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WOS: 000466983900003, PubMed ID: 29694664, AIM: To systematically investigate the role of artificial small interfering RNA (SiRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. MATERIAL and METHODS: Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and "glioblastoma," either individually or combined ("OR" and "AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). RESULTS: After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. CONCLUSION: To be able to evaluate the clinical use of siRNAs, there is an urgent need for in vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

WOS: 000407701900010, PubMed ID: 28641566, Purpose: The present study aimed to analyze the researches that are at the experimental phase concerning osteosarcoma treatment. The researches included drug delivery systems which allow controlled release and imbue small interfering-/micro-ribonucleic acid. Methods: Without any language preference, we searched US National Library of Medicine National Institutes of Health, Embase, OVID, Cochrane Library database of clinical trials from 1843 to May 25, 2016 and traced all the references of incorporated documents. The data were evaluated using descriptive statistics and the results are shown as frequency (%). Results: We haven't encountered any drug delivery system in which Small interfering ribonucleic acid/ micro ribonucleic acid oligonucleotides were embedded successfully against osteosarcoma. There has been only one research in which hairpin-ribonucleic acid was embedded. Conclusion: It was considered that drug delivery system enabling controlled oligonucleotide release in the treatment period of osteosarcoma was not projected for the clinical use. However, it cannot be neglected that the mentioned experimental studies with regard to osteosarcoma treatment establish the basis of target therapies. The method in question looks promising regarding effective treatment of osteosarcoma in the future.

Introduction: The aim of this study was to compare computed tomography (CT)- and positron emission tomography (PET)/CT-based gross tumor volume (GTV) delineation and its subsequent expansion to the planning target volume (PTV), and to analyze the resultant doses of 3-dimensional conformal radiotherapy (3D-CRT) to critical organs. Methods: 15 patients with unresectable extrahepatic cholangiocarcinoma (EHCC) were enrolled into this study. PTVCT-based plans were initially made, and then PTVPET-CT-based plans were created using the same beam angles and isocenter. The dosimetric parameters analyzed included GTVCT, PTVCT, GTVPET-CT and PTVPET-CT. Prescribed and delivered radiation doses to target volumes and delineated organs at risk were also compared. Results: Mean GTV and PTV were significantly reduced in the PET/CT-based plan compared to the CT-based plan; the mean reductions of GTV and PTV were 28.7% and 15.2%, respectively. The mean value for GTVPET/GTVCT mismatch was 49.5 ± 28.9%, and that for GTVCT/GTVPET was 95.9 ± 19.5%. The mean value for PTVPET-CT/PTVCT mismatch was 21.9 ± 7.0% and that for PTVCT/PTVPET-CT was 39.1 ± 9.2%. Liver doses were significantly reduced (17.1%) in the PET/CT-based plan compared to the CT-based plan; the doses received by at least 30% and 50% of the liver were 30.0%, and 27.3%, respectively. Conclusion: The potential benefit of PET/CT is the reduction in geographic misses and regional treatment failures associated with CT-based planning.

WOS: 000384723200003 PubMed ID: 27194356 This is a literature review of studies focusing on the preparation of hydrogels for use as oncological drug delivery systems in the treatment of osteosarcoma (OS). The databases of the US National Library of Medicine National Institutes of Health, Embase, OVID, and Cochrane Library, and the references of retrieved studies, were traced from 1843 to December 21, 2015, without language restrictions. The obtained data were evaluated by complementary statistical methods. Potentially relevant studies were found and included in the analysis. OS-specific chemotherapeutic agents can be successfully embedded within the hydrogels and these drug-loaded hydrogels can be applied locally, rather than systemically, without organ tissue toxicity. Further, OS-specific drug-loaded hydrogels significantly increased tumor inhibition and decreased osteolysis and lung metastases. Drug-loaded hydrogels could be useful in the treatment of OS, although their development remains at the experimental phase. Following evaluation of their application in surgery and the completion of drug release kinetics studies, drug-loaded hydrogels could be tested on living mammals in large samples with the aim of applying these in clinical settings. In the future, development of such drug delivery systems and application of targeted approaches against osteosarcoma and other malignancies may render surgery, radiotherapy and chemotherapy unnecessary.

Cell culture and primary cell cultures have been widely used in research in many fields of medicine, particularly cancer research. With the help of cell culture studies, the underlying molecular mechanisms and effects of pharmacological agents have been determined to a great extent. The tumor tissue used for osteosarcoma primary cell culture was obtained from resection surgery carried out in cases with proximal fibula fibroblastic osteosarcoma after three multiagent (neoadjuvant) chemotherapy treatments. The present study not only describes how to prepare human primary osteosarcoma (OS) cell cultures but also encourages and guides orthopedic surgeons in how to set up an in vitro experiment for a drug research.

BACKGROUND To evaluate pathologically confirmed incidence of pseudoprogression and its impact on survival in glioblastoma multiforme (GBM) patients treated with radiotherapy and concurrent temozolomide (TMZ), followed by 6 months of TMZ maintenance therapy. MATERIALS AND METHODS Sixty-three patients with histologic proof of GBM underwent 60 Gy (2 Gy/fr, 30 fractions) of brain radiotherapy concurrent with continuous 75 mg/m/d TMZ, followed by 6 cycles of maintenance TMZ (200 mg/m/d for 5 d, every 28 d). Response assessment was performed by magnetic resonance imaging every 2 months. All patients with radiologic doubt of early tumor progression (≤6 mo) underwent salvage surgery. RESULTS All patients underwent surgical resection. Gross total, subtotal resection, and biopsy were performed in 17 (27.0%), 32 (51.6%), and 14 (21.4%) patients, respectively. Lesion enlargement on first follow-up magnetic resonance imaging evidenced in 28 (44.4%) patients. Salvage pathologies revealed pseudoprogression in 12 of 28 (42.8%) patients corresponding to an overall pseudoprogression rate of 19%. Survival analysis revealed that patients with pseudoprogression had superior overall and progression-free survival rates at both 1 and 2 years (P

Sarcomatoid carcinoma is a rare tumor of the urinary bladder accounting for less than 0.5% of all primary urinary bladder tumors. Since the patients were presented with large tumor with extended stages, outcome was found to be poor. In order to improve local control, adjuvant local treatment may be practical. We report a rare case with sarcomatoid carcinoma of the urinary bladder diagnosed with immunuhistochemical (IHC) study and treated with 3D-conformal radiotherapy (3DCRT) post-operatively. A 55-year old female patient complained about painless hematuria for 2 months. Computed tomography of the pelvic region revealed tumor and wall thickening at the left posterolateral side of the bladder. Total cystectomy with lymph node dissection and total abdominal hysterectomy and bilateral salphingo-oopherectomy was performed and histopathological and immunohistochemical findings strongly correlate with sarcomatoid carcinoma. The patient was treated with 3D conformal radiotherapy (3DCRT) with a total dose of 59.4 Gy with 1.8 Gy fractional daily doses. Patient was alive without any local recurrence and distant metastasis 10 months after surgery.

Background In this retrospective study, we investigated potential impact of weight change according to oral glutamine supplementation (GLT) on survival in patients with stage IIIB non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. Materials and methods Of the 142 patient evaluated retrospectively, 84 received GLT (GLT+), and 58 refused GLT intake (GLT-) and analyzed as control group. GLT was given at a daily dose of 30 g in powder form mixed with fruit juices. All patients received thoracic radiotherapy (TRT) to a total dose of 60-66 Gy (2Gy/Fx) concurrently with 2 cycles of cisplatin-based chemotherapy. Results During CRT, 76 (53.5) cases lost weight while remaining cases retained or gained weight. Weight loss in GLT- group (74.1%) was more frequent than GLT+ group (39.3%) (p Table 1 ) revealed cases in GLT+ group that retained or gained weight had the best outcome compared to the others. Bonferoni correction of two groups that retained of gained weight (p must be Table: 1620 Survival results according to glutamine supplementation (GLT) and wieght loss (WL) GLT- and KK+ GLT- and KK- GLT+ and KK+ GLT+ and KK- P-value Median OS Months) (95%CI) 15.7 (11.8-19.6) 21,7 (12.1-31.3) 13.5 (9.8-17.2) Not reached yet 1-year OS 65.1 93.3 60.6 98.0 2-year OS 12.1 44.9 3.8 58.3 Conclusion Results of this study demonstrated that GLT supplementation during CRT could prevent weight loss, yielding a better survival outcome in locally advanced NSCLC. Moreover, weight loss indicates poor prognosis irrespective of GLT use, and no long term survivors in GLT- group with weight loss suggests GLT resistance as a potentially poor prognostic factor, which warrants to be verified by further studies with larger cohorts. Disclosure All authors have declared no conflicts of interest.

Background Vitamin D is a growth factor improving bone mineralization, and regulating osteoblastic activity and longitudinal bone growth. In this study, impact of vitamin D supplementation administered prior to fractionated radiotherapy (RT) in reducing RT-induced epiphyseal injury is investigated. Materials and methods Six week old male Sprague-Dawley rats were enrolled to one of the four groups: Group 1 was assigned as control group (n = 7); Group 2 received fractionated RT alone; Group 3 received 50000 IU/kg i.m. vitamin D3 injection alone; and Group 4 received 50000 IU/kg i.m. vitamin D3 injection prior to fractionated RT. Fractionated RT in the irradiated groups was delivered to distal femur and proximal tibia in the left legs of each rats to a total dose of 24 Gy in 3 fractions with the contralateral right leg as the non-irradiated control. Vitamin D3 injection in Group 3 was performed on the day before the RT. Bone growth was calculated according to the lengths of femur, tibia and total leg measured on the radiographs taken at the time and 6 weeks after the delivery of RT. Results RT resulted in a mean percent overall limb growth loss of 56.2 ± 6.7 and a mean percent overall limb discrepancy of 12.7 ± 1.3. Administration of 50000 IU/kg i.m. vitamin D3 before RT reduced the mean percent overall limb growth loss and the mean percent overall limb discrepancy to 28.5 ± 5.6 and 4.4 ± 3.3, respectively. These values were significantly different compared with the groups receiving irradiation alone (P = 0.001 for each). Conclusion These results demonstrates the potential for vitamin D3 administered before fractionated RT to significantly reduce the RT-induced epiphyseal injury. Disclosure All authors have declared no conflicts of interest.

Background Chromosomal rearrangements in the receptor tyrosine kinase (RTK) ROS1 define a new molecular subset of NSCLC. ALK inhibitors can inhibit ROS1 kinase activity in cell lines. We examined the efficacy and safety of crizotinib, a small molecule inhibitor of two other RTKs, MET and ALK, in patients with advanced, ROS1-rearranged NSCLC. Methods Patients with advanced NSCLC harboring ROS1 rearrangement, as determined using a break-apart FISH assay, were recruited into an expansion cohort of the original phase 1 study of crizotinib. Patients were treated with crizotinib at the standard oral dose of 250 mg BID. The objective response rate (ORR) was determined based on RECIST v1.0. The disease control rate (DCR; stable disease [SD] + partial response [PR] + complete response [CR]) was evaluated at weeks 8 and 16. Results At the time of data cut-off on April 19, 2012, 15 patients with ROS1 NSCLC had received crizotinib and 14 were evaluable for response. The median age was 54 years (range 31–72). Fourteen patients were never-smokers and all had adenocarcinoma histology. All patients were confirmed negative for ALK rearrangement. The median number of prior treatments was 1 (range 0–6). The first ROS1 patient received crizotinib on October 19, 2010. To date, the ORR is 57% (8/14; 95% CI 28.9–82.3), with 7 PR and 1 CR. There were 4 SD, one of which was unconfirmed as PR at the time of data cut-off. The DCR at 8 weeks was 79% (11/14). Median duration of treatment was 25.7 weeks (range 0.1 + to 65.3 + ), and 12 patients continue on study. The pharmacokinetics, antitumor activity and safety profile of crizotinib in this group of patients were similar to those observed in patients with ALK-positive NSCLC. Conclusions Crizotinib is associated with clinically significant antitumor activity in patients with ROS1 NSCLC. Similar to ALK, ROS1 rearrangement defines another unique molecular subset of NSCLC patients for whom crizotinib therapy may be highly effective. Importantly, this study represents the first clinical investigation of ROS1 as a driver mutation and therapeutic target in cancer. Disclosure S.I. Ou: Advisory role: Pfizer, Genentech. Compensated Honoraria: Pfizer, Genentech, Lilly. Myself Research funding: Pfizer. Myself (institution). D.R. Camidge: Advisory role: Pfizer. Myself. Honoraria: Pfizer. Myself. L. Tye: Employment: Pfizer. Clinician. Myself. Stock Ownership; Pfizer. Myself. K. Wilner: Emplyement: Pfizer. Senior Director. Myself. Compensated. Stock ownership: Pfizer. Myself. M. Varella-Garcia: Honoraria: Abbott Molecular. Myself. funding for the trial provided by NIH - yes. A.T. Shaw: Advisory role: Pfizer, Ariad, Chugai, Novartis, Daiichi-sankyo. Myself. Compensated Research funding: Astra Zeneca, Novartis. Myself. All other authors have declared no conflicts of interest.

Background Aim of the study was to retrospectively assess the feasibility of radical chemoradiotherapy in terms of tolerability and survival outcomes in medically fit 71 to 79 years old stage IIIB NSCLC patients. Materials and methods From the hospital records, 78 medically fit, septuagenerians with stage IIIB lung carcinoma were evaluated. Patients should have performance of ECOG 0-1, body mass index of ≥20kg/m2, and weight loss of Results Patients characteristics are given in Table 1 . All patients received planned 66 Gy TRT but 55 of them (70.5%) could receive 2 cycles of chemotherapy. In general, treatment was well-tolerated with no grade 4/5 acute toxicity. Late term toxicity was reported in 3 (3.8%); esophagitis in 3 and peripheral neuropathy in 1 patient. At a median follow up of 19.3 months (4.4-39.8), 19 patients (24.4%) were alive, 8 of whom (10.3%) were with no disease progression. Median overall, local-regional progression-free and progression-free survival were 17.5 (95%CI: 15.2-19.8), 10.1 (95% CI: 7.8-12.4) and 7.3 months (95% CI: 5.9-8.9). On univariate analyses, histology (p = 0.017), Nodal status (p = 0.011), number of concomitant CT (p Age Median 74.4 (71 – 79) Sex Male Female 51 (65.4) 27 (34.6) Performance status ECOG 0 ECOG 1 38 (48.7) 40 (51.3) Histology SCC Adeno 43 (55.1) 35 (44.9) Stage T2N3 T3N3 T4N2 T4N3 15 (19.2) 22 (28.2) 28 (35.9) 13 (16.7) Conclusion Results present here suggests that CRT in highly selected medically fit septuagenarians with LA-NSCLC yields survival outcomes improved up to that achieved in younger patients, with a relatively acceptable toxicity profile. Table 1 Disclosure All authors have declared no conflicts of interest.

Background Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. Methods The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. Results Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. Conclusion In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.