Multi-institutional analysis of extracranial oligometastatic colorectal cancer patients treated with stereotactic body radiation therapy: TROD 02-008 study.

PURPOSE: To investigate the treatment outcomes of extracranial oligometastatic colorectal cancer (CRC) patients treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The clinical data of 388 extra-cranial oligometastatic CRC (≤ 5 lesions) patients and 463 lesions treated with SBRT at 19 cancer institutions were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local control (LC) were assessed in uni- and multivariable analyses. RESULTS: The median age was 62 years (range, 29-92 years). The majority of the patients (90.5%) received surgery and systemic treatment for their primary tumor, had ≤ 2 metastasis (83.3%), had single organ involvement (90.3%), and staged using flouro-deoxyglucose positron emission tomography (FDG-PET/CT) (76%). The median fraction and total radiation doses were 10 Gy (range: 6-34 Gy) and 50 Gy (range: 8-64 Gy), respectively, delivered in a median of 4 fractions (range: 1-8). The median follow-up time for the entire cohort was 30.7 months (interquartile range: 27.0-34.3 months). The 3­year OS, PFS, and LC rates were 64.0%, 42.3%, and 72.7%, respectively. The 3­year LC rate was significantly higher in patients receiving BED10 ≥ 100 Gy than those receiving BED10 < 100 Gy (76.0% vs. 67.3%; p = 0.04). The 3­year PFS and OS rates were higher in patients receiving BED10 ≥ 100 Gy than those receiving BED10 < 100 Gy (33.2% vs. 25.2%; p = 0.03; 53.7% vs.  44.8%; p = 0.02). Single metastasis and complete response after SBRT were independent prognostic factors for survival in multivariable analysis. CONCLUSIONS: In this multi-center study, we demonstrated that SBRT is an effective treatment option of metastatic lesions in oligometastatic CRC patients by providing promising LC rates. Higher SBRT doses beyond BED10 ≥ 100 Gy were associated with improved LC and survival. LC of treated lesion and lower tumor burden after SBRT were associated with better outcomes.

Radiotherapy for vertebral hemangioma: the single-center experience of 80 patients.

PURPOSE: This study aimed to evaluate the therapeutic effect of radiotherapy and to determine possible prognostic factors in patients with painful vertebral hemangioma. METHODS: In the last two decades, 80 patients with vertebral hemangioma who received radiotherapy in our institute were evaluated in terms of pain response, treatment-related side effects, and prognostic factors. All patients were questioned 3 months after radiotherapy for the evaluation of pain response and were divided into three groups (complete response, partial response, and no change). Moreover, the visual analog scale (VAS) was used for pain response assessment in 46 patients. Pain status was assessed to detect recurrence at each clinical examination during the follow-up period. Possible prognostic factors such as gender, size of the hemangioma, location, multilevel involvement and additional musculoskeletal disease on pain response were analyzed. RESULTS: In this study, 45 individuals had lesions in the lumbar spine, 28 in the thoracic, and 7 in the cervical region. Furthermore, 51 patients had additional musculoskeletal conditions such as disc herniation, degenerative diseases, spondylolisthesis, and compression fracture. Radiotherapy was performed with a median daily dose of 2 Gy and a median total dose of 40 Gy. Complete pain response occurred in 58.8% of patients, 26.2% of patients had partial pain response, and 15% of patients had no pain response. The overall response rate was 85%, and 7 patients showed recurrent pain symptoms in the overall response group at routine follow-up. Additional musculoskeletal disorders were found to be the only prognostic factor associated with pain response. The median follow-up time was 60 months. Secondary malignancy was not found in any of the patients in this short follow-up time. No acute or late radiation-associated side effects greater than grade II were observed. CONCLUSION: To our best knowledge, this study is one of the largest single-institution radiotherapy series on vertebral hemangiomas reported to date. The obtained data support the efficacy and safety of radiotherapy in the treatment of painful vertebral hemangioma. Our study showed that additional musculoskeletal disease plays an important role in pain response. Other prognostic factors and treatment of vertebral hemangioma with stereotactic radiosurgery should be investigated in future studies.

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

PURPOSE: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era. METHODS: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT. RESULTS: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5­year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10. CONCLUSIONS: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

Activation of neuroimmune pathways increases therapeutic effects of radiotherapy on poorly differentiated breast carcinoma.

