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International Journal of Radiation... May 2021Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation....
PURPOSE
Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time.
METHODS AND MATERIALS
The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group.
RESULTS
Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/β = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%.
CONCLUSIONS
We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.
Topics: Dose-Response Relationship, Radiation; Humans; Linear Models; Male; Models, Biological; Models, Theoretical; Probability; Prostatic Neoplasms; Radiation Dose Hypofractionation; Radiosurgery; Relative Biological Effectiveness; Risk; Time Factors; Treatment Outcome; Urethra
PubMed: 32900561
DOI: 10.1016/j.ijrobp.2020.08.014 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
Health Physics Nov 2020A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine...
A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine relative to radiation quality of mixed neutron:gamma radiations, dose rate, and exposure uniformity relative to selected reference radiation exposure has not been performed. The datasets for rhesus macaques exposure to mixed neutron:gamma radiation are used herein as a species comparative reference to the canine database. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and US HHS RePORT (2002-present). The total number of hits across all search sites was 3,077. Several referenced, unpublished, non-peer reviewed government reports were unavailable for review. Primary published studies using canines, beagles, and mongrels were evaluated to provide an informative and consistent review of mixed neutron:gamma radiation effects to establish the DRRs for the H-ARS. Secondary and tertiary studies provided additional information on the hematologic response or the effects on hematopoietic progenitor cells, radiation dosimetry, absorbed dose, and organ dose. The LD50/30 values varied with neutron quality, exposure aspect, and mixed neutron:gamma ratio. The reference radiation quality varied from 250 kVp or 1-2 MeV x radiation and Co gamma radiation. A summary of a published review of a data set describing the DRR in rhesus macaques for mixed neutron:gamma radiation exposure in the H-ARS is included for a comparative reference to the canine dataset. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in canines and young rhesus macaques exposed to mixed neutron:gamma radiations of variable energy relative to 250 kVp, 1-2 MeV x radiation and Co gamma, and uniform and non-uniform total-body irradiation without the benefit of medical management. The mixed neutron:gamma radiation showed an energy-dependent RBE of ~ 1.0 to 2.0 relative to reference radiation exposure within both species. A marginal database described the DRR for the gastrointestinal (GI)-ARS. Medical management showed benefit in both species relative to the mixed neutron:gamma as well as exposure to reference radiation. The DRR for the H-ARS was characterized by steep slopes and relative LD50/30 values that reflected the radiation quality, exposure aspect, and dose rate over a range in time from 1956-2012.
Topics: Acute Radiation Syndrome; Animals; Dogs; Dose-Response Relationship, Radiation; Gamma Rays; Hematopoietic Stem Cells; Neutrons; Primates; Radiation Exposure; Reference Standards
PubMed: 32947486
DOI: 10.1097/HP.0000000000001319 -
Cureus May 2024Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of... (Review)
Review
Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of autoantibodies against the thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR), which mimic the effects of the hormone on thyroid cells, thereby stimulating autonomic production of thyroxine and triiodothyronine. Deciding on a therapeutic approach to this condition presents intricate dilemmas for both clinicians and patients. Each of the three available treatment modalities is grounded in evidence-based medicine, affirming its efficacy. This systematic review and meta-analysis aimed to assess the effect of carbimazole (CBM), radioactive iodine (RAI), and surgery in treating GD and provide evidence-based recommendations for healthcare providers regarding the optimal management of the condition based on a comprehensive analysis of effectiveness, safety, patient satisfaction, and recovery outcomes. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and September 2023. The meta-analysis was carried out using Resource Manager (Revman) 5.4.1. The study found that propylthiouracil (PTU) or methimazole/carbimazole (MMI/CBM) treatment increases the risk of hyperlipidemia in patients with hyperthyroidism. Once in a euthyroid state, glucose tolerance increases; for children with GD, a computer model for customized dosing has been created. To sum up, CBM, surgery, and RAI are all useful treatment options for GD. Using steroids in conjunction with radiation therapy may help prevent Graves' ophthalmopathy (GO).
PubMed: 38910658
DOI: 10.7759/cureus.60829 -
Journal of Cancer Research and... 2020In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the...
In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the term "FLASH" radiotherapy (RT). Thus, in the present study, we systematically review these recent studies on FLASH RT with regard to its efficacy and safety. The reporting of this systematic review was done in line with the statement of Preferred Reporting Items for Systematic reviews and Meta-Analyses. Electronic search of the databases such as PubMed, Scopus, and Embase was conducted to retrieve relevant studies investigating the FLASH effect. From an initial search of 216 potential articles, 16 articles (in vivo, in vitro , and clinical studies) were finally included in this systematic review. Results showed that FLASH RT dose rates had protective effects on normal tissues in addition to antitumor effect. Although still in its early research stages, FLASH RT has the potential to rival present RT regimens in terms of safety and antitumor effect. However, further studies are needed to address the aspects such as optimal dose rate, effect on deep tumors, tumor recurrence, longer follow-up time, and mechanism of action.
