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Radiotherapy and Oncology : Journal of... Aug 2015A recent update of the RTOG 9811, reported differing relapse rates for early and late anal squamous cell carcinoma following chemoradiotherapy (CRT). There may be a role... (Review)
Review
BACKGROUND AND PURPOSE
A recent update of the RTOG 9811, reported differing relapse rates for early and late anal squamous cell carcinoma following chemoradiotherapy (CRT). There may be a role for dose-individualization, however the dose-response relationship for anal cancer is not currently known. Intensity-modulated radiotherapy (IMRT) has been widely adopted with multiple series published. The aim is to fit a tumor control probability (TCP) model to the published IMRT data.
MATERIALS AND METHODS
We performed a systematic review of PubMed and Embase databases to identify thirteen appropriate papers, including 625 patients. Predefined data fields were collected. A standard linear quadratic TCP model, which included repopulation, was fit by least squares minimization.
RESULTS
The fitted TCP curve demonstrated a dose-response relationship with α=0.196 Gy(-1). The curve suggests: in early stage tumours, a dose reduction from 50 Gy to 45 Gy reduces 2 year local control from 98% to 95%; in late stage tumours, a dose escalation from 50 Gy to 55 Gy improves the 2 year local control rate from approximately 50% to 80%.
CONCLUSIONS
The published data are broadly consistent with a linear quadratic dose-response model. Dose-individualization in anal cancer should be further investigated in the context of clinical trials.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Dose-Response Relationship, Radiation; Humans; Least-Squares Analysis; Linear Models; Neoplasm Recurrence, Local; Probability; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated
PubMed: 26243680
DOI: 10.1016/j.radonc.2015.07.014 -
The Cochrane Database of Systematic... Jul 2018Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality... (Review)
Review
BACKGROUND
Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality of life (QoL) and function. The underlying pathophysiological mechanism remains unclear for this condition, which makes establishing effective treatments challenging.
OBJECTIVES
To assess the effectiveness of interventions used for the treatment of brain radionecrosis in adults over 18 years old.
SEARCH METHODS
In October 2017, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for eligible studies. We also searched unpublished data through Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials for ongoing trials and handsearched relevant conference material.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any intervention directed to treat brain radionecrosis in adults over 18 years old previously treated with radiation therapy to the brain. We anticipated a limited number of RCTs, so we also planned to include all comparative prospective intervention trials and quasi-randomised trials of interventions for brain radionecrosis in adults as long as these studies had a comparison group that reflects the standard of care (i.e. placebo or corticosteroids). Selection bias was likely to be an issue in all the included non-randomised studies therefore results are interpreted with caution.
DATA COLLECTION AND ANALYSIS
Two review authors (CC, PB) independently extracted data from selected studies and completed a 'Risk of bias' assessment. For dichotomous outcomes, the odds ratio (OR) for the outcome of interest was reported. For continuous outcomes, treatment effect was reported as mean difference (MD) between treatment arms with 95% confidence intervals (CIs).
