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Hemophagocytic Lymphohistiocytosis (HLH) is a severe and potentially life-threatening condition characterized by an excessive and uncontrolled activation of the immune system. ICI-related hemophagocytic lymphohistiocytosis (irHLH) is a rare immune-related adverse event with an incidence of 0.03% to 0.4%. Although rare, it can be potentially lethal, with a high mortality rate of up to 50% in some cases. We present a patient with recurrent glioblastoma who developed Hemophagocytic Lymphohistiocytosis s a result of nivolumab treatment and was subsequently managed with cytokine-directed therapy (tocilizumab). Early diagnosis and treatment of Hemophagocytic Lymphohistiocytosis (HLH) associated with immune checkpoint inhibitors (ICIs) are indeed crucial due to the potentially life-threatening nature of the condition.Cytokine-based treatments (such as anti-IL-6) may be appropriate for patients who do not respond to high-dose steroids.

Purpose: To describe the long-term effects of an ASP among febrile neutropenia (FN) patients., Methods: A quasi-experimental study was conducted between 2015 and 2023 at a tertiary care hospital in Istanbul, Türkiye. The ASP was implemented for FN patients, and the effects were assessed before and after the ASP interventions, which included FN clinical pathways and regular multi-disciplinary meetings with relevant healthcare workers., Results: A total of 489 FN episodes of 290 patients were included, 42% were female, and the mean age was 56 years (SD: 15, range: 18-89 years). After the intervention, the rate of appropriate antimicrobial therapy at the levels of starting (p = 0.005), switching (p < 0.001), and de-escalation/discontinuation, (p < 0.001) significantly increased. Another positive impact of the ASP was a significant reduction in candidemia (from 4.88 to 0.74, p = 0.004), as well as a significant reduction in the 90-day mortality rate (from 19 to 5%, p < 0.001). In multivariate analysis, having a gram-negative bloodstream infection, prolonged days with fever, and a high risk for neutropenia were found to be significant predictors of 90-day mortality, while follow-up with ASP significantly reduced mortality., Conclusion: Implementation of ASP led to reduced candidemia and LOS without increasing mortality, even in a country with a high rate of antimicrobial resistance. Implementation of sustainable ASP for FN patients is critical in combating antimicrobial resistance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce., Objective: We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey., Patients and Methods: This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024., Results: The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months., Conclusions: In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings., Competing Interests: Declarations Funding The authors received no financial support for the research, authorship, and/or publication of this article. Conflict of interest statement Feride Yılmaz, Serkan Yaşar, Nil Molinas Mandel, Turgut Kaçan, Melek Özdemir, Gamze Gököz Doğu, Nilay Şengül, Nezih Meydan, Fatma Buğdaycı Başal, Pınar Kubilay Tolunay, Melda Berber Hamamcı, Oğuz Salih Dinçer, Aykut Bahçeci, Leyla Özer, Miraç Ajredini, Önder Kırca, Özlem Yersal, Orçun Can, Meral Günaldı, Gökhan Demir, and Şuayib Yalçın declare that they have no conflicts of interest that might be relevant to the contents of this article. Ethics declarations The study was conducted in accordance with the Declaration of Helsinki and its amendments and with Good Clinical Practice guidelines. Ethical approval (approval date and number 2 April 2024, 23/536) for this study was obtained from the Hacettepe University Health Sciences Research Ethics Board, Turkey. Consent to participate The need for consent for this study was waived by the institutional review board (Hacettepe University Health Sciences Research Ethics Board) because of its retrospective design. Consent to publish Not applicable. Availability of data and materials Since the participants in this retrospective study, which was conducted with the permission of the Hacettepe Health Sciences Ethics Committee, did not give written consent for their data to be disclosed to the public, supporting data are not available owing to the sensitive nature of the research. Code availability Not applicable. Author contributions Feride Yilmaz: conceptualization; data curation; formal analysis; investigation; methodology; validation; visualization; writing—original draft. Nil Molinas Mandel, Turgut Kaçan, Melek Özdemir, Gamze Gököz Doğu, Oğuz Salih Dinçer, Leyla Özer, Miraç Ajredini, Önder Kırca, Özlem Yersal: conceptualization; data curation; investigation; methodology; validation; visualization. Serkan Yaşar and Şuayib Yalçın: conceptualization; data curation; methodology; writing, review and editing. Nilay Şengül Samancı, Nezih Meydan, Fatma Buğdaycı Başal, Pınar Kubilay Tolunay, Melda Berber Hamamcı: conceptualization; data curation; methodology; supervision; writing, review and editing. Aykut Bahçeci, Orçun Can, Meral Günaldı, Gökhan Demir: conceptualization; methodology; supervision; validation; review and editing. Şuayib Yalçın: conceptualization; data curation; methodology; supervision; validation; review and editing., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes., Methods: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response., Results: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16)., Conclusion: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC)., Patients and Methods: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria., Results: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC., Conclusions: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer., Competing Interests: Conflicts of interest and sources of funding: B.E. is supported by the European Urological Scholarship Programme through a 1-year research scholarship., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience., Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed., Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity., Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial., Competing Interests: None