Topics: Humans; Neoplasms; Organ Sparing Treatments; Radiation Oncology; Radiation Tolerance; Radiotherapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Treatment Outcome
PubMed: 33342774
DOI: 10.4103/jcrt.JCRT_180_20 -
Radiotherapy and Oncology : Journal of... Sep 2019The limited radiation tolerance of the small-bowel causes toxicity for patients receiving conventionally-fractionated radiotherapy for rectal cancer. Safe radiotherapy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The limited radiation tolerance of the small-bowel causes toxicity for patients receiving conventionally-fractionated radiotherapy for rectal cancer. Safe radiotherapy dose-escalation will require a better understanding of such toxicity. We conducted a systematic review and meta-analysis using published datasets of small bowel dose-volume and outcomes to analyse the relationship with acute toxicity.
MATERIALS AND METHODS
SCOPUS, EMBASE & MEDLINE were searched to identify twelve publications reporting small-bowel dose-volumes and toxicity data or analysis. Where suitable data were available (mean absolute volume with parametric error measures), fixed-effects inverse-variance meta-analysis was used to compare cohorts of patients according to Grade ≥3 toxicity. For other data, non-parametric examinations of irradiated small-bowel dose-volume and incidence of toxicity were conducted, and a univariate logistic regression model was fitted.
RESULTS
On fixed-effects meta-analysis of three studies (203 patients), each of the dose-volume measures V-V were significantly greater (p < 0.00001) for patients with Grade ≥3 toxicity than for those without. Absolute difference was largest for the lowest dose-volume parameter; however relative difference increases with increasing dose. On logistic regression multiple small-bowel DVH parameters were predictive of toxicity risk (V, V, V - V), with V the strongest (p = 0.004).
CONCLUSIONS
Analysis of published clinical cohort dose-volume data provides evidence for a significant dose-volume-toxicity response effect for a wide range of clinically-relevant doses in the treatment of rectal cancer. Both low dose and high dose are shown to predict toxicity risk, which has important implications for radiotherapy planning and consideration of dose escalation for these patients.
Topics: Dose Fractionation, Radiation; Humans; Intestine, Small; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms
PubMed: 31136961
DOI: 10.1016/j.radonc.2019.05.001 -
Leukemia Research Sep 2021Non-Hodgkin's lymphoma continues to be a highly prevalent entity in the general population. Currently, there are multiple treatment schemes based on chemotherapeutic... (Review)
Review Meta-Analysis
Non-Hodgkin's lymphoma continues to be a highly prevalent entity in the general population. Currently, there are multiple treatment schemes based on chemotherapeutic agents with a great success rate. However, there is a non-negligible percentage of patients who may relapse or be refractory. In this sense, new therapeutic options have emerged in the search for adequate responses, such as monoclonal antibodies that target the CD20 molecule. Another valid option is radioimmunotherapy (RIT), which combines using monoclonal antibodies for the specific targeting of malignant cells and radiation to destroy these cells. Despite the promising results that favor RIT in several clinical studies in different target populations and types of NHL, one situation to consider is the association of this therapy and second neoplasms (acute myeloid leukemia (AML) or myelodysplastic syndrome (MSD)). In this sense, we have proposed this meta-analysis to analyze the published information and determine the incidence of this association and determine this therapy's safety.
Topics: Humans; Lymphoma, Non-Hodgkin; Radiation Tolerance; Radioimmunotherapy; Treatment Outcome
PubMed: 34052662
DOI: 10.1016/j.leukres.2021.106615 -
Oral Oncology Jan 2020Post-radiotherapy head and neck cancer patients are at increased risk of dental caries due to radiotherapy-induced salivary gland hypofunction and radiation-damage to...
Post-radiotherapy head and neck cancer patients are at increased risk of dental caries due to radiotherapy-induced salivary gland hypofunction and radiation-damage to tooth structure. Dental caries may cause pain and discomfort, and is likely to have a detrimental impact on patients' quality of life. This systematic review appraised and synthesised best available evidence regarding the incidence and severity of post-radiotherapy dental caries in head and neck cancer patients. Six databases and two trial registries were searched from their inception to May 2019. A total of 22 papers met the inclusion criteria. The pooled percentage of patients that developed dental caries post-radiotherapy was 29% (n = 15 studies; 95% CI 21%, 39%; I = 88.0%). Excluding studies with longer than two years follow-up, the pooled percentage was 37% (n = 9 studies; 95% CI 25%, 51%; I = 88.6%). Meta-regression analysis revealed that studies with a higher mean/median radiotherapy dose exposure, had an increased incidence of dental caries (p = 0.02). Furthermore, studies with a higher proportion of patients treated with chemotherapy in addition to radiotherapy, had an increased incidence of dental caries (p = 0.02) after the exclusion of an outlier. It is important to be mindful of the high degree of observed heterogeneity and the inclusion of a large number of non-randomised studies. Data regarding the number of carious teeth, the number of carious tooth surfaces, and the number of carious lesions developed post-radiotherapy was unsuitable for meta-analysis. There is a need for well-designed research studies to improve understanding of dental caries-risk in post-radiotherapy head and neck cancer patients.