Recent studies document the importance of neuronal dysfunction in cancer development and metastasis. We reported previously that both depletion of neuropeptides in capsaicin-sensitive sensory nerve endings and vagotomy increases metastasis of triple negative breast carcinoma. Of the sensory neuropeptides, Substance P (SP) is distributed widely for regulation of immune functions. We therefore examined the affects of continuous exposure to low doses of SP on brain metastatic cells of the mouse breast carcinoma (4TBM) in the presence of radiotherapy (RT) thought to increase antigenicity of cancer cells. 4TBM cells have a cancer stem cell phenotype and induce extensive visceral metastasis after orthotopic inoculation into the mammary pad. Results demonstrated that SP treatment decreases the number of tumor-infiltrating myeloid-derived suppressor cells as well as the TNF-α response to LPS challenge. SP also increased CD4+Cd25(bright) cells in draining lymph nodes of tumor-bearing animals and IFN-γ secretion from leukocyte culture prepared from lymph nodes and spleens of tumor-bearing animals. SP also prevented tumor-induced degeneration of sensory nerve endings and altered release of angiogenic factors from cancer-associated fibroblasts (CAF) and tumor explants. In accordance with these observed immunological effects, combination treatment of continuous SP with a single dose of RT induced complete tumor regression and significantly reduced or prevented metastasis in 50% of the animals while suppressing primary tumor growth and metastasis in the remaining mice. These original findings demonstrate that SP through neuroimmune modulation can prevent formation of immune suppression in the tumor microenvironment, enhance cytotoxic immunity in the presence of RT and prevent metastatic growth.

The Predictive Role of Inflammatory Biomarkers in Patients With Larynx Cancer Undergoing Definitive Radiotherapy.

Inflammation plays an important role in the process of cancer development. The number of studies evaluating the ability of inflammatory biomarkers to predict survival has increased in recent years. This study aimed to comprehensively evaluate the predictive role of inflammatory biomarkers in patients with larynx cancer undergoing definitive radiotherapy. A total of 101 patients who underwent definitive radiotherapy for larynx cancer at our center were retrospectively examined. Blood samples were taken from the patients before radiotherapy to obtain biomarkers such as C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune inflammatory value (PIV), hemo-eosinophil inflammation index (HEI), albumin, and Lactate dehydrogenase (LDH). The study examined the predictive value of parameters for progression-free survival (PFS), local recurrence-free survival (LRFS), and overall survival (OS) using both univariate and multivariate Cox regression analysis. In the univariate analysis, the biomarkers that predicted PFS were SII, PIV, CRP, and Eastern Cooperative Oncology Group Performance Status (ECOG PS). According to the multivariate analysis, only CRP was found to be a significant predictor of PFS. In the univariate analysis, the following biomarkers were found to predict OS: NLR, PLR, MLR, SII, PIV, CRP, HEI, stage, and ECOG PS. In the multivariate analysis, NLR and ECOG PS were found to be predictors of OS. A significant difference was found in MLR, PIV, and CRP values based on the presence of lymphatic metastasis. The current study is the first to comprehensively examine the relationship between larynx cancer and several inflammatory biomarkers. Many of these biomarkers have been shown to predict both PFS and OS in patients with larynx cancer undergoing definitive radiotherapy. It has been shown that PIV and CRP may predict the presence of lymphatic metastases in addition to PFS and OS.

Comparison of Doses to Parotid, Temporomandibular Joint, and Pharyngeal Constrictor Muscles Using Different Techniques in Radiotherapy for Oropharyngeal Cancer.

OBJECTIVE: The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT) and helical tomotherapy (HT). The study examined several parameters, including target coverage, organs at risk, integral dose, and beam on time. Additionally, the study evaluated the doses to the parotid, temporomandibular joint, and pharyngeal constrictor muscles, which are important for swallowing. METHOD: The present study retrospectively analyzed the data of 13 patients with oropharyngeal cancer who underwent radiotherapy between 2019 and 2021. The treatment plans for each patient were regenerated using both sIMRT and HT treatment planning systems with the sequential boost method. The techniques were evaluated and compared based on dose-volume histogram, homogeneity index, and conformity index parameters. The target coverage and organs at risk were statistically compared for two techniques. Additionally, the doses received by the healthy tissue volume were obtained for integral dose evaluation. The beam on time for each technique was assessed. RESULTS: When considering planning target volume evaluation, there was no difference in Dmeans between the two techniques and sIMRT demonstrated higher D2% values compared to the HT. The HT technique had better results for all organs at risk, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle. As for integral dose, it has been shown that the sIMRT technique provides better protection compared to HT. In addition, the beam on time was also longer with the HT technique. CONCLUSION: Both techniques may provide optimal target coverage for patients with oropharyngeal cancer. HT conferred notable advantages, especially with regard to critical structures implicated in swallowing, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle, in comparison to sIMRT.