Colorectal cancer is the third most common cancer in Turkey. The current guidelines do not provide sufficient information to cover all aspects of the management of rectal cancer. Although treatment has been standardized in terms of the basic principles of neoadjuvant, surgical, and adjuvant therapy, uncertainties in the management of rectal cancer may lead to significant differences in clinical practice. In order to clarify these uncertainties, a consensus program was constructed with the participation of the physicians from the Acıbadem Mehmet Ali Aydınlar and Koç Universities. This program included the physicians from the departments of general surgery, gastroenterology, pathology, radiology, nuclear medicine, medical oncology, radiation oncology, and medical genetics. The gray zones in the management of rectal cancer were determined by reviewing the evidence-based data and current guidelines before the meeting. Topics to be discussed consisted of diagnosis, staging, surgical treatment for the primary disease, use of neoadjuvant and adjuvant treatment, management of recurrent disease, screening, follow-up, and genetic counseling. All those topics were discussed under supervision of a presenter and a chair with active participation of related physicians. The consensus text was structured by centralizing the decisions based on the existing data.

Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation., Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety., Results: Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients., Conclusion: Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy., Materials and Methods: Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread., Results: There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)max, SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P < 0.001)., Conclusions: In the preoperative PET study inoperable lung adenocarcinoma cases, MTV/CTV ratio higher than 1 was found to predict STAS positivity. As a result, it was found that it provided significant clinical additional information regarding the need for a surgical approach (lobar resection instead of sublobar) and adjuvant chemotherapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

What Is Known and Objective: Erlotinib is a small molecule tyrosine kinase inhibitor which blocks the activation of epidermal growth factor receptor (EGFR), a transmembrane receptor that is upregulated in many cancer types. Inhibition of angiogenesis with consequent impairments in intratumoral microcirculation is one of the mechanisms through which EGFR inhibition halts the progression of cancer. A consequence of impaired microcirculation is intratumoral hypoxia, which results in increases in serum uric acid levels. The goal of this study was to investigate the relationship between serum uric acid levels and response to erlotinib in metastatic non-small-cell lung cancer (NSCLC)., Methods: A total of 56 patients with metastatic non-small-cell lung cancer who received erlotinib for a duration of at least 3 months were included in this retrospective cohort study. Demographic characteristics, progression status, baseline serum uric levels and 3-month serum uric acid levels were recorded and analysed., Results and Discussion: Of the study population, 21 (37.5%) were female and 35 (62.5%) were male patients. No significant difference in above demographic characteristics was observed among exitus, survivor with progression and survivor without progression groups. Patients who responded favourably to erlotinib with no progression of their disease had significantly increased uric acid levels at 3-month follow-up (P = .01). Such a correlation was not observed if the patient was exitus (P = .47) or had progressed on erlotinib therapy (P = .19)., What Is New and Conclusion: In conclusion, this study is the first to demonstrate significant increases in serum uric acid levels in patients with metastatic NSCLC who responded favourably to erlotinib and had no progression under erlotinib therapy. Further studies are required to confirm and characterize serum uric acid as a novel biomarker in predicting the outcome in those with metastatic NSCLC., (© 2019 John Wiley & Sons Ltd.)

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood., Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed., Study Design: Multicenter retrospective observational cohort study., Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer., Results: The median progression-free survival in our population was 7 months (25 th -75 th percentile, 4-10), and the median overall survival was 11 months (25 th -75 th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%)., Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Purpose: Awareness of advances in the nutritional aspects of cancer care and translation of this information into clinical practice are important for oncology practitioners to effectively couple oncologic and nutritional approaches throughout the cancer journey. The goal of this consensus statement by a panel of medical oncologists was to provide practical and implementable guidance addressing nutritional aspects of cancer care from the perspective of the medical oncologist., Methods: A panel of medical oncologists agreed on a series of statements supported by scientific evidence and expert clinical opinion., Findings: Participating experts emphasized that both poor nutritional intake and metabolic alterations underlie cancer-related malnutrition. The use of liquid and high energy-dense oral nutritional supplements may enable better patient compliance, whereas higher efficacy is more likely with the use of pharmaconutrient-enriched oral nutritional supplements in terms of improved weight, lean body mass, functional status, and quality of life, as well as better tolerance to antineoplastic treatment. A multimodal approach is currently believed to be the best option to counteract the catabolism leading to cancer-related malnutrition; this treatment is scheduled in parallel with anticancer therapies and includes nutritional interventions, multitarget drug therapies, and exercise and rehabilitation programs. Participating experts emphasized the role of the oncologist as a reference professional figure in the coordination of nutritional care for patients with cancer within the context of complex and different clinical scenarios, particularly for permissive-adjunctive nutritional support., Implications: This review article provides practical guidance addressing major nutritional aspects of cancer care from the medical oncologist's perspective. Thus, this document is expected to assist oncology practitioners in terms of awareness of advances in the nutritional aspects of cancer care and translation of this information into their clinical practice to effectively couple oncologic and nutritional approaches as part of the continuum of care for patients with cancer., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the extent of visceral pleural invasion (VPI) and its effect on survival along with its place in determining the T descriptor in TNM staging in our patients., Methods: A total of 233 patients underwent lung resection. The data were retrospectively analyzed in terms of sex, age, histopathologic type, stage of the tumor, extent of VPI, and survival. Patients who had neoadjuvant chemotherapy or chemoradiotherapy, distant metastasis, parietal pleural invasion, and operative mortality were excluded., Results: The median follow-up was 59 months (range 4-126). The extent of VPI was PL0 in 119 (65.7%) patients, PL1 in 47 (26%) patients, and PL2 in 15 (8%) patients. The median survival rates were 65 (range 43-96) months for PL0, 54 (range 37-72) months for PL1, and 39 (range 12-69) months for PL2. The 5-year overall survival rates were 74.7% for PL0, 77.8% for PL1, and 53.3% for PL2. There were statistically significant differences in overall survival among PL0, PL1, and PL2 ( p = 0.03). In subgroup analysis, the difference was insignificant in PL0 vs PL1 ( p = 0.81), but significant in PL0 vs PL2 ( p = 0.02) and PL1 vs PL2 ( p = 0.04) groups., Conclusions: This study emphasizes that the presence of VPI is related with poor prognosis independent of lymph node positivity, histologic subtypes, and tumor size. As the study shows, PL0 and PL1 have similar survival rates and these two groups may be considered as VPI (-) patients whereas PL2 disease affects survival outcomes.