MAIN RESULTS
Two RCTs and one prospective non-randomised study evaluating pharmacological interventions met the inclusion criteria for this review. As each study evaluated a different drug or intervention using different endpoints, a meta-analysis was not possible. There were no trials of non-pharmacological interventions that met the inclusion criteria.A very small randomised, double-blind, placebo-controlled trial of bevacizumab versus placebo reported that 100% (7/7) of participants on bevacizumab had reduction in brain oedema by at least 25% and reduction in post-gadolinium enhancement, whereas all those receiving placebo had clinical or radiological worsening or both. This was an encouraging finding but due to the small sample size we did not report a relative effect. The authors also failed to provide adequate details regarding the randomisation and blinding procedures Therefore, the certainty of this evidence is low and a larger RCT adhering to reporting standards is needed.An open-label RCT demonstrated a greater reduction in brain oedema (T2 hyperintensity) in the edaravone plus corticosteroid group than in the corticosteroid alone group (MD was 3.03 (95% CI 0.14 to 5.92; low-certainty evidence due to high risk of bias and imprecision); although the result approached borderline significance, there was no evidence of any important difference in the reduction in post-gadolinium enhancement between arms (MD = 0.47, 95% CI - 0.80 to 1.74; low-certainty evidence due to high risk of bias and imprecision).In the RCT of bevacizumab versus placebo, all seven participants receiving bevacizumab were reported to have neurological improvement, whereas five of seven participants on placebo had neurological worsening (very low-certainty evidence due to small sample size and concerns over validity of analyses). While no adverse events were noted with placebo, three severe adverse events were noted with bevacizumab, which included aspiration pneumonia, pulmonary embolus and superior sagittal sinus thrombosis. In the RCT of corticosteroids with or without edaravone, the participants who received the combination treatment were noted to have significantly greater clinical improvement than corticosteroids alone based on LENT/SOMA scale (OR = 2.51, 95% CI 1.26 to 5.01; low-certainty evidence due to open-label design). No differences in treatment toxicities were observed between arms.One included prospective non-randomised study of alpha-tocopherol (vitamin E) versus no active treatment was found but it did not include any radiological assessment. As only one included study was a double-blinded randomised controlled trial, the other studies were prone to selection and detection biases.None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements.A limited number of prospective studies were identified but subsequently excluded as these studies had a limited number of participants evaluating different pharmacological interventions using variable endpoints.
AUTHORS' CONCLUSIONS
There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.
Topics: Adrenal Cortex Hormones; Adult; Antipyrine; Bevacizumab; Brain; Brain Edema; Drug Therapy, Combination; Edaravone; Gadolinium; Humans; Non-Randomized Controlled Trials as Topic; Radiation Injuries; Radiosurgery; Radiotherapy; Randomized Controlled Trials as Topic
PubMed: 29987845
DOI: 10.1002/14651858.CD011492.pub2 -
Cancer Treatment Reviews Nov 2022Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet need to define... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet need to define indications, prescription doses and potential adverse events of protons in this clinical scenario. Hence, the present work aims to provide a critical literature revision, and to investigate associations between fractionation schedules/ biological effective doses (BEDs), oncological outcomes and toxicities.
MATERIALS AND METHODS
This systematic review and meta-analysis complied with the PRISMA recommendations. Inclusion criteria were: 1) curative-intent hypofractionated PBT for ES-NSCLC (≥3 Gy(RBE)/fraction), 2) report of the clinical outcomes of interest, 3) availability of full-text written in English. The bibliographic search was performed on the NCBI Pubmed, Embase and Scopus in September 2021; no other limitations were applied. The BED was calculated for each included study (α/β = 10 Gy); the median BED for all studies was used as a threshold for stratifying selected evidence into "high" and "low"-dose subgroups. Heterogeneity was tested using chi-square statistics; inconsistency was measured with the I index. Pooled estimate was obtained by fitting both the fixed-effect and the DerSimonian and Laird random-effect model.
RESULTS
Eight studies and 401 patients were available for the meta-analysis; median follow-up was 32.8 months. The median delivered BED was 105.6 Gy(RBE). A BED ≥ 105.6 Gy(RBE) consistently provided superior OS, CSS, DFS and LC rates (i.e.: 4-year OS: 0.56 [0.34-0.76] for BED < 105.6 Gy(RBE) and 0.78 [0.64-0.88] for BED ≥ 105.6 Gy(RBE)). The meta-analysis of proportions showed a comparable probability of developing acute grade ≥ 2 toxicity between the two groups, while the probability of any late grade ≥ 2 event was almost three-times greater for BED ≥ 105.6 Gy(RBE), with rib fractures being more common in the high dose group.