Differential characteristics of heart, liver, and brain metastatic subsets of murine breast carcinoma.

Breast carcinoma is comprised of heterogeneous groups of cells with different metastatic potential. To develop effective therapeutic strategies targeting metastatic disease, it is crucial to understand the characteristics of breast cancer cells that enable metastasis to distant organs. 4THM breast carcinoma cells are the cells of 4T1 primary tumors that metastasized to the heart. Cells of 4THM tumors which metastasized to liver (4TLM) were previously isolated. Recently macroscopic brain metastasis in 4THM injected animals, were isolated to obtain a brain metastatic cell line (4TBM). Using an orthotopic mouse model differential characteristic of cells metastasized to heart (4THM), liver (4TLM), and brain (4TBM) were compared for ability to metastasize and expression of stem cell markers. We found that 4TLM cells produced significantly more lung and liver metastasis compared to 4TBM and 4THM cells. In vitro, proliferation as well as migration rate of 4TLM cells was also significantly higher than the other cell lines. Remarkably primary tumors formed by 4TLM cells expressed significant amounts of CD34, a marker for mesenchymal malignancies. Markers of epithelial-mesenchymal transition were expressed in all metastatic cells, but the degree of expression differed. Majorities of 4TLM, 4THM, and 4TBM cells were CD44+ CD24- whereas, 12 % of 4TLM cells also expressed membranous CD24. Conditioned mediums of non-metastatic 67NR breast tumors and cancer-associated fibroblasts inhibited growth of highly metastatic 4TLM cells. Malignant cells metastasized to brain were distinguished by membranous E-cadherin expression that was markedly higher in 4TBM cells grown as spheroids suggesting E-cadherin is required for brain metastasis. Differential features of heart, brain, and liver metastatic cells in a syngenic model was shown in this study for the first time. These findings not only provide a model to explore new treatment modalities, but also demonstrate differential features of cancer cells that originally homed to a certain organ, such as liver or brain.

Olvanil activates sensory nerve fibers, increases T cell response and decreases metastasis of breast carcinoma.

BACKGROUND: Inactivation of sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) enhances breast cancer metastasis. Sensory neurons have profound effects on immune response to a wide range of diseases including cancer. Hence, activation of sensory nerves using feasible approaches such as specific TRPV1 agonists may inhibit breast cancer metastasis through neuroimmune pathways. TRPV1 agonists are considered for the treatment of pain and inflammatory diseases. METHODS: We here first determined the effects of four different TRPV1 agonists on proliferation of three different metastatic breast carcinoma cells since TRPV1 is also expressed in cancer cells. Based on the results obtained under in-vitro conditions, brain metastatic breast carcinoma cells (4TBM) implanted orthotopically into the mammary-pad of Balb-c mice followed by olvanil treatment (i.p.). Changes in tumor growth, metastasis and immune response to cancer cells were determined. RESULTS: Olvanil dose-dependently activated sensory nerve fibers and markedly suppressed lung and liver metastasis without altering the growth of primary tumors. Olvanil (5 mg/kg) systemically increased T cell count, enhanced intra-tumoral recruitment of CD8+ T cells and increased IFN-γ response to irradiated cancer cells and Con-A. Anti-inflammatory changes such as increased IL-10 and decrease IL-6 as well as S100A8+ cells were observed following olvanil treatment. CONCLUSIONS: Our results show that anti-metastatic effects of olvanil is mainly due to activation of neuro-immune pathways since olvanil dose used here is not high enough to directly activate immune cells. Furthermore, olvanil effectively depletes sensory neuropeptides; hence, olvanil is a good non-pungent alternative to capsaicin.

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study.

INTRODUCTION: In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated. MATERIALS AND METHODS: Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated. RESULTS AND CONCLUSION: No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.

The results of adjuvant radiotherapy in endometrial carcinoma.

AIM: To examine the clinical characteristics and treatment outcomes in patients with endometrial cancer receiving adjuvant radiotherapy. METHODS: A total of 157 patients who received postoperative radiotherapy (RT) between 1999 and 2008 were evaluated, retrospectively. The mean age was 59 years (34-82). All patients received RT following surgery. Stage distribution was as follows: 92 patients (59%) stage I, 21 patients (13%) stage II, and 44 patients (28%) stage III. RESULTS: Overall survival rate was 95% at 2 years and 84% at 5 years. By the end of follow up, 135 patients (86%) were disease-free, and 4 (2%) were alive with disease. Univariate and multivariate analyses identified stage, grade, and serosal involvement as significant predictors for overall survival. CONCLUSION: The results of our study suggests that early stage, low-grade endometrial cancer with no serosal involvement is associated with a better survival and adjuvant radiotherapy is a well tolerated and effective therapeutic option.

HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators.

Heat shock protein 90 (HSP90) inhibitors are considered as new radiosensitizing agents. PU-H71, a novel HSP90 inhibitor, is under evaluation for the treatment of advanced cancer. It is however not known whether PU-H71 alters radiosensitivity of metastatic breast cancer. Hence, we here evaluated mechanisms of possible anti-tumoral and radiosensitizing effects of PU-H71 on breast carcinoma cells metastasized to vital organs such as the liver and brain. The effect of PU-H71 on proliferation of breast carcinoma cells was determined using 4T1 cells and its brain (4TBM), liver (4TLM), and heart (4THM) metastatic subsets as well as non-metastatic 67NR cells. Changes in radiation sensitivity were determined by clonogenic assays. Changes in client proteins and levels of angiogenic and inflammatory mediators from these cancer cell cultures and ex vivo cultures were detected. PU-H71 alone inhibited ERK1/2, p38, and Akt activation and reduced N-cadherin and HER2 which further documented the anti-tumoral effects of PU-H71. The combination of PU-H71 and radiotherapy induced cytotoxic effect than PU-H71 alone, and PU-H71 showed a radiosensitizing effect in vitro. On the other hand, PU-H71 and radiation co-treatment increased p38 phosphorylation which is one of the hallmarks of inflammatory response. Accordingly, IL-6 secretion was increased following PU-H71 and radiotherapy co-treatment ex vivo. Levels of angiogenic and inflammatory factors such as MIP-2, SDF-1, and VEGF were increased under in vitro conditions but not under ex vivo conditions. These results demonstrated for the first time that PU-H71 enhances therapeutic effects of radiotherapy especially in highly metastatic breast carcinoma but a possible increase in inflammatory response should also be considered.

Stage I small cell carcinoma of the endometrium: survival and management options.

Small cell carcinoma (SCC) of the endometrium is a rare but aggressive disease with early systemic involvement. Patient survival is short. To date, no effective treatment protocol has been established. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. The case of a patient with stage IB endometrial SCC is presented with an overview based on all reported cases of SCC of the endometrium and its treatment with particular reference to stage I cases.

[Treatment modalities of nasopharyngeal angiofibroma]. / Nazofarenks anjiyofibromlarinda tedavi yaklasimlari.

Nasopharyngeal angiofibroma is a rare, benign vascular tumor originating from the sphenopalatine foramen. It primarily affects adolescent males. Due to its propensity to locally destructive growth, the tumor may lead to fatal epistaxis, intracranial extension, and life-threatening complications such as intraoperative hemorrhage. Many treatment modalities have been used for the management of nasopharyngeal angiofibroma, but surgery and external beam radiation therapy have proved to be the only effective treatment modalities with acceptable morbidity. While endoscopic surgery provides successful results for early stage tumors, recent technological advances in radiotherapy offer significant advantages in advanced and recurrent tumors.

TRAIL death receptor-4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

PURPOSE: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. METHODS AND MATERIALS: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. RESULTS: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. CONCLUSIONS: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

Endostatin and irradiation modifies the activity of ADAM10 and neprilysin in breast cancer cells.

Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain­containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells. 4T1 and 4THMpc cells were treated with recombinant murine ES (4 µg/ml) alone, RT (45 Gy) alone or with ES + RT. ADAM10 enzyme activity was determined using a tumor necrosis factor­α converting enzyme (α­secretase) activity assay kit, and NEP enzyme activity was measured with a fluorometric assay based on the generation of free dansyl­D­Ala­Gly from N-dansyl-Ala-Gly-D-nitro-Phe-Gly, the substrate of NEP. Western blotting analysis was performed to determine whether the altered enzyme activity levels of the two cell lines occurred due to changes in expression level. These data indicate that ES independently potentiates the activity of ADAM10 and NEP enzymes in 4T1 and 4THMpc breast cancer cells.

Thalidomide combined with irradiation alters the activity of two proteases.

The aim of the present study was to investigate the effects of thalidomide, a drug known for its anti­angiogenic and antitumor properties, at its cytotoxic dose previously determined as 40 µg/ml (according to four cytotoxic test results). The effect of the drug alone and in combination with radiotherapy using Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance­P degrading A disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post­capsaicin (4THMpc). Thalidomide (40 µg/ml) exerted differing effects on the activities of ADAM10 and NEP enzymes. In 4T1 cells, 40 µg/ml thalidomide alone did not alter ADAM10 enzyme activity. 60Co irradiation at 45 Gy alone caused a 42% inhibition in ADAM10 activity, however, the inhibition increased to 89% when combined therapy was used. By contrast, in the 4THMpc cell line, 40 µg/ml thalidomide alone induced a 66.6% increase in ADAM10 enzyme activity. Radiotherapy alone and thalidomide with 60Co combined therapy caused a 33.3 and 40% inhibition of ADAM10 activity, respectively. In 4T1 cells, thalidomide alone caused a 40.9% increase in NEP activity. Radiation therapy alone or in combination with the drug caused a 40.7% increase in NEP activity. In more aggressive 4THMpc cells, thalidomide alone caused a 26.6% increase in NEP activity. Radiotherapy alone and combined therapy caused a 33.3 and 37% increase in enzyme activity, respectively. To the best of our knowledge, the present study is the first to demonstrate that thalidomide alone or in combination with radiotherapy exhibits significant cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell lines indicating that this drug affects the enzymatic activity of ADAM10 and NEP in vitro.

Clinical prognostic factors of adjuvant radiation therapy for low-grade gliomas: results of 10 years survival.

OBJECTIVE: Low-grade gliomas compose 5-20% of all glial tumors. The prognosis of the disease can be anticipated by specific clinical factors determined during diagnosis. For this purpose, our study investigated the clinical prognostic factors for low-grade gliomas. METHODS: Patients diagnosed with histopathologically confirmed low-grade glioma, followed by Akdeniz University and Süleyman Demirel University School of Medicine, Department of Radiation Oncology between 1999 and 2013 were included in the study. The examination of survival by single variable analyses were performed by log rank test. For the multivariate analysis, independent factors for the prediction of survival by using possible factors determined by previous analyses were examined by using Cox regression analysis. RESULTS: Fifty-five patients were included in the study. The mean follow-up period was determined as 60 ± 57 (4.5-168.1) months. Five-year overall survival was determined as 69% and 10-year overall survival was determined as 40%. When the potential prognostic factors were studied in Cox regression model, pre-radiotherapy age below 40 and gross-total excision were determined as good prognostic factors. CONCLUSION: We demonstrated that the aggressive surgical resection provided a better survival advantage both in single variable analyses and multivariate analyses. Consequently, although the low number of patients was the most important limitation in our study, we consider that patient age and extent of resection are the most important clinical prognostic factors in low-grade gliomas.

Endostatin enhances radioresponse in breast cancer cells via alteration of substance P levels.

Radiotherapy is widely used in the treatment of cancer. On the other hand, endostatin is considered to be a potent inhibitor of angiogenesis. Therefore, to test whether ES combined with RT overcomes the limitations of each monotherapy the present study investigated the effects of endostatin (ES), radiotherapy (RT) or combination therapy on the growth of mouse breast cancer cells as well as on the expression of substance P in vitro. The breast cancer cell lines 4T1 and 4THMpc were treated with recombinant murine ES (0.5, 1, 2, 4 and 8 µg/ml) alone, RT (45 Gy) alone or as a combination therapy. Cell proliferation was evaluated using an MTS assay and the results were verified by the Live/Dead assay. Immunoprecipitation and Western blotting analysis were performed to determine whether the substance P levels of the two cell lines occurred due to substance P content. Results showed that ES alone resulted in a low but significant inhibition in the growth of 4T1 and 4THMpc cell lines (27.63 and 21.75%, respectively). RT alone inhibited the growth of 4T1 (30.81%) and 4THMpc (39.64%) cells. A combination of ES with RT enhanced growth inhibition in the cells (83% in 4T1 and 80% in 4THMpc). The amount of substance P, both in the conditioned media and the cell lysates, increased within 72 h after RT. This increase was inhibited when ES and RT were applied in combination. These data indicate that ES inhibits the in vitro growth of breast cancer cells and potentiates the anti-tumor effects of RT at appropriate doses via alteration of the amount of substance P and thus an increase of radioresponse.