pathologic diagnoses, rate of detection of the primary tumor site was determined. Additionally, overall patient survival was calculated to evaluate the prognostic value of 18F-FDG PET/CT findings.A primary tumor site was shown by 18F-FDG PET/CT in 24 patients (24/43; 55.8%). In 18 patients 18F-FDG PET/CT scans were negative (18/43; 41.8%). In a patient with an adenocarcinoma metastasis 18F-FDG PET/CT was falsely positive for an inflammatory lesion in the lung. Among the 18F-FDG PET/CT positive and negative groups median overall survival was not significantly different (log-rank p=0.573).Whole body 18F-FDG PET/CT imaging has a high rate of detection of a primary tumor in patients with a carcinoma of unknown origin.

Background Temozolomide is a novel cytotoxic agent for malignant gliomas. However, treatment failure occurs approximately in half of patients, and the optimal regimen in this setting has yet to be defined. In the present study, we assessed retrospectively the efficacy and toxicity of the combination of carboplatin and oral cyclophosphamide in temozolomide-resistant patients. Methods We evaluated the medical records of 30 patients with malignant gliomas. After failure of temozolomide therapy, patients were treated with a combination of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest, with the treatment repeated every 4 weeks. Results All patients were evaluated for response and toxicity. The objective response rate was 30%, including 9 partial responses. Median time to disease progression and median overall survival was 7 months and 8 months, respectively. Clinically responsive patients had statistically significant longer progression-free survival and overall survival than unresponsive patients. Hematological side effects were commonly observed toxicities, with neutropenia the most frequent. Conclusions Our data suggest that carboplatin and oral cyclophosphamide therapy is a convenient regimen after failure of temozolomide therapy in patients with malignant gliomas because of its activity, feasibility and tolerability. Further prospective studies are needed in this setting.

Background: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was administered concomitantly with radiotherapy, and thereafter as consolidation treatment. Patients and Methods: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m(2)/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m(2) on days 1-5 every 28 days for 6 cycles. Results: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities. Conclusion: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.

In this study, we investigated the activity of single agent gemcitabine in the second-line setting of non-small cell lung cancer (NSCLC). File records of 21 patients treated with single agent gemcitabine in advanced NSCLC who received one prior chemotherapy including a taxane and platinum combination were retrospectively evaluated. Treatment consisted of IV gemcitabine 1,250 mg/m(2) on days 1 and 8, followed by a 1-week rest repeated every 3 weeks. A partial response was achieved in four (19%) patients. The median response duration was 16 (range, 12-32) weeks. Six (29%) patients had a SD more than 3 months. The median time to progression was 16 (range, 8-32) weeks. No complete response was observed. Median overall survival was 36 weeks for second-line gemcitabine in all patients (95%: CI 5-13 months). Hematological toxicity (all grades) was reported by 9 (42.9%) patients. One (4.75%) patient experienced grade 3/4 neutropenia. Grade 3/4 nausea and vomiting and mucositis were reported in one (4.75%) patient. In conclusion, this study shows that single agent gemcitabine is active and well tolerated as a second-line therapy for advanced NSCLC.