Background: We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption., Methods: The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP)., Results: We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P < .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram-negative infections decreased (from 43% to 20%, P = .003). In the multivariate analysis, appropriate continuation or de-escalation or discontinuation was increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR, 0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased significantly., Conclusions: After implementation of the ASP, the case fatality rate among the patients with FN decreased. Appropriate antimicrobial use increased and overall antimicrobial consumption was reduced. Bacterial infections and Candida infections decreased., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.

Background: Desmoid tumors are uncommon and benign mesenchymal neoplasms. The optimal treatment of patients with desmoid tumors is still controversial. Surgery is the primary treatment for locally invasive or recurrent desmoid tumors. Also, radiotherapy is a treatment option for patients at high risk for local failure such as those with positive margins or recurrent and unresectable tumors., Aims: To report our institutional experience and long-term results of patients with desmoid tumors who received radiotherapy., Study Design: Retrospective cross-sectional study., Methods: Between 1980 and 2009, 20 patients who received radiotherapy (RT) in our institution were analyzed. The majority of patients (80%) were referred with a recurrent tumor after previous surgery. Thirteen patients underwent marginal resection, 4 had wide local excision and 3 patients had only biopsy. Resection margin was positive in 15 (75%) patients. All patients received radiation therapy. The median prescribed dose was 60 Gy. Five patients received less than 54 Gy., Results: The median follow-up time was 77.5 months (28-283 months). Nine patients developed local recurrence after RT. Seven local failures (78%) were in field. Time to local recurrence ranged from 3-165 months (median 33 months). The 2-5 year local control (LC) rates were 80% and 69%, respectively. On univariate analysis, the 5 year local control rate was significantly better in the patients treated with ≥54 Gy than in patients who received <54 Gy (p=0.023). The most common acute side effect was grade 1-2 skin toxicity. As a late side effect of radiotherapy, soft tissue fibrosis was detected in 10 patients and lymphangitis was seen in 1 patient. One patient developed radiation-induced sarcoma., Conclusion: According to our results, radiotherapy is especially effective in recurrent disease and provides a high local control rate in the patients received more than 54 Gy.

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Study Question: Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human?, Summary Answer: The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro., What Is Known Already: Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary., Study Design, Settings, Size and Duration: This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015., Participants/materials, Setting, Methods: Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups., Main Results and the Role of Chance: The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs., Limitations, Reasons for Caution: Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo., Wider Implications of the Findings: GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey., Methods: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab., Results: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050)., Conclusion: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.

Background/aims: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy., Methodology: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test., Results: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect., Conclusions: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

Background: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively., Materials and Methods: Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed., Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively)., Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Aims and Background: There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors., Methods and Study Design: From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics., Results: The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis., Conclusions: We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

We investigated predictive values of BRAF, PI3K and PTEN in cetuximab responses in KRAS wild-type (+) chemotherapy refractory, metastatic colorectal cancer (CRC) patients. Primary tumour tissues of 41 KRAS wild-type mCRC patients receiving cetuximab-based chemotherapy were investigated for PI3K, PTEN, KRAS and BRAF mutations. Progression-free survival (PFS) and overall survival (OS) periods were calculated with Kaplan-Meier method and the Cox proportional hazards model was used. PTEN and PI3K expressions were 63 and 42 %, respectively. BRAF mutation was observed as 9.8 % among patients. Tumours with BRAF mutation had statistically lower response rates (RR) for cetuximab-based treatment than tumours with BRAF wild type (0 vs. 58 %, p = 0.02). PTEN expressing tumours had statistically higher RR for cetuximab-based treatment than tumours with PTEN loss (42 vs. 12 %, p = 0.04). PI3K expression had worse significant effect on cetuximab RR than PI3K non-expressed tumours (15 vs. 44 %, p = 0.023). Median PFS was significantly longer in patients with PTEN expression (14 months) than in patients with PTEN loss (5 months) (HR, 0.4; p = 0.028). Median PFS was significantly longer in patients with PI3K non-expression (15.2 months) than in patients with PI3K expression (4.1 months) (HR, 0.31; p = 0.001). Significant difference in PFS and OS between patients with BRAF mutated and BRAF wild-type tumours was not detected. However, patients with PTEN expression had significantly longer OS (15.1 months) than patients with PTEN loss tumour (9.9 months) (HR, 0.34; p = 0.008). Patients without PI3K expression had significantly longer OS (18.2 months) than patients with PI3K expression (10.1 months) (HR, 0.27; p = 0.001). Multivariate analyses revealed that PTEN expression (HR, 0.48; p = 0.02) and absence of PI3K expression (HR, 0.2; p = 0.001) were independent prognostic factors for increased PFS. Similarly, PTEN overexpression (HR, 0.62; p = 0.03) and absence of PI3K expression (HR, 0.27; p = 0.005) were independent prognostic factors for increased OS. In PTEN loss, PI3K expression may be used as biomarkers to further select KRAS wild-type patients undergoing anti-epidermal growth factor receptor treatment.

Purpose: To compare the incidence and severity of acute and chronic hematologic toxicity (HT) in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for curative treatment of cervical cancer and to ascertain the dosimetric parameters of two techniques associated with acute and chronic HT., Materials and Methods: A total of 127 patients with cervical cancer receiving concomitant pelvic radiotherapy (RT) and cisplatin were evaluated. Pelvic bone marrow (BM) was contoured for each patient and divided into five sub-regions: lumbosacrum (LS), ilium (IL), lower pelvis (LP), pelvis (P), and whole pelvis (WP). The volume of each BM region receiving 10, 20, 30, and 40 Gy was calculated (V10, -V20, -V30, and -V40). The lowest level of hemoglobin, leukocyte, neutrophil, and platelet counts were obtained during chemoradiotherapy and six months after RT. The nadir values were graded according to Common Terminology Criteria for Adverse Events (version 3.0)., Results: Grade 2 or greater acute anemia, leukopenia, neutropenia, thrombocytopenia was observed in 2%, 41.5%, 12% ,and 0% in 3DCRT group and in 27%, 53%, 24.5%, and 4.5% in IMRT group, respectively. Grade 2 or greater chronic anemia, leukopenia, neutropenia, and thrombocytopenia was observed in 11%, 10%, 6%, and 0% in 3DCRT group and in 11%, 9%, 4.5%, and 0% in IMRT group, respectively. LS-V30, 40; IL-V10, 20, 30, 40; LP-V10, 20 ,40; P-V10, 20, 30, 40, and TP-V10, 20, 30, 40 were significantly reduced with IMRT planning compared to 3DCRT planning. Logistic regression analysis of potential predictors showed that none of the dosimetric parameters were significant for predicting acute and chronic HT., Conclusion: The present findings showed that IMRT planning reduced irradiated BM volumes compared to 3DCRT planning. However, no difference between the two techniques was observed in terms of acute and chronic HT. Further studies are needed to confirm these results.

Objective: To evaluate the long term results among patients with soft tissue sarcoma of the thoracic wall., Materials and Methods: Twenty-six patients who were treated with pre-or postoperative radiotherapy between December 1980-December 2007, with a diagnosis of soft tissue sarcoma of the thoracic wall were retrospectively evaluated., Results: The median age was 44 years (14-85 years) and 15 of them were male. A total of 50% of patients were grade 3. The most common histologic type of tumor was undifferentiated pleomorphic sarcoma (26.9%). Tumor size varied between 2-25 cm (median 6.5 cm). Seventeen of the cases had marginal and 9 had wide local resection. Four cases received preoperative radiotherapy and 22 postoperative radiotherapy. Six of the patients with large and high grade tumors received chemotherapy. Median follow-up time was 82 months (9-309 months). Local recurrence and metastasis was detected in 34.6% and 42.3% of patients, respectively. Five- year local control (LC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) were 62%, 38%, 69%, and 76% respectively. On univariate analysis, the patients with positive surgical margins had a markedly lower 5-year LC rate than patients with negative surgical margin, but the difference was not significant (43% vs 78%, p=0.1). Five-year DFS (66% vs 17%) and DSS (92% vs 60%) rates were significantly worse for the patients who had high grade tumors (p=0.01, p=0.008 respectively)., Conclusions: Tumor grade and surgical margin are essential parameters for determining the prognosis of thoracic wall soft tissue sarcoma both in our series and the literature.

Background: To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities., Materials and Methods: Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses., Results: Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7%, 47%, 69.8%, and 80%, 60%, 60% in the chemoradiotherapy and radiotherapy groups, respectively. On univariate analysis, patients who were treated with hypofractionation experienced significantly superior LC, DFS and CSS rates with similar rates of late toxicity when compared with patients who were treated with conventional fractionation and statistical significance was retained on multivariate analysis., Conclusions: Treatment results are consistent with the literature. As neoadjuvant chemoradiotherapy provides effective LC and CSS with acceptable morbidity, it should be preferred for patients with large and borderline resectable STS.

Intraglomerular metastasis is a very rare condition with an underlying cause that is not yet well understood. We present the 18F-FDG PET/CT images of histologically proven intraglomerular metastases from newly diagnosed malignant melanoma with positive sentinel lymph node metastases. During the initial diagnostic evaluation period, the patient also had a sudden increased serum creatinine level. FDG PET/CT demonstrated diffuse glomerular FDG uptake unlike typical physiologic pelvicaliceal activity. Renal biopsy revealed diffuse crescentic lesions containing metastatic melanoma cells.

Background/aims: Cetuximab is currently approved for the treatment of metastatic colorectal cancer (mCR) with KRAS wild-type. Prior few studies demonstrated that G13D mutated tumors could benefit from cetuximab. This study aims to investigate whether KRAS G13D mutated tumors benefit from cetuximab in the chemotherapy refractory patients., Methodology: We retrospectively compared progression-free survival (PFS), overall survival (OS) and response rate (RR) according to KRAS mutation status in 105 patients with mRC treated at the Cerrahpasa Medical School Hospital, between October 2008 and October 2011, with cetuximab alone or in combination with chemotherapy., Results: PFS was significantly longer in patients G13D mutated tumors (6.81 months) than in patients with other KRAS mutated tumors (5 months) (p=0.027). No significant difference in PFS between patients G13D mutated and KRAS wild-type tumors was detected. No significant difference in OS was detected in patients between G13D mutated tumors and other KRAS mutated tumors. However, patients with KRAS wild-type tumors had significantly longer OS (16.1 months) than patients with mutated tumors (8.9 months) (p=0.025). RR in patients with other KRAS mutated tumors, was significantly worse than those with G13D mutated tumors (p=0.002)., Conclusion: Our study demonstrated an association between the presence KRAS G13D mutanted and survival chemotherapy in refractory metastatic colorectal cancer treated with cetuximab.

Delftia tsuruhatensis is a non-glucose fermenting, oxidase positive, motile, gram-negative bacillus first isolated from activated sludge collected from a domestic wastewater treatment plant in Japan. To the best of our knowledge only one case of infection with Delftia tsuruhatensis exists in the medical literature. This is the second case report of human infection having Delftia tsuruhatensis as a causative agent.

Background: Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal system. The most common primary site of GIST is the stomach. The treatment is primarily surgery, and the standard medical therapy is imatinib. Long-term survival can be obtained with good follow-up and treatment., Materials and Methods: In this study, data entry was performed using a web-based patient registry system for patients who were referred to 3 centers and retrospectively were diagnosed with GIST., Results: The study cohort consisted of 249 patients, including 160 men (64.3%) and 89 women (35.7%). The mean age was 59 years (range 21-90 years). Initially, 69.9% of the patients had local disease, while 30.1% had metastatic disease. The tumor was located in the stomach in 45.6% of patients. According to the Fletcher risk classification, the very low risk group included 8 subjects (3.2%), the low risk group included 40 subjects (16.1%), the moderate risk group included 56 subjects (22.5%), and the high risk group included 117 subjects (47%); the unspecified group included 28 subjects (11.5%)., Conclusion: These data are important for revealing the clinicopathologic characteristics and survival data of patients with GIST, who are treated and followed up in Turkey., (Copyright © 2013 S. Karger AG, Basel.)

Background: We aimed to test the hypothesis that whether FDG-PET/CT which was ordered for various purposes can predict suspected or particularly unsuspected bone marrow metastasis (BMM) from the complete blood count and therefore can change the management of these patients., Methods: In this retrospective study, the study sample consisted of 68 subsequent patients presented to our institution's pathology department with bone marrow metastases of solid tumors. PET/CT was found to have been ordered in 10 out of 68 patients (6.8%) for various purposes. All patients gave informed consent about the PET/CT examinations and bone marrow biopsies., Result: FDG-PET/CT was ordered in 10 out of 68 solid tumor patients with pathologically proven BMM. Of these 10 patients, 3 were female and 7 were male; mean age was 54.7 years. While FDG PET/CT showed bone and BMM in 4 of 10 patients (40%), the rest of the patients had BMM without bone involvement. Five patients (50%) who had probable bone marrow involvement on their FDG PET/CT scans had unsuspected complete blood counts with regard to BMM., Conclusion: PET/CT has the ability to detect a substantial number of metabolically active tumor cells in the bone marrow in all of our patients which we proved by bone marrow biopsies. We think that this cohort of patients with solid tumors is hypothesis-generating with regard to detecting early bone marrow metastases by FDG PET/CT., Competing Interests: The authors have declared no conflicts of interest.

Introduction: Gastrointestinal stromal tumors are rare tumors. They commonly metastasize within the abdominal cavity, particularly to the liver. Less commonly, metastases can be found in the bone., Case Presentation: We here present a case of metastasis to the scapula in a 54-year-old Caucasian male patient with an advanced gastrointestinal stromal tumor, which was subsequently successfully treated with resection and sunitinib., Conclusion: The present study is, to the best of our knowledge, the second to describe scapular metastasis of a gastrointestinal stromal tumor. Our patient was treated by scapulectomy. The overwhelming majority of scapular tumors are metastases that arise from soft tissue, hepatocellular and thyroid tumors. Gastrointestinal stromal tumor metastasis occurs rarely. Scapular surgery can successfully provide local control of the disease. After the surgery, patients should continue with medical treatment.

We describe here a patient with a metastatic malignant melanoma displaying crescentic lesions in the glomeruli. A 64-year-old woman was referred to our hospital because of a sudden increase of serum creatinine. Clinical diagnosis suggested rapidly progressive glomerulonephritis. Renal biopsy revealed diffuse crescentic lesions containing metastatic melanoma cells. These cells were also seen in the glomerular capillary lumina and tubules, and a few scattered tumor cells were also present in the interstitium. Glomerular metastasis is a very rare entity. To the best of our knowledge, this patient is the first to be described in the English language literature showing intraglomerular metastasis of malignant melanoma as demonstrated by needle biopsy and is only the second patient with intraglomerular metastasis presenting with acute renal failure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Bisphosphonates (BSPs) are used for the treatment of multiple myeloma, metastatic breast and lung cancer, Paget's disease, osteoporosis, hypercalcemia due to malignancy, and many other skeletal diseases. BSPs reduce osteoclastic functions, which result in bone resorption. Bisphosphonates-related osteonecrosis of jaws (BRONJ) is a newly developed term that is used to describe the significant complication in patients receiving bisphosphonates. BSPs are known to exhibit an anti-angiogenetic effect that initiates tissue necrosis of the hard tissue. There is currently no consensus on the correct approach to this issue. The aim of this retrospective study is to compare the effects of laser surgery with biostimulation to conventional surgery in the treatment of BSP-induced avascular bone necrosis on 20 patients who have been treated in our clinic. BRONJ was evaluated in patients with lung, prostate, and breast cancer under intravenous BSP treatment. Twenty patients in this study developed mandibular or maxillary avascular necrosis after a minor tooth extraction surgery or spontaneously. Bone turnover rates were evaluated by serum terminal C-telopeptide levels (CTX) using the electrochemiluminescence immunoassay technique and patients were treated with laser or conventional surgical treatments and medical therapy. Ten patients were treated with laser surgery and biostimulation. An Er:YAG laser (Fotona Fidelis Plus II® Combine laser equipment, Slovenia) very long pulse (VLP) mode (200 mJ, 20 Hz) using a fiber tip 1.3 mm in diameter and 12 mm in length was used to remove the necrotic and granulation tissues from the area of avascular necrosis. Biostimulation was applied postoperatively using an Nd:YAG laser. Low-level laser therapy (LLLT) was applied to the tissues for 1 min from 4 cm distance using an Nd:YAG laser (Fotona-Slovenia) with a R24 950-µm fiber handpiece long-pulse (LP) mode, 0.25-W, 10 Hz power/cm(2) from the mentioned distance the spot size was 0.4 cm(2), and power output was 2.5 J. Energy density from the mentioned distance was calculated to be 6.25 J/cm(2). The other ten patients were treated with conventional surgery. Treatment outcomes were noted as either complete healing or incomplete healing. There were no statistically significant differences between laser surgery and conventional surgery (p > 0.05). CTX values also did not affect the prognosis of the patients. Treatment outcomes were significantly better in patients with stage II osteonecrosis than in patients with stage I osteonecrosis. Our findings suggest that dental evaluation of the patients prior to medication is an important factor in the prevention of BRONJ. Laser surgery is a beneficial alternative in the treatment of patients with this situation. Further randomized studies with larger patient numbers may also improve our understanding of treatment protocols for this situation.

We report a 53-year-old male patient who underwent paravertebral mass excision at the D10-11-12 vertebral levels in 2007. The histopathological evaluation of the mass showed the presence of neuroblastoma. The patient was diagnosed with stage IV neuroblastoma. He received 6 courses of chemotherapy and exhibited a stable course until March 2010. When he was reevaluated in March 2010, progression in the metastatic lesion as well as local recurrence was detected. The patient, who was restarted on chemotherapy, developed progressive weakness and loss of sensation of the lower extremity. The neurosurgical investigation revealed an irreversible loss in motor functions. The patient is currently on symptomatic treatment.

A 37-year-old woman presented to the Internal Medicine Clinic with complaints of abdominal pain and constipation which had begun 3 months earlier. A colonoscopy was performed, and wall thickening of the sigmoid colon was detected. A biopsy of the sigmoid colon revealed a poorly differentiated, mucin-producing adenocarcinoma with a signet-ring pattern. No distant metastasis was detected. The patient was treated with chemotherapy consisting of 5-fluorouracil, leucovorin, and oxaliplatin. One and a half years later, a painless mass, which was not fixed to the skin, measuring 1 cm in diameter, was found in the lower outer quadrant of the left breast. A core biopsy of the mass was performed, and a histopathological report confirmed metastasis to the breast from mucinous adenocarcinoma of an intestinal primary.

Objective: Osteosarcoma of the bone accounts for approximately 20% of all primary malignant bone tumors. Most cases (75-85%) are high-grade osteosarcomas. We aimed to introduce low-grade osteosarcomas that we found by retrospectively scanning our archives because of the diagnostic difficulties, rarity and different therapeutic approach required., Material and Method: We found 156 osteosarcoma cases in the archives of the Department of Pathology of Istanbul University, Cerrahpaşa Faculty of Medicine covering the period 2000 to 2010. These cases included 141 high-grade and 15 low-grade osteosarcomas., Results: Low-grade osteosarcomas made up 10.4% of all osteosarcomas. Age and sex distribution were 19 to 54 (median 33.6) with 9 females and 6 males. Most cases were located in the distal femur while others were in the proximal tibia, the left wrist, the distal tibia and the right knee. The tumors were generally made up of relatively well-formed trabeculae of woven bone surrounded by a moderately cellular spindle cell proliferation entangled in collagen fibers. Thirteen cases were reported as parosteal osteosarcoma, one as intramedullary well-differentiated osteosarcoma, and one as low-grade osteosarcoma metastasis in the lung., Conclusion: Low-grade osteosarcomas account for approximately 3-5% of all osteosarcomas. They are more commonly seen in women and 9 cases out of 6 were female in our series. The average age was 33.6 (19-54). The distal femur was the most common localization as is typical in osteosarcomas. In contrast to high-grade lesions, surgery will be sufficient in low-grade osteosarcomas. The survival rate ranges from 90% to 100%. Differentiating low-grade osteosarcomas from high-grade osteosarcomas and benign lesions and using a multidisiplinary approach for the diagnosis, treatment and follow-up periods are of vital importance.

Objective. The aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas. Study Design. Retrospective record review. Setting. Istanbul University, Cerrahpasa Medical Faculty, medical oncology outpatient clinic. Subjects and Methods. There were 3 stage A tumors, 5 stage B and 11 stage C according to the Kadish staging system. There were 5 grade I/II and 12 grade III/IV according to the Hyams' histopathologic system. Involvement to orbita was detected in eight patients at the time of diagnosis. Results. The median follow-up period was 23.7 months. The 5-year survival rate for the whole group was 26%. The stage A/B groups exhibited a better survival rate than the C group with 2-year survival rates being 25 versus 71% respectively (P = .008). The grade I/II groups exhibited a better survival rate than the grade III/IV groups with 2-year survival rates being 50 versus 16% respectively (P = .001). The group who had orbital involvement exhibited a poor survival rate than the group of patients who had no involvement of the orbital. Conclusion. In our study, tumor stage, histopathologic grading, involvement of the orbita, brain and bone marow metastases were the statistically significant prognostic factors.

Introduction: Primitive neuroectodermal tumors (PNETs) are rare, rapidly progressive, small- round cell tumors with a poor prognosis despite multimodal therapy, including surgery and chemoradiotherapy. The treatment of choice was unknown since no clinical series with surgical therapy had been reported. We evaluated the impact of multimodal treatment in patients with PNETs located in the thoracic region., Methods: Between 1998 and 2006, 25 patients with PNETs in the thoracic region were treated in 3 tertiary-care hospitals. The patients consisted of 15 males and 10 females with a mean age of 27.2 years (range, 6-60). The tumor was in the chest wall in 20 (involving the costovertebral junction in 9), the lung in four, and the heart in one patient. Twelve patients received neoadjuvant chemotherapy (54.5%), and 22 of 25 patients underwent surgery., Results: In patients who received neoadjuvant treatment, the mean regression rate was 65.4% (range, 30-100%). Eighteen (82%) patients underwent chest wall resection, while 7 (32%) had vertebral resections, and the remaining 4 (16%) had pulmonary resections. A complete resection was possible in 18 of 22 patients (82%). Patients with incomplete and complete resections had 25% and 56% 5-year survival rates, respectively (p = 0.13). The progression-free 3-year survival rate was 36% and the median survival time was 13 months. The complete resection rate was significantly higher in patients receiving neoadjuvant therapy (p = 0.027). The 5-year survival rate of the patients with or without neoadjuvant therapy was 77% and 37%, respectively (p = 0.22) although it prolonged the disease-free survival (p = 0.01). The 5-year survival rate of patients without costovertebral junction involvement was 66%, whereas patients with PNETs involving the costovertebral junction had a 21% 3-year survival. The difference was statistically significant (p = 0.01). The 5-year progression-free survival rate of patients without costovertebral junction involvement was 58%, whereas patients with PNETs involving the costovertebral junction had a 14% 1-year progression-free survival (p = 0.004)., Conclusions: PNET is an aggressive malignancy that often requires multimodal therapy. Induction chemotherapy leads to a greater complete resection rate and better disease-free survival, while involvement of the costovertebral junction indicates a poorer survival.