CONCLUSION
Hypofractionated PBT is a safe and effective treatment option for ES-NSCLC; the delivery of BED ≥ 105.6 Gy(RBE) with advanced techniques for uncertainty management has been associated with improved oncological outcomes across all considered time points.
Topics: Carcinoma, Non-Small-Cell Lung; Dose Fractionation, Radiation; Humans; Lung Neoplasms; Proton Therapy; Protons
PubMed: 36194908
DOI: 10.1016/j.ctrv.2022.102464 -
Advances in Radiation Oncology 2020Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review...
PURPOSE
Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT.
METHODS AND MATERIALS
A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation.
RESULTS
Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS.
CONCLUSIONS
Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.
PubMed: 33083660
DOI: 10.1016/j.adro.2020.04.022 -
Acta Oncologica (Stockholm, Sweden) Dec 2019Hepatocellular carcinoma (HCC) incidence is rising worldwide, especially due to increased detection of early-stage or small-sized tumors. Nevertheless, most of the...
Hepatocellular carcinoma (HCC) incidence is rising worldwide, especially due to increased detection of early-stage or small-sized tumors. Nevertheless, most of the patients are still not qualified for surgical resection at diagnosis due to the localization of the tumor, underlying liver disease or comorbidities. Stereotactic body radiation therapy (SBRT) is a radiotherapy modality which can deliver a high dose of radiation to the target tissue with a high degree of precision. It shows promise in terms of efficacy and morbidity. The aim of this systematic review is to summarize current knowledge on patient-specific outcomes of SBRT for small HCC including overall survival, local control, the effect of dose escalation and the toxicity of the treatment. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After a comprehensive database search, 16 studies (973 patients with 1034 lesions) were included in qualitative and quantitative analyses; 14 of them were retrospective. Average tumor diameter was 23 mm and 95% of patients were in good general condition. Median BED10 (biologically equivalent dose calculated for α/β ratio of 10 Gy) was 100 Gy (range 59.5-180 Gy). Mean weighted local control across studies was 94%, 92% and 93% at 1, 2, and 3 years, respectively. Mean weighted overall survival across studies was 90.9%, 67.5% and 73.4% at 1, 2, and 3 years, respectively. There were 171 grade 1-2 toxicities (17.5%) and 53 ≥ grade 3 toxicities (5.3%). There was no treatment-associated mortality. SBRT offers high local control with overall survival that is comparable with radiofrequency ablation and surgery. Quality of findings, especially on toxicities, is decreased by incomplete reporting and retrospective designs of published studies. Therefore, there is a need for better reporting and prospective studies to univocally recommend SBRT as a definitive treatment option in the guidelines for small HCCs.
Topics: Aged; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Models, Statistical; Prospective Studies; Radiosurgery; Radiotherapy Dosage; Retrospective Studies; Treatment Outcome; Tumor Burden
PubMed: 31464155
DOI: 10.1080/0284186X.2019.1657942 -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474 -
Cureus Jun 2024Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One... (Review)
Review
Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX). This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC. This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases. Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group. In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.
PubMed: 38835557
DOI: 10.7759/cureus.61547 -
Radiotherapy and Oncology : Journal of... Mar 2015To perform a systematic review and meta-analysis to compare the clinical outcomes and toxicity of hepatocellular carcinoma (HCC) patients treated with charged particle... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To perform a systematic review and meta-analysis to compare the clinical outcomes and toxicity of hepatocellular carcinoma (HCC) patients treated with charged particle therapy (CPT) with those of individuals receiving photon therapy.
METHODS
We identified relevant clinical studies through searching databases. Primary outcomes of interest were overall survival (OS) at 1, 3, 5 years, progression-free survival (PFS), and locoregional control (LC) at longest follow-up.
