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The British Journal of Radiology Jan 2019Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater...
Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Four randomised trials testing fraction sizes in the range 2.7-3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week.
Topics: Breast Neoplasms; Female; Humans; Lymphatic Metastasis; Mastectomy; Mastectomy, Segmental; Middle Aged; Neoplasm Recurrence, Local; Radiation Dose Hypofractionation; Radiotherapy, Adjuvant
PubMed: 29345152
DOI: 10.1259/bjr.20170849 -
Journal of the American Academy of... Mar 2021
Meta-Analysis
Incidence of dermatologic adverse events in patients with cancer treated with concurrent immune checkpoint inhibitors and radiation therapy: A systematic review and meta-analysis.
Topics: Chemoradiotherapy; Clinical Trials as Topic; Drug Eruptions; Humans; Immune Checkpoint Inhibitors; Incidence; Neoplasms; Radiodermatitis
PubMed: 33137440
DOI: 10.1016/j.jaad.2020.10.071 -
World Journal of Urology Nov 2023Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy...
PURPOSE
Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity.
METHOD
A systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: "urethra-steering" SBRT (restriction of hotspots to the urethra) and "urethra dose-reduction" SBRT (dose reduction to urethra below the prescribed dose).
RESULTS
By limiting the urethra D to 90GyEQD2 (α/β = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years.
CONCLUSION
US-SBRT techniques limiting maximum doses to urethra below a 90Gy (α/β = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.
Topics: Male; Humans; Urethra; Radiosurgery; Neoplasm Recurrence, Local; Prostatic Neoplasms; Urogenital System
PubMed: 37668718
DOI: 10.1007/s00345-023-04579-6 -
International Journal of Radiation... Dec 2018The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms...
PURPOSE
The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms after external beam radiation therapy (EBRT) alone and treatments involving brachytherapy (BT) for prostate cancer after Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and ultimately to perform quantitative syntheses of identified dose/volume tolerances represented by dose-volume histogram (DVH) thresholds, that is, statistically significant (P ≤ .05) cutoff points between symptomatic and asymptomatic patients in a certain study.
METHODS AND MATERIALS
PubMed was scrutinized for full-text articles in English after QUANTEC (January 1, 2010). The inclusion criteria were randomized controlled trials, case-control studies, or cohort studies with tolerance doses for late distinct symptoms ≥3 months after primary radiation therapy for prostate cancer (N > 30). All DVH thresholds were converted into equivalent doses in 2-Gy fractions (EQD2) and were fitted with a linear or linear-quadratic function (goodness of fit, R). The review was registered on PROSPERO (CRD42016042464).
RESULTS
From 33 identified studies, which included 36 to 746 patients per symptom domain, the majority of dose/volume tolerances were derived for GI toxicity after EBRT alone (GI, 97 thresholds; GU, 8 thresholds; SD, 1 threshold). For 5 symptoms (defecation urgency, diarrhea, fecal incontinence, proctitis, and rectal bleeding), relationships between dose/volume tolerances across studies (R = 0.93 [0.82-1.00]), and across symptoms, leading to a curve for overall GI toxicity (R = 0.98), could be determined. For these symptoms, mainly rectal thresholds were found throughout low and high doses (10 Gy ≤ equivalent dose in 2-Gy fractions using α/β = 3Gy (EQD2) ≤ 50 Gy and 55 Gy ≤ EQD2 ≤ 78 Gy, respectively). For BT with or without EBRT, dose/volume tolerances were also mainly identified for GI toxicity (GI, 14 thresholds; GU, 4 thresholds; SD, 2 thresholds) with the largest number of DVH thresholds concerning rectal bleeding (5 thresholds).
CONCLUSIONS
Updated dose/volume tolerances after QUANTEC were found for 17 GI, GU, or SD symptoms. A DVH curve described the relationship between dose/volume tolerances across 5 GI symptoms after EBRT alone. Restricting treatments for EBRT alone using the lower boundaries of this curve is likely to limit overall GI toxicity, but this should be explored prospectively. Dose/volume tolerances for GU and SD toxicity after EBRT alone and after BT with or without EBRT were scarce and support further research including data-sharing initiatives to untangle the dose/volume relationships for these symptoms.
