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Randomized Trial of Monthly Versus As-Needed Intravitreal Ranibizumab for Radiation Retinopathy-Related Macular Edema: 1-Year Outcomes.
Schefler, AC, Fuller, D, Anand, R, Fuller, T, Moore, C, Munoz, J, Kim, RS, ,
American journal of ophthalmology. 2020;:165-173
Abstract
PURPOSE To assess efficacy of intravitreal ranibizumab injections and targeted panretinal photocoagulation (TRP) for radiation retinopathy-related macular edema. DESIGN Phase IIb, prospective, randomized clinical trial. METHODS Setting: Multicenter. SUBJECTS Forty eyes in 40 treatment-naïve patients with radiation-induced macular edema and a resulting decrease in visual acuity ranging between 20/25 and 20/400 (Snellen equivalent). INTERVENTION Patients either received intravitreal 0.5 mg ranibizumab monthly, monthly ranibizumab with TRP, or 3 monthly ranibizumab (loading doses) followed by as-needed (PRN) injections and TRP. After week 52, all subjects entered a treat-and-extend protocol for ranibizumab. MainOutcomeMeasures: Mean Early Treatment Diabetic Maculopathy Study (ETDRS) BCVA change from baseline. RESULTS Mean patient age was 57 years (range, 22-80 years), ETDRS BCVA was 56.7 letters (20/74 Snellen equivalent), and central macular thickness (CMT) was 423 μm (range, 183-826 μm). Thirty-seven patients completed the month 12 visit (92.5%), at which time the change in mean BCVA was +4.0 letters, -1.9 letters, and +0.9 letters in the monthly, monthly plus laser, and PRN plus laser cohorts, respectively. There was a significant difference in mean BCVA at 1 year among all 3 cohorts (P < .001), as well as between cohorts in pairwise comparisons, with the most significant gains in the monthly group. A total of 82.5% of the patients retained visual acuity of 20/200 or better, and 20.0% improved 10 or more ETDRS letters. CONCLUSIONS Ranibizumab may improve vision and anatomy in patients with radiation retinopathy-related macular edema and prevent vision loss through 48 weeks of therapy. Monthly injections were more effective than as-needed approach, and the addition of TRP yielded no therapeutic benefits.
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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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Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.
Soran, A, Ozmen, V, Ozbas, S, Karanlik, H, Muslumanoglu, M, Igci, A, Canturk, Z, Utkan, Z, Ozaslan, C, Evrensel, T, et al
Annals of surgical oncology. 2018;(11):3141-3149
Abstract
BACKGROUND The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.
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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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Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP).
Klement, RJ, Sweeney, RA
Clinical nutrition ESPEN. 2016;:e1-e6
Abstract
BACKGROUND We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. METHODS All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m2 and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index <70, pregnancy, metallic body parts that interfere with bioimpedance analysis (BIA), type I diabetes, known enzyme defects that contradict a KD and renal insufficiency. Randomization is achieved by all consecutive patients first entering the control group and then an intervention group 1 until both groups contain 15 breast, 15 colorectal and 5 head and neck cancer patients. Intervention group 1 will receive each radiotherapy fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) 50-250 ml of a medium-chain triglyceride drink (betaquick®, vitaflo, Bad Homburg, Germany) plus (ii) 5-15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. ENDPOINTS Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas.
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Nutritional Supplement Based on Zinc, Prebiotics, Probiotics and Vitamins to Prevent Radiation-related Gastrointestinal Disorders.
Scartoni, D, Desideri, I, Giacomelli, I, Di Cataldo, V, Di Brina, L, Mancuso, A, Furfaro, I, Bonomo, P, Simontacchi, G, Livi, L
Anticancer research. 2015;(10):5687-92
Abstract
AIM: The present phase II study aimed to evaluate the tolerance and safety of Dixentil, a nutritional supplement based on zinc with the addition of prebiotics (galacto-oligosaccharides), tyndalized probiotics (Lactobacillus acidophilus and L. casei) and vitamins B1, B2 and B6, and nicotinamide), given as prophylaxis to patients undergoing pelvic radiotherapy and its efficacy in the prevention and reduction of radiation-related gastrointestinal disorders. PATIENTS AND METHODS Forty consecutive patients who were candidates for pelvic radiotherapy received Dixentil before starting and during radiotherapy. The primary end-point was to evaluate the safety and tolerance of Dixentil. Secondary end-points were incidence and severity of radiation-induced diarrhea and number of patients who discontinued radiotherapy because of diarrhea. RESULTS Radiation-induced enteritis occurred in 17 patients, grade I and grade II diarrhea was documented in 14 and 3 patients respectively; no grade III or IV diarrhea was observed. Radiotherapy was discontinued due to treatment-induced enteritis only in two patients for 6 days. CONCLUSION Use of Dixentil is an easy, safe, and feasible approach to protect patients against the risk of radiation-induced diarrhea.
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A hyaluronic acid-based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo.
Cirillo, N, Vicidomini, A, McCullough, M, Gambardella, A, Hassona, Y, Prime, SS, Colella, G
Journal of cellular physiology. 2015;(7):1421-9
Abstract
Virtually all patients receiving radio- and chemotherapy for cancer develop oral mucositis, a severe and highly debilitating condition. The onset of mucositis is thought to involve the production of reactive oxygen species (ROS) in the submucosa. Here we investigated a possible protective effect of a commercial formulation of hyaluronic acid (HA) enriched with amino acids (Mucosamin(®)) against the damage induced by oxidative stress both in vitro and in vivo. Transient exposure of normal human oral fibroblasts to hydrogen peroxide (H(2)O(2)) led to irreversible senescence, as demonstrated by sustained increase in the levels of p16(INK4A) and SA-βGal. Conditioned media from senescent fibroblasts induced detrimental effects on keratinocytes, as shown by reduced metabolic activity and migration capability. Pre-treatment with Mucosamin(®) prevented H(2)O(2) -induced, but not TGF-β-induced, fibroblast senescence with a concomitant reduction of fibroblast-induced loss of keratinocyte vitality and functional activity. Finally, data from a case-series of patients undergoing radio/chemotherapy strongly suggested that prophylactic use of the hyaluronic acid-based compound in the form of a spray may be effective in preventing the onset of oral mucositis.
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Radiotherapy alone versus radiochemotherapy in patients with stage IIIA adenocarcinoma (ADC) of the lung.
Jeremić, B, Miličić, B, Milisavljević, S
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2013;(9):747-53
Abstract
PURPOSE To evaluate the outcome of radiotherapy (RT) versus radiochemotherapy (RT-CHT) in patients with locally advanced (stage III) inoperable adenocarcinoma of the lung. PATIENTS AND METHODS 146 patients with these characteristics were among 600 patients enrolled into five prospective trials and were treated with either hyperfractionated (Hfx) RT (64.8 and 69.6 Gy using 1.2 Gy bid) alone (n = 33) or with Hfx RT (64.8 and 69.6 Gy using 1.2 Gy bid and 67.6 Gy using 1.3 Gy bid) and concurrent carboplatin-etoposide or paclitaxel-carboplatin (n = 113). RESULTS The median times and 5-year overall survival (OS), local progression-free survival (LPFS) and the distant metastasis-free survival (DMFS) rates for all 146 patients were 17, 20 and 20 months, respectively, and 15, 26 and 33, respectively. RT-CHT was superior to RT alone in terms of both OS (MST 19 vs. 12 months, respectively, 5-year OS 18 vs. 6 %, respectively; p = 0.003) and LPFS (MTLP 21 vs. 15 months, respectively, 5-year LPFS 28 vs. 0 %; p = 0.06), but not the DMFS (p = 0.43). In all 146 patients, the most frequent acute high-grade toxicity was esophageal, bronchopulmonary and hematological (each 12 %), while the most frequent late high-grade toxicity was bronchopulmonary (4 %) and esophageal (3 %). RT-CHT caused significantly more frequent acute high-grade (>3) esophageal (15 %), and hematological (15 %), while late high-grade toxicity was similar between RT and RT-CHT groups of patients. CONCLUSION RT-CHT achieved excellent results (MST 19 months, 5-year survival 18 %) in this patient population accompanied with low toxicity, comparing favorably to results of other similar studies.