Topics: Chemoradiotherapy; Dental Caries; Dose-Response Relationship, Radiation; Head and Neck Neoplasms; Humans; Incidence; Quality of Life; Radiotherapy; Severity of Illness Index
PubMed: 31786391
DOI: 10.1016/j.oraloncology.2019.104484 -
EClinicalMedicine Oct 2023Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear...
Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis.
BACKGROUND
Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear whether there is ethnic difference in the incidence of post-CRT pneumonitis.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies from January 1, 2000 to April 30, 2023. The outcomes of interest were incidence rates of pneumonitis. The random-effect model was used for statistical analysis. This meta-analysis was registered with PROSPERO (CRD42023416490).
FINDINGS
A total of 248 studies involving 28,267 patients were included. Among studies of CRT without immunotherapy, the pooled rates of pneumonitis for Asian patients were significantly higher than that for non-Asian patients (all grade: 66.8%, 95% CI: 59.2%-73.9% vs. 28.1%, 95% CI: 20.4%-36.4%; P < 0.0001; grade ≥2: 25.1%, 95% CI: 22.9%-27.3% vs. 14.9%, 95% CI: 12.0%-18.0%; P < 0.0001; grade ≥3: 6.5%, 95% CI: 5.6%-7.3% vs. 4.6%, 95% CI: 3.4%-5.9%; P = 0.015; grade 5: 0.6%, 95% CI: 0.3%-0.9% vs. 0.1%, 95% CI: 0.0%-0.2%; P < 0.0001). Regarding studies of CRT plus immunotherapy, Asian patients had higher rates of all-grade (74.8%, 95% CI: 63.7%-84.5% vs. 34.3%, 95% CI: 28.7%-40.2%; P < 0.0001) and grade ≥2 (34.0%, 95% CI: 30.7%-37.3% vs. 24.6%, 95% CI: 19.9%-29.3%; P = 0.001) pneumonitis than non-Asian patients, but with no significant differences in the rates of grade ≥3 and grade 5 pneumonitis. Results from subgroup analyses were generally similar to that from the all studies. In addition, the pooled median/mean of lung volume receiving ≥20 Gy and mean lung dose were relatively low in Asian studies compared to that in non-Asian studies.
INTERPRETATION
Asian patients are likely to have a higher incidence of pneumonitis than non-Asian patients, which appears to be due to the poor tolerance of lung to radiation. Nevertheless, these findings are based on observational studies and with significant heterogeneity, and need to be validated in future large prospective studies focusing on the subject.
FUNDING
None.
PubMed: 37781162
DOI: 10.1016/j.eclinm.2023.102246 -
Clinical Oncology (Royal College of... Jan 2021Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment... (Meta-Analysis)
Meta-Analysis
AIMS
Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment paradigms. Radiotherapy boost has been linked to higher rates of pCR; however, outcomes in moderately escalated inverse-planning studies have not been systematically evaluated. We therefore carried out a systematic review and meta-analysis of radiation dose-escalation studies in the context of neoadjuvant therapy for locally advanced rectal cancer.
MATERIALS AND METHODS
A systematic search of Pubmed, EMBASE and Cochrane databases for synonyms of 'rectal cancer', 'radiotherapy' and 'boost' was carried out. Studies were screened for radiotherapy prescription >54 Gy. Prespecified quality assessment was carried out for meta-analysis inclusion suitability. Pooled estimates of pCR, acute toxicity (grade ≥3) and R0 resection rates were determined with random-effects restricted maximum-likelihood estimation. Heterogeneity was assessed with Higgins I and Cochran Q statistic. Subset analysis examined outcomes in modern inverse-planning studies. Meta-regression with permutation correction was carried out for each outcome against radiation dose, radiotherapy technique, boost technique, chemotherapy intensification and other patient- and treatment-related cofactors.
RESULTS
Forty-nine primary and three follow-up publications were included in the systematic review. Pooled estimates of pCR, toxicity and R0 resection across 37 eligible publications (n = 1817 patients) were 24.1% (95% confidence interval 21.2-27.4%), 11.2% (95% confidence interval 7.2-17.0%) and 90.7% (95% confidence interval 87.9-93.8%). Within inverse-planning studies (17 publications, n = 959 patients), these rates were 25.7% (95% confidence interval 21.0-31.1%), 9.8% (95% confidence interval 4.6-19.7%) and 95.3% (95% confidence interval 91.6-97.4%). Regression analysis did not identify any significant predictor of pCR (P > 0.05).
CONCLUSIONS
Radiotherapy dose escalation above 54 Gy is associated with high rates of pCR and does not seem to increase the risk of acute grade ≥3 toxicity events. pCR rates approaching 25% may be achievable utilising moderate escalation (54-60 Gy) with modern inverse-planning techniques; however, a clear dose-response relationship was not identified in regression analysis and additional evidence is awaited given the prevalence of heterogenous single-arm studies to date.
Topics: Dose-Response Relationship, Radiation; Humans; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms
PubMed: 32669228
DOI: 10.1016/j.clon.2020.06.008