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Effect of probiotic bacteria on oral Candida in head- and neck-radiotherapy patients: A randomized clinical trial.
Doppalapudi, R, Vundavalli, S, Prabhat, MP
Journal of cancer research and therapeutics. 2020;(3):470-477
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Abstract
OBJECTIVE The aim of the study is to assess the effect of probiotic bacteria on oral Candida counts in cancer patients who are undergoing head- and neck-radiotherapy in a tertiary care center. STUDY DESIGN The study was a randomized clinical trial including 90 patients who just completed head- and neck-radiotherapy. MATERIALS AND METHODS Participants were randomly allocated into three equal sized groups, i.e., probiotics group, candid group, and combination groups. Oral rinse samples of the patients were collected before and after the intervention for the identification of Candida. The samples were incubated on Sabouraud's Dextrose Agar with Chloramphenicol at 37°C for 48 h, to assess the counts of colony-forming units/milliliter (CFU/ml) of Candida in saliva, and further on chrome agar plates to identify the Candida spp. Data were analyzed using mixed ANOVA to compare mean CFU/ml of Candida among three groups before and after the intervention. RESULTS A total of 86 patients were included in the final analysis and there was a statistically significant reduction in mean Candida spp. Counts (CFU/ml) after intervention in all the three groups (P = 0.000) and significant reductions identified in both probiotic and combination therapy groups. Apart from reduction in Candida albicans, significant decrease in Candida glabrata and Candida tropicalis was observed after probiotics usage compared to other groups. CONCLUSIONS The present study suggests that probiotic bacteria were effective in reducing oral Candida spp which can be recommended alone or in combination with traditional antifungal agents for effective reduction in oral Candida in head- and neck-radiotherapy patients.
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Cost-effectiveness analysis of long-course oxaliplatin and bolus of fluorouracil based preoperative chemoradiotherapy vs. 5x5Gy radiation plus FOLFOX4 for locally advanced resectable rectal cancer.
Wang, S, Wen, F, Zhang, P, Wang, X, Li, Q
Radiation oncology (London, England). 2019;(1):113
Abstract
PURPOSE To evaluate the cost-effectiveness of preoperative short-course radiotherapy (SCRT, 5 × 5 Gy) plus FOLFOX4 versus long-course oxaliplatin and bolus of fluorouracil based preoperative long-course chemoradiotherapy (LCCRT, 50.4 Gy in 28 fractions) in the management of cT4 or advanced cT3 rectal cancer (RC), both of which have been reported to achieve similar clinical effect in the NCT00833131 trial. MATERIALS AND METHODS A Markov decision-analytic model compared SCRT plus chemotherapy and LCCRT, by simulating three health states (disease-free survival (DFS), progressive disease (PD) and death). The primary outcomes were quality-adjusted life months (QALMs), costs, and incremental cost-effectiveness ratios (ICERs). Transition probabilities were based on the NCT00833131 trial. The costs were calculated from a Chinese payers' perspective. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $2370.47 (3 × GDP) per QALM gained. Sensitivity analysis was performed to model uncertainty in these parameters. RESULTS The overall costs for SCRT plus chemotherapy and LCCRT were $78,937 and $38,140 with effectiveness of 29.92 QALMs and 22.99 QALMs, respectively. SCRT plus chemotherapy increased costs and QALM by $40,797.34 and 6.93 compared to LCCRT, resulting in an ICER of $5884.56/QALM gained. In the DFS state, the whole cost for SCRT plus chemotherapy and LCCRT were $11,490.03 and $10,794.06 with an effectiveness of 21.70 QALMs and 19.65 QALMs, respectively. SCRT plus chemotherapy increased cost and QALM by $695.97 and 2.05 compared to LCCRT, resulting in a ICER of $339.50/QALM gained, which below the WTP. The utility associated with the DFS state was the most influential factor on the cost-effectiveness of SCRT plus chemotherapy. When the cost of PD state below $1920, the ICER of SCRT compared with LCCRT below the WTP. CONCLUSION Compared with LCCRT, SCRT plus chemotherapy is a more cost-effective strategy for locally advanced resectable RC in the DFS state as well as in the all states when the cost of PD state below $1920.
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Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.
Dietz, A, Wichmann, G, Kuhnt, T, Pfreundner, L, Hagen, R, Scheich, M, Kölbl, O, Hautmann, MG, Strutz, J, Schreiber, F, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2018;(10):2105-2114
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BACKGROUND The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). PATIENTS AND METHODS Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. RESULTS Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. CONCLUSIONS Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. CLINICAL TRIAL INFORMATION NCT00508664.
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Safety and Efficacy of Botulinum Toxin to Preserve Gland Function after Radiotherapy in Patients with Head and Neck Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blinded Phase I Clinical Trial.
Teymoortash, A, Pfestroff, A, Wittig, A, Franke, N, Hoch, S, Harnisch, S, Schade-Brittinger, C, Hoeffken, H, Engenhart-Cabillic, R, Brugger, M, et al
PloS one. 2016;(3):e0151316
Abstract
This prospective, randomized, placebo-controlled, double-blinded phase I clinical trial investigates safety and efficacy of botulinum toxin (BoNT) to preserve gland function after radiotherapy in patients with head and neck cancer. Twelve patients with advanced head and neck cancer were injected with BoNT into the submandibular glands prior to primary radiochemotherapy. Six patients received BoNT/A and 6 patients BoNT/A and B, half of each subgroup into their left and the other half into their right gland. As an internal control, sodium chloride was injected into the respective contralateral gland (placebo). For the evaluation of the salivary gland function, technetium pertechnetate salivary gland scintigraphy was performed before and after the end of radiotherapy. BoNT/A and B were well tolerated. Analysis of the scintigraphic data revealed no statistically significant difference between BoNT and placebo regarding the scintigraphic uptake difference (pBoNT/A = 0.84 and pBoNT/A-B = 0.56 for BoNT/A vs. placebo and BoNT/A-B vs. placebo, respectively). We also found no significant difference in treatment between BoNT and placebo in terms of salivary excretion fraction (pBoNT/A = 0.44; pBoNT/A-B = 0.44). This study demonstrates that BoNT can be safely combined with radiochemotherapy. Dosing and timing of BoNT injection should be further investigated for efficacy analysis. Trial Registration German Registry for Clinical Trails DRKS00004595.
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External beam radiotherapy for head and neck cancers is associated with increased variability in retinal vascular oxygenation.
Higginson, DS, Sahgal, A, Lawrence, MV, Moyer, S, Stefanescu, M, Willson, AK, Qaqish, B, Zanation, A, Marks, LB, Garg, S, et al
PloS one. 2013;(8):e69657
Abstract
BACKGROUND Radiation retinopathy is a possible post-treatment complication of radiation therapy. The pathophysiologic mechanism is hypothesized to be microvascular in origin, but evidence is limited. In an effort to study retinal oxygenation in these patients, we herein evaluate the repeatability and variability of retinal oximetry measurements in subjects who had previously received radiation and make comparisons to a cohort of unirradiated subjects. METHODS Using retinal oximetry, a non-invasive imaging modality, we performed in vivo measurements of arteriole (SaO2) and venule SO2 (SvO2) in subjects (n = 9, 18 retinas) who had received incidental radiation to their retinas (≥ 45 Gy to one retina) and in healthy subjects (n = 20, 40 retinas). A total of 1367 SO2 observations on 593 vessels in 29 persons were analyzed to assess three sources of variance in vessel SO2: 1) variance in repeated measurements of the same vessel ("repeatability"), 2) variance in different vessels within the same subject ("within-subject variability"), and 3) variance between subjects ("between-subject variability"). RESULTS Retinal oximetry measurements were highly repeatable in both irradiated patients and unirradiated subjects. The within-subject variability of SvO2 and SaO2 measurements constituted the highest component of variance in both groups and was significantly higher in venules vs. arterioles (relative effect size 1.8, p<0.001) and in irradiated subjects vs. unirradiated subjects (relative effect size 1.6, p<0.001). CONCLUSIONS Retinal oximetry is a highly repeatable technology and can be reliably used to study vascular oxygenation in irradiated subjects. Different vessels within the same subject exhibit a high degree of variability, suggesting that pooled analyses of multiple vessels are most likely to be informative of regional retinal oxygenation. Finally, irradiated subjects exhibited significantly higher within-subject variability in SO2 measurements, suggesting that radiation may cause regional alterations in retinal oxygen delivery and/or metabolism.
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Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option?
Kunikowska, J, Królicki, L, Hubalewska-Dydejczyk, A, Mikołajczak, R, Sowa-Staszczak, A, Pawlak, D
European journal of nuclear medicine and molecular imaging. 2011;(10):1788-97
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PURPOSE Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). A combination treatment using the high-energy 90Y beta emitter for larger lesions and the lower energy 177Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined 90Y/177Lu-DOTATATE therapy in comparison to 90Y-DOTATATE alone. METHODS Fifty patients with disseminated NET were included in the study prospectively and divided into two groups: group A (n=25) was treated with 90Y-DOTATATE, whereas group B (n=25) received the 1:1 90Y/177Lu-DOTATATE. The administered activity was based on 3.7 GBq/m2 body surface area in three to five cycles, with amino acid infusion for nephroprotection. RESULTS The median overall survival time in group A was 26.2 months while in group B median survival was not reached. Overall survival was significantly higher in group B (p=0.027). Median event-free survival time in group A was 21.4 months and in group B 29.4 months (p>0.1). At the 12-month follow-up, comparison of group A vs group B showed stable disease (SD) in 13 vs 16 patients, disease regression (RD) in 5 vs 3 patients and disease progression (PD) in 3 vs 4 patients; 4 and 2 patients died, respectively. The 24-month follow-up results were SD in nine vs ten patients, RD in one patient vs none and PD in four patients in both groups; three and four patients died, respectively. Side effects were rare and mild. CONCLUSION The results indicate that therapy with tandem radioisotopes (90Y/177Lu-DOTATATE) provides longer overall survival than with a single radioisotope (90Y-DOTATATE) and the safety of both methods is comparable.
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Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer.
Nourissat, A, Bairati, I, Samson, E, Fortin, A, Gélinas, M, Nabid, A, Brochet, F, Têtu, B, Meyer, F
Cancer. 2010;(9):2275-83
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BACKGROUND The purpose of the study was to identify predictors of weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer. METHODS This study was conducted as part of a phase 3 chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Their baseline characteristics, including lifestyle habits, diet, and quality of life, were assessed as potential predictors. Predictors were identified using multiple linear regressions. The reliability of the model was assessed by bootstrap resampling. A receiver operating characteristics curve was generated to estimate the model's accuracy in predicting critical weight loss (>or=5%). RESULTS The mean weight loss was 2.2 kg (standard deviation, 3.4). Five factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P<.001), higher pre-RT body weight (P<.001), stage II disease (P = .002), dysphagia and/or odynophagia before RT (P = .001), and a lower Karnofsky performance score (P = .028). There was no association with pre-RT lifestyle habits, diet, or quality of life. The bootstrapping method confirmed the reliability of this predictive model. The area under the curve was 71.3% (95% confidence interval, 65.8-76.9), which represents an acceptable ability of the model to predict critical weight loss. CONCLUSIONS These results could be useful to clinicians for screening patients with early stage HN cancer treated by RT who require special nutritional attention.
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Non-randomized therapy trial to determine the safety and efficacy of heavy ion radiotherapy in patients with non-resectable osteosarcoma.
Blattmann, C, Oertel, S, Schulz-Ertner, D, Rieken, S, Haufe, S, Ewerbeck, V, Unterberg, A, Karapanagiotou-Schenkel, I, Combs, SE, Nikoghosyan, A, et al
BMC cancer. 2010;:96
Abstract
BACKGROUND Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. For effective treatment, local control of the tumor is absolutely critical, because the chances of long term survival are <10% and might effectively approach zero if a complete surgical resection of the tumor is not possible. Up to date there is no curative treatment protocol for patients with non-resectable osteosarcomas, who are excluded from current osteosarcoma trials, e.g. EURAMOS1. Local photon radiotherapy has previously been used in small series and in an uncontrolled, highly individualized fashion, which, however, documented that high dose radiotherapy can, in principle, be used to achieve local control. Generally the radiation dose that is necessary for a curative approach can hardly be achieved with conventional photon radiotherapy in patients with non-resectable tumors that are usually located near radiosensitive critical organs such as the brain, the spine or the pelvis. In these cases particle Radiotherapy (proton therapy (PT)/heavy ion therapy (HIT) may offer a promising new alternative. Moreover, compared with photons, heavy ion beams provide a higher physical selectivity because of their finite depth coverage in tissue. They achieve a higher relative biological effectiveness. Phase I/II dose escalation studies of HIT in adults with non-resectable bone and soft tissue sarcomas have already shown favorable results. METHODS/DESIGN This is a monocenter, single-arm study for patients > or = 6 years of age with non-resectable osteosarcoma. Desired target dose is 60-66 Cobalt Gray Equivalent (Gy E) with 45 Gy PT (proton therapy) and a carbon ion boost of 15-21 GyE. Weekly fractionation of 5-6 x 3 Gy E is used. PT/HIT will be administered exclusively at the Ion Radiotherapy Center in Heidelberg. Furthermore, FDG-PET imaging characteristics of non-resectable osteosarcoma before and after PT/HIT will be investigated prospectively. Systemic disease before and after PT/HIT is targeted by standard chemotherapy protocols and is not part of this trial. DISCUSSION The primary objectives of this trial are the determination of feasibility and toxicity of HIT. Secondary objectives are tumor response, disease free survival and overall survival. The aim is to improve outcome for patients with non-resectable osteosarcoma. TRIAL REGISTRATION Registration number (ClinicalTrials.gov): NCT01005043.
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Cytokines levels, severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer--a prospective pilot study.
Meirovitz, A, Kuten, M, Billan, S, Abdah-Bortnyak, R, Sharon, A, Peretz, T, Sela, M, Schaffer, M, Barak, V
Radiation oncology (London, England). 2010;:16
Abstract
BACKGROUND The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy. PATIENTS AND METHODS Fifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-alpha) and anti-inflammatory (IL-10) cytokine levels before and during treatment. RESULTS A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube. CONCLUSION These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study.
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Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: the CINDERELLA trial.
Combs, SE, Burkholder, I, Edler, L, Rieken, S, Habermehl, D, Jäkel, O, Haberer, T, Haselmann, R, Unterberg, A, Wick, W, et al
BMC cancer. 2010;:533
Abstract
BACKGROUND Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. METHODS DESIGN In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy.Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival. DISCUSSION The Cinderella trial is the first study to evaluate carbon ion radiotherapy for recurrent gliomas, and to compare this treatment to photon FSRT in a randomized setting using an ion beam delivered by intensity modulated rasterscanning. TRIAL REGISTRATION NCT01166308.