Topics: Humans; Male; Prostatic Neoplasms; Radiation Dosage; Radiotherapy; Radiotherapy Dosage; Safety
PubMed: 30125635
DOI: 10.1016/j.ijrobp.2018.08.015 -
Clinical Orthopaedics and Related... Nov 2016Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range... (Review)
Review
BACKGROUND
Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range of orthopaedic applications. In bulk form, PEEK composites are generally accepted as biocompatible. In particulate form, however, the biologic response relevant to joint replacement devices remains unclear. The biologic response to wear particles affects the longevity of total joint arthroplasties. Particles in the phagocytozable size range of 0.1 µm to 10 µm are considered the most biologically reactive, particularly particles with a mean size of < 1 µm. This systematic review aimed to identify the current evidence for the biologic response to PEEK-based wear debris from total joint arthroplasties.
QUESTIONS/PURPOSES
(1) What are the quantitative characteristics of PEEK-based wear particles produced by total joint arthroplasties? (2) Do PEEK wear particles cause an adverse biologic response when compared with UHMWPE or a similar negative control biomaterial? (3) Is the biologic response affected by particle characteristics?
METHODS
Embase and Ovid Medline databases were searched for studies that quantified PEEK-based particle characteristics and/or investigated the biologic response to PEEK-based particles relevant to total joint arthroplasties. The keyword search included brands of PEEK (eg, MITCH, MOTIS) or variations of PEEK types and nomenclature (eg, PAEK, CFR-PEEK) in combination with types of joint (eg, hip, knee) and synonyms for wear debris or immunologic response (eg, particles, cytotoxicity). Peer-reviewed studies, published in English, investigating total joint arthroplasty devices and cytotoxic effects of PEEK particulates were included. Studies investigating devices without articulating bearings (eg, spinal instrumentation devices) and bulk material or contact cytotoxicity were excluded. Of 129 studies, 15 were selected for analysis and interpretation. No studies were found that isolated and characterized PEEK wear particles from retrieved periprosthetic human tissue samples.
RESULTS
In the four studies that quantified PEEK-based particles produced using hip, knee, and spinal joint replacement simulators, the mean particle size was 0.23 µm to 2.0 µm. The absolute range reported was approximately 0.01 µm to 50 µm. Rod-like carbon particulates and granular-shaped PEEK particles were identified in human tissue by histologic analysis. Ten studies, including six animal models (rat, mouse, and rabbit), three cell line experiments, and two human tissue retreival studies, investigated the biologic response to PEEK-based particles. Qualitative histologic assessments showed immunologic cell infiltration to be similar for PEEK particles when compared with UHMWPE particles in all six of the animal studies identified. However, increased inflammatory cytokine release (such as tumor necrosis factor-α) was identified in only one in vitro study, but without substantial suppression in macrophage viability. Only one study tested the effects of particle size on cytotoxicity and found the largest unfilled PEEK particles (approximately 13 µm) to have a toxic effect; UHMWPE particles in the same size range showed a similar cytotoxic effect.
CONCLUSIONS
Wear particles produced by PEEK-based bearings were, in almost all cases, in the phagocytozable size range (0.1-10 µm). The studies that evaluated the biologic response to PEEK-based particles generally found cytotoxicity to be within acceptable limits relative to the UHMWPE control, but inconsistent when inflammatory cytokine release was considered.
CLINICAL RELEVANCE
To translate new and advanced materials into clinical use more quickly, the clinical relevance and validity of preclinical tests need to be improved. To achieve this for PEEK-based devices, human tissue retrieval studies including subsequent particle isolation and characterization analyses are required. In vitro cell studies using isolated wear particles from tissue or validated joint replacement simulators, instead of manufactured particles, are also required.
Topics: Animals; Arthroplasty, Replacement; Benzophenones; Cytokines; Foreign-Body Reaction; Humans; Inflammation Mediators; Joint Prosthesis; Ketones; Particle Size; Phagocytosis; Polyethylene Glycols; Polyethylenