scholarly journals Role of high-dose salvage radiotherapy for oligometastases of the localised abdominal/pelvic lymph nodes: A retrospective study

2019 ◽  
Author(s):  
Makoto Ito ◽  
Takeshi Kodaira ◽  
Yutaro Koide ◽  
Takahito Okuda ◽  
Shinichiro Mizumatsu ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Proportional Hazards Model ◽  
Primary Tumour ◽  
Cox Proportional Hazards Model ◽  
Salvage Radiotherapy ◽  
High Dose Group ◽  
High Dose ◽  
Significant Difference ◽  
Prescription Dose

Abstract Background: Abdominal/pelvic lymph node (LN) oligometastasis is a pattern of failure that is observed occasionally. Although radiotherapy may be useful for salvage therapy, the optimal prescription dose has not yet been clarified. This study assessed the efficacy of high-dose radiotherapy. Methods: Between 2008 and 2018, the medical records of 113 patients with 1–5 abdominal/pelvic LN oligometastases treated with definitive radiotherapy at 4 institutes were retrospectively analysed. The exclusion criteria were non-epithelial tumours, uncontrolled primary lesions, palliative intent, and re-irradiation. The prescription dose was evaluated by using the equivalent dose in 2 Gy fractions (EQD2); patients with EQD2 ≥60 Gy were the high-dose group. Kaplan-Meier analysis was used to evaluate the endpoints of overall survival (OS), local control (LC), and progression-free survival (PFS). Univariate log-rank and multivariate Cox proportional hazards model analyses were performed to clarify predictive factors for each endpoint. Toxicity rates were compared between the high-dose and low-dose groups. Results: The primary tumour sites included the colorectum (n = 28), uterine cervix (n = 27), endometrium (n = 15), and ovaries (n = 10). The 2-year OS, LC, and PFS rates were 63.1%, 59.7%, and 19.4%, respectively. On multivariate analyses, solitary oligometastasis, high-dose radiotherapy, and long disease-free interval were associated with significantly favourable OS (hazard ratio [HR]: 0.48, p = 0.02), LC (HR: 0.93, p < 0.001), and PFS (HR: 0.59, p = 0.01), respectively. Although high-dose radiotherapy did not significantly improve the 2-year OS of the entire cohort (74.8% vs. 52.7% in the high-dose vs. low-dose group; p = 0.08), it showed a significant difference on subgroup analysis for solitary oligometastasis (88.8% vs. 56.3%; p = 0.009). Late grade ≥3 toxicity included ileus in 7 cases (6%) and gastrointestinal bleeding in 4 (4%). There was no significant association between the irradiation dose and toxicity incidence. Conclusions: Salvage radiotherapy was feasible for oligometastasis of the abdominal/pelvic LNs. For solitary oligometastasis, the high-dose group showed favourable results considering LC and OS.

scholarly journals Role of high-dose salvage radiotherapy for oligometastases of the localised abdominal/pelvic lymph nodes: A retrospective study

2020 ◽  
Author(s):  
Makoto Ito ◽  
Takeshi Kodaira ◽  
Yutaro Koide ◽  
Takahito Okuda ◽  
Shinichiro Mizumatsu ◽  
...  
Keyword(s):  
Adverse Event ◽  
Salvage Therapy ◽  
Dose Group ◽  
Low Dose ◽  
Proportional Hazards Model ◽  
Primary Tumour ◽  
Cox Proportional Hazards Model ◽  
High Dose Group ◽  
High Dose ◽  
Prescription Dose

Abstract Background: Abdominal/pelvic lymph node (LN) oligometastasis, a pattern of treatment failure, is observed occasionally, and radiotherapy may work as salvage therapy. The optimal prescription dose, however, is yet to be determined. This study assessed the efficacy of high-dose radiotherapy. Methods: The medical records of 113 patients at 4 institutes were retrospectively analysed who had 1 to 5 abdominal/pelvic LN oligometastases and were treated with definitive radiotherapy between 2008 and 2018. The exclusion criteria included non-epithelial tumours, uncontrolled primary lesions, palliative intent, and re-irradiation. The prescription dose was evaluated by using the equivalent dose in 2 Gy fractions (EQD2). Patients receiving EQD2 ≥60 Gy were placed into the high-dose group, and the remaining others the low-dose group. Kaplan-Meier analyses were performed to evaluate overall survival (OS), local control (LC), and progression-free survival (PFS). Univariate log-rank and multivariate Cox proportional hazards model analyses were performed to explore predictive factors. Adverse events were compared between the high-dose and low-dose groups. Results: The primary tumour sites included the colorectum (n = 28), uterine cervix (n = 27), endometrium (n = 15), and ovaries (n = 10). The rate of 2-year OS was 63.1%, that of LC 59.7%, and that of PFS 19.4%. On multivariate analyses, OS were significantly associated with solitary oligometastasis (hazard ratio [HR]: 0.48, p = 0.02), LC with high-dose radiotherapy (HR: 0.93, p < 0.001), and PFS with long disease-free interval (HR: 0.59, p = 0.01). Whereas high-dose radiotherapy did not significantly improve 2-year OS in the entire cohort (74.8% in the high-dose vs. 52.7% in the low-dose; p = 0.08), it did in the subgroup of solitary oligometastasis (88.8% in the high-dose vs. 56.3% in the low-dose; p = 0.009). As for Late grade ≥3 adverse event, ileus was observed in 7 patients (6%) and gastrointestinal bleeding in 4 (4%). No significant association between the irradiation dose and adverse event incidence was found. Conclusions: As salvage therapy, high-dose radiotherapy was recommendable for oligometastasis in the abdominal/pelvic LNs. For solitary oligometastasis, LC and OS were significantly better in the high-dose group.

scholarly journals Role of high-dose salvage radiotherapy for oligometastases of the localised abdominal/pelvic lymph nodes: A retrospective study

2020 ◽  
Author(s):  
Makoto Ito ◽  
Takeshi Kodaira ◽  
Yutaro Koide ◽  
Takahito Okuda ◽  
Shinichiro Mizumatsu ◽  
...  
Keyword(s):  
Adverse Event ◽  
Salvage Therapy ◽  
Dose Group ◽  
Low Dose ◽  
Proportional Hazards Model ◽  
Primary Tumour ◽  
Cox Proportional Hazards Model ◽  
High Dose Group ◽  
High Dose ◽  
Prescription Dose

Abstract Background: Abdominal/pelvic lymph node (LN) oligometastasis, a pattern of treatment failure, is observed occasionally, and radiotherapy may work as salvage therapy. The optimal prescription dose, however, is yet to be determined. This study assessed the efficacy of high-dose radiotherapy.Methods: The medical records of 113 patients at 4 institutes were retrospectively analysed who had 1 to 5 abdominal/pelvic LN oligometastases and were treated with definitive radiotherapy between 2008 and 2018. The exclusion criteria included non-epithelial tumours, uncontrolled primary lesions, palliative intent, and re-irradiation. The prescription dose was evaluated by using the equivalent dose in 2 Gy fractions (EQD2). Patients receiving EQD2 ≥60 Gy were placed into the high-dose group, and the remaining others the low-dose group. Kaplan-Meier analyses were performed to evaluate overall survival (OS), local control (LC), and progression-free survival (PFS). Univariate log-rank and multivariate Cox proportional hazards model analyses were performed to explore predictive factors. Adverse events were compared between the high-dose and low-dose groups.Results: The primary tumour sites included the colorectum (n = 28), uterine cervix (n = 27), endometrium (n = 15), and ovaries (n = 10). The rate of 2-year OS was 63.1%, that of LC 59.7%, and that of PFS 19.4%. On multivariate analyses, OS were significantly associated with solitary oligometastasis (hazard ratio [HR]: 0.48, p = 0.02), LC with high-dose radiotherapy (HR: 0.93, p < 0.001), and PFS with long disease-free interval (HR: 0.59, p = 0.01). Whereas high-dose radiotherapy did not significantly improve 2-year OS in the entire cohort (74.8% in the high-dose vs. 52.7% in the low-dose; p = 0.08), it did in the subgroup of solitary oligometastasis (88.8% in the high-dose vs. 56.3% in the low-dose; p = 0.009). As for Late grade ≥3 adverse event, ileus was observed in 7 patients (6%) and gastrointestinal bleeding in 4 (4%). No significant association between the irradiation dose and adverse event incidence was found.Conclusions: As salvage therapy, high-dose radiotherapy was recommendable for oligometastasis in the abdominal/pelvic LNs. For solitary oligometastasis, LC and OS were significantly better in the high-dose group.

scholarly journals Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 Pneumonia: an open-label, randomised clinical trial

2021 ◽  
pp. 2102518
Author(s):  
Manuel Taboada ◽  
Nuria Rodríguez ◽  
Pablo Manuel Varela ◽  
María Teresa Rodríguez ◽  
Romina Abelleira ◽  
...  
Keyword(s):  
Dose Group ◽  
Oxygen Therapy ◽  
Low Dose ◽  
Ordinal Scale ◽  
High Dose Group ◽  
High Dose ◽  
Open Label ◽  
Once Daily ◽  
Significant Difference ◽  
Clinical Worsening

BackgroundLow dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high dose of dexamethasone is limited.MethodsWe performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low dose dexamethasone (6 mg once daily for 10 days) or high dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery, and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).ResultsA total of 200 patients (mean (sd) age, 64 (14) years; 62% male) were enrolled. Thirty-two patients of 102 (31.4%) enrolled in the low dose group and 16 of 98 (16.3%) in the high dose group showed clinical worsening within 11 days since randomisation (rate ratio, 0.427; 95% CI, 0.216–0.842; p=0.014). The 28-day mortality was 5.9% in the low dose group and 6.1% in the high dose group (p=0.844). There was no significant difference in time to recovery, and in the 7-point ordinal scale at day 5, 11, 14 and 28.ConclusionsAmong hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation as compared with low dose.

scholarly journals Efficacy of low dose pirfenidone in idiopathic pulmonary fibrosis: real world experience from a tertiary university hospital

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Myung Jin Song ◽  
Sung Woo Moon ◽  
Ji Soo Choi ◽  
Sang Hoon Lee ◽  
Su Hwan Lee ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Dose Reduction ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Significant Difference

AbstractPirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the efficacy of low-dose pirfenidone (that is, less than 1200 mg/day). We retrospectively reviewed the medical records of patients with IPF. The patients were divided into the following three groups, those who were not treated with pirfenidone (control) and those who were treated with pirfenidone at doses < 1200 mg/day (low-dose group) and ≥ 1200 mg/day (high-dose group). The adjusted mean changes in forced vital capacity (FVC) in 1 year were − 200.7, − 88.4, and − 94.7 mL in the control, low-dose, and high-dose groups (p = 0.021). The FVC declined more significantly in the control group than in the low-dose and high-dose groups. No significant difference in FVC change was observed between the low-dose and high-dose groups. Dyspepsia, anorexia, and nausea were significantly more frequent in the low-dose than in the high-dose group, suggesting that dose reduction is attributed to gastrointestinal tract-related adverse events. Dose reduction may help patients to better control gastrointestinal tract-related adverse events; continuing taking the medication at low doses is also expected to be effective in reducing the FVC decline.

High Dose Glucocorticoids in the Management of Severe Head Injury

Neurosurgery ◽  
1984 ◽  
Vol 15 (4) ◽  
pp. 497-501 ◽  
Author(s):  
Steven L. Giannotta ◽  
Martin H. Weiss ◽  
Michael L.J. Apuzzo ◽  
Evangeline Martin
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Sodium Succinate ◽  
Assisted Ventilation ◽  
High Dose Group ◽  
High Dose ◽  
Monitoring And Control ◽  
Methylprednisolone Sodium Succinate ◽  
Significant Difference ◽  
And Control

Abstract Eighty-eight patients with a Glasgow coma score of 8 or less 6 hours after nonpenetrating head trauma were given either high dose methylprednisolone sodium succinate (30 mg/kg q6h ×2, then 250 mg q6h ×6, then tapering over 8 days), low dose methylprednisolone (1.5 mg/kg q6h ×2, then 25 mg q6h ×6, then tapering over 8 days), or placebo. Standard care including the removal of traumatic hematomas, assisted ventilation, and intracranial pressure monitoring and control was carried out. Follow-up assessments were performed on all surviving patients at 6 months and were graded according to the Glascow outcome scale. No statistically significant difference in outcome was seen between the low dose group and the placebo group. The high dose group experienced a mortality of 39% as compared to a 52% mortality in the low dose and placebo groups (P &lt; 0.05). Mortality differences were most marked in patients less than 40 years old, with the high dose group experiencing a mortality of 6% as compared to a 43% mortality for the low dose and placebo groups (P &lt; 0.05). For patients under 50 years old, the incidence of recovery of speech was 62% compared to 36% in the low dose and placebo groups (P &lt; 0.5). The increased survival in those treated with high dose corticoids, however, was associated with an increase in the poorer outcome categories.

scholarly journals Effectiveness and Toxicity of Methotrexate in Juvenile Idiopathic Arthritis: Comparison of 2 Initial Dosing Regimens

2010 ◽  
Vol 37 (4) ◽  
pp. 870-875 ◽  
Author(s):  
MARA L. BECKER ◽  
CARLOS D. ROSÉ ◽  
RANDY Q. CRON ◽  
DAVID D. SHERRY ◽  
WARREN B. BILKER ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Response ◽  
Dose Group ◽  
Low Dose ◽  
Liver Toxicity ◽  
High Dose Group ◽  
High Dose ◽  
Active Joint ◽  
Significant Difference ◽  
Dosing Regimens

Objective.To compare the incidence of liver toxicity and clinical response between 2 initial dosing regimens of methotrexate (MTX) for treatment of juvenile idiopathic arthritis (JIA).Methods.Clinical and laboratory data were abstracted from the medical records of 220 children newly prescribed MTX from the same geographic region. One cohort received initial doses of MTX > 0.5 mg/kg/week (“high-dose”) and one cohort received initial doses of MTX ≤ 0.5 mg/kg/week (“low-dose”). Toxicity was defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above the normal range, and positive clinical response was defined as a reduction in active joint count during the first 6 months of MTX therapy.Results.One hundred twenty-six children were in the high-dose MTX group, 94 in the low-dose MTX group. At 6 months, the high-dose group was more likely to have an elevated AST or ALT (adjusted OR 3.89, 95% CI 1.82–8.29, p < 0.0001). Subjects receiving both MTX and nonsteroidal antiinflammatory drugs (NSAID) had no significant difference between groups in change of active joint count, while subjects in the high-dose group but not taking NSAID had more active joints (p = 0.036) at 6 months compared to the low-dose group.Conclusion.Initial high-dose MTX was associated with an increased risk of at least one liver enzyme abnormality with no significant improvement in active joint count. This suggests that there is no apparent benefit, while the potential for liver toxicity is increased, when using higher doses of MTX at treatment inception in patients with JIA.

Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin as First-Line Therapy for Advanced Gastric Cancer

Chemotherapy ◽  
2016 ◽  
Vol 61 (4) ◽  
pp. 197-203 ◽  
Author(s):  
Wenna Wang ◽  
Jing Huang ◽  
Yunxia Tao ◽  
Xiao Lyu ◽  
Lin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Significant Difference ◽  
Grade 3

Background: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. Methods: Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. Results: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. Conclusions: The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation.

scholarly journals Evaluation of Intra-Articular Injection of Bevacizumab on the Prevention of Physeal Bar Formation in Type 4 Salter Harris Model in Rats: A Pilot Study

2021 ◽  
Author(s):  
Zeinab Imani ◽  
Nesa Milan ◽  
Hossein Nematian ◽  
Leila Aghaghazvini ◽  
Mojtaba Sedaghat ◽  
...  
Keyword(s):  
Growth Plate ◽  
Dose Group ◽  
Low Dose ◽  
Preventive Treatment ◽  
High Dose Group ◽  
High Dose ◽  
Micro Computed Tomography ◽  
Significant Difference ◽  
Salter Harris ◽  
Bar Formation

Background: This study was designed to achieve a new method as a preventive treatment for complications of growth plate fractures. In this study, we investigate the effect of intra-articular injection of anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab on the repair process of articular cartilage in a type 4 Salter Harris injury model. Methods: A Salter Harris injury was created on the proximal tibial growth plate of 14 rats by a 1.8 mm drill. The rats were randomly classified into two groups: group LD, administration of high-dose intra-articular injection of bevacizumab (250 μg), and group HD, administration of low-dose intra-articular injection of bevacizumab (50 μg) after injury. The rats were killed 2 months postoperatively and their tibia underwent micro-computed tomography (CT) analysis, histological assessment, and measurement of tibial bone length. Results: Bony bar formation was observed in 71% of the samples in the high-dose group and in 100% of the low-dose group. Relative increase in physeal cartilage thickness (P = 0.007) and decrease in bony bar formation (P = 0.029) were observed significantly in the high dose group. There was no significant difference in tibia length between the two groups (P = 0.150). Conclusion: Intra-articular administration of bevacizumab demonstrated positive restorative effects. We suggest this method of treatment due to its potential of improving cartilage repair and capability to be used as a main or adjacent treatment in osteochondral defects.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Dose Group ◽  
Low Dose ◽  
Radioiodine Therapy ◽  
Meta Analysis ◽  
High Dose Group ◽  
High Dose ◽  
Fixed Effects Model ◽  
Recombinant Human Thyrotropin

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Sign in / Sign up

Export Citation Format

Share Document