RESULTS
73 cohorts from 70 non-comparative observational studies were included. Pooled OS was significantly higher at 1, 3, 5 years for CPT than for conventional radiotherapy (CRT) [relative risk (RR) 1·68, 95% CI 1·22-2·31; p<0·001; RR 3.46, 95% CI: 1.72-3.51, p<0.001; RR 25.9, 95% CI: 1.64-408.5, p=0.02; respectively]. PFS and LC at longest follow-up was also significantly higher for CPT than for CRT (p=0·013 and p<0.001, respectively), while comparable efficacy was found between CPT and SBRT in terms of OS, PFS and LC at longest follow-up. Additionally, high-grade acute and late toxicity associated with CPT was lower than that of CRT and SBRT.
CONCLUSION
Survival rates for CPT are higher than those for CRT, but similar to SBRT in patients with HCC. Toxicity tends to be lower for CPT compared to photon radiotherapy.
Topics: Alpha Particles; Carcinoma, Hepatocellular; Cohort Studies; Disease-Free Survival; Humans; Liver Neoplasms; Observational Studies as Topic; Photons; Survival Rate
PubMed: 25497556
DOI: 10.1016/j.radonc.2014.11.033 -
Journal of Environmental Radioactivity Aug 2022Solid mineral mining activities have contributed to the distribution and uptake of radionuclides. This has increased the active concentration of naturally occurring... (Review)
Review
Solid mineral mining activities have contributed to the distribution and uptake of radionuclides. This has increased the active concentration of naturally occurring radioactive materials NORMs in different environmental media with increased human health risks. This systematic review was aimed at assessing data on active concentration of naturally occurring radioactive materials in mining sites in Nigeria. Articles available on recognized data bases such as Google scholar, PubMed, Cochrane Library and Science Direct were used. Thirty-two studies were used for this systematic review after meeting the inclusion criteria. Reports of studies according to Geopolitical zones revealed 0% North-east, 4% for Southeast, 8% for South-South, 16% in North-West, 20% in South-West, and 52% from North-Central Nigeria. 50%, 45.2%, 50%, and 38.5% of included studies reported elevated active concentration of Th, K, U and Ra in soil above world regulatory standards of the ICRP, UNSCEAR and IAEA. Gross-alpha and gross-beta activity concentrations reference dose level (RDL) were exceeded in 83.3% and 80% of studies respectively with the highest values recorded in water 10.12Bq/l, and 14.63Bq/l from an artisanal gold mine in North-West Nigeria. These data agree with reports from other African countries, but lower than reports from China and India. NORMs may be of public health concerns notwithstanding the lean data from clinical and epidemiological studies in Nigeria. This study recommends a One Health approach on the radiological implications of mining sites in Nigeria.
Topics: Humans; Public Health; Nigeria; Radiation Monitoring; Radioisotopes; Soil Pollutants, Radioactive
PubMed: 35525078
DOI: 10.1016/j.jenvrad.2022.106889 -
Clinical & Translational Oncology :... Aug 2017To review the use of brachytherapy as an adjuvant therapy to reduce recurrences after sublobar resections and as a palliation to patients with inoperable disease. Α... (Review)
Review
To review the use of brachytherapy as an adjuvant therapy to reduce recurrences after sublobar resections and as a palliation to patients with inoperable disease. Α review of all published studies was performed to identify the recurrence rate after brachytherapy adjuvant to sublobar resection and assess the palliation of symptoms and the complications of brachytherapy as a palliative treatment. Most of the studies that we found about brachytherapy as an adjuvant therapy to sublobar resection due to patient's poor cardiopulmonary reserve showed that brachytherapy offered low recurrence rate with low toxicity. Ten studies concerning palliative brachytherapy showed improvement of symptoms with good tolerance and good endoscopic response rates. Literature suggests that brachytherapy for inoperable symptomatic disease can be delivered for symptom improvement with acceptable toxicity. Brachytherapy as an alternative treatment option for lung cancer needs more investigation with more prospective trials.
Topics: Brachytherapy; Humans; Lung Neoplasms; Prognosis
PubMed: 28255649
DOI: 10.1007/s12094-017-1635-0