Purpose: To determine the role of clinical examination, ultrasonography (US), and magnetic resonance imaging (MRI) in detecting local tumor recurrence in patients who underwent modified radical mastectomy for breast cancer., Materials and Methods: The study included 27 patients who were examined between April 1999 and April 2003. US evaluation of the chest wall was performed in all patients. MRI was performed on 10 patients due to suspicious findings in clinical examination, on 3 patients due to US findings, and on 8 patients due to both US and clinical examination findings. Six patients without any suspicious findings underwent MRI for follow-up purposes. The lesions detected with MRI were evaluated according to their morphology, contrast enhancement characteristics and dynamics. The focal lesions that enhanced intensely at the early phase were accepted as suspicious for malignancy., Results: Of the 10 cases that underwent biopsy secondary to suspicious lesions for malignancy according to MRI findings, 7 were found to have recurrence. In the remaining 3 patients, recurrence diagnosis was made based on the fact that the lesions regressed in response to chemotherapy. In 17 cases, there were no suspicious findings on MRI for local recurrence. In 2 of these cases, biopsies were performed due to suspicious US findings; however, no malignancies were detected. The sensitivity and specificity of clinical examination in detecting local recurrence was 70% and 35.2%, respectively. These values were 90% and 88.2% for US, and 100% and 100% for MRI., Conclusion: In patients with mastectomy, US and MRI were more successful in detecting local recurrence than clinical examination. Considering the fact that US is cheaper and more readily available than MRI, it should be part of the routine follow-up in order to detect local recurrence early. MRI will be helpful in cases with suspicious US findings by increasing the specificity of the evaluation as well as determining the actual size and spread of any lesions, which is valuable information for the subsequent management and response to the particular treatment.

Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the PNET/Ewing's sarcoma family. We hereby report a case of PNET of the ovary, which was detected at the second trimester of pregnancy. Chemotherapy was administered and a healthy baby was delivered by cesarean section. After the pregnancy, the mother was found to have metastatic disease. Chemotherapy was continued, but she died due to progressive disease 13 months after the initial diagnosis. In this case report, we discuss chemotherapy options during pregnancy and the importance of multidisciplinary approach to unusual presentations of rare tumors.

Aim: To establish whether there is a correlation between angiogenesis and metastasis in primary cutaneous melanoma (PCMM)., Methods: We studied the microvessel density and the expression of vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) in 22 cases of PCMM with metastasis at presentation (metastatic group) and 28 cases of PCMM without metastasis for 24 months or more (non-metastatic group). Microvessels were stained with CD31/PECAM-1 antibody and counted. We assessed the proportion of VEGF expression in tumour cells, lymphocytes infiltrating the tumour (TIL) and lymphocytes at the periphery of the tumour, as well as the proportion of bFGF expression in tumour cell cytoplasms, nuclei and intra- and peritumoral vessels., Results: An increased microvessel density was detected in the metastatic group (15-33 [24.09 +/- 5.55] versus 2-24 [12.96 +/- 6.02]). Moreover, enhanced expression of VEGF in tumour cells and peritumoral lymphocytes (Chi-square p = 0.038 and p = 0.018) and bFGF in peritumoral vessels (chi(2) p = 0.013) correlated with the simultaneous presence of melanoma metastasis in PCMM. Furthermore, microvessel density was correlated with the expression of bFGF in peritumoral vessels (rs = 0.53, p = 0.049) and VEGF in tumour cells (rs = 0.37, p = 0.019)., Conclusion: Microvessel density as well as the expression of both VEGF and bFGF might be informative concerning the progression of melanoma.

Background and Purpose: To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients., Patients and Methods: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months)., Results: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment., Conclusion: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

Purpose: To assess the role of preoperative radiotherapy in patients with nonmetastatic high-grade osteosarcoma of the extremities for limb-sparing surgery and to compare the response of neoadjuvant therapies, local control, and survival with the literature results., Methods and Materials: Forty-six patients with osteosarcoma of the limbs who were treated within a limb salvage protocol including preoperative radiotherapy and chemotherapy between 1987 and 2002, were retrospectively analyzed. Median age was 17 years (range, 14-66 years). Treatment was started with neoadjuvant chemotherapy. Cisplatin, epidoxorubicin, ifosfamide, and methotrexate were used in different combinations. Preoperative radiotherapy was applied, usually between the second and third cycle of chemotherapy. Radiotherapy was given (35 Gy in 10 fractions) to 44 patients. Two patients were treated with 46 Gy at 2 Gy/day. Definitive surgery was administered after the third course of chemotherapy. Chemotherapy was complete 6 courses postsurgery., Results: Median follow-up time was 44 months (range, 2-154 months). Forty-four patients had limb-sparing surgery, whereas 2 had amputation. Tumor necrosis rate was >/=90% in 87% of the patients (Huvos Grade 3-4). Two patients had local failures, and 26 patients (56.5%) had distant metastases. The 5-year local control and overall survival rates were 97.5% and 48.4%, respectively. On univariate analysis, age

Epidural spinal metastasis of Ewing's sarcoma is rarely observed. We report on a rare case of purely epidural spinal metastasis of Ewing's sarcoma with pain and paraplegia, and describe the treatment and final outcome of the patient.

Paecilomyces variotii was isolated from two subsequent cerebrospinal fluid (CSF) specimens of a cancer patient. Identification was confirmed through beta-tubulin and rDNA ITS sequencing. MICs were determined for seven antifungal agents; the isolate was found to be susceptible to amphotericin B (AMB), itraconazole (ITZ), ketaconazole (KTZ) and 5-fluorocytosine (5FC) but resistant to fluconazole (FLZ) and miconazole (MCZ). Despite antimycotic therapy, the infection proved to be fatal.