Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

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 â€Å“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.

Is it Possible to Treat Osteosarcoma Using Oligonucleotides Confined into Controlled Release Drug Delivery Systems?

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.

Systematic Evaluation of Drug-Loaded Hydrogels for Application in Osteosarcoma Treatment.

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.

Comparison of computed tomography- and positron emission tomography-based radiotherapy planning in cholangiocarcinoma.

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.

Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: retrospective analysis of 89 patients.

We retrospectively evaluated the toxicity and efficacy of concurrent radiochemotherapy (C-RCT) in medically fit septuagenarians with stage IIIB non-small cell lung carcinoma (NSCLC). Eighty-nine medically fit, stage IIIB NSCLC septuagenarians were included. Thoracic radiotherapy to a total dose of 66 Gy in 2 Gy fractions was delivered concurrently with 1-2 cycles of cisplatin-based doublet chemotherapy. Treatment was relatively well-tolerated with no grade 4/5 acute toxicity. Acute grade 3 hematologic and non-hematologic toxicity rates were 55.1 and 39.3%, respectively. Late toxicity was reported in 3 (3.4%) patients: esophagitis (N = 2) and peripheral neuropathy (N = 1). At median 21.7 months (4.4-42.1), 26 patients (29.2%) were alive. Median overall, local-regional progression-free and progression-free survivals were 17.7, 10.5 and 7.8 months, respectively. On univariate analyses, histology (p < 0.03), nodal status (p = 0.038), number of concomitant chemotherapy (p < 0.001), and weight change during C-RCT (p < 0.001) demonstrated significant association with overall survival; while only number of chemotherapy and weight change (p < 0.001 for each) could retain their significance on multivariate analyses. Current results suggested that C-RCT in highly selected medically fit septuagenarians with LA-NSCLC may improve survival outcomes up to that achieved in younger patients, with a relatively acceptable toxicity profile.

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer.

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.

Pseudoprogression in patients with glioblastoma multiforme after concurrent radiotherapy and temozolomide.

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<0.05 for each, respectively). CONCLUSIONS: Current results indicates the urgency of need for novel imaging techniques and/or biochemical marker(s) that can better distinguish pseudoprogression from true progression to avoid unnecessary and potentially harmful surgical interventions in almost half of the radiologically progressive GBM patients. Our additional observation which suggests better survival for patients with pseudoprogression warrants to be studied in larger patient cohorts.

Sarcomatoid carcinoma of the urinary bladder treated with adjuvant radiotherapy: a case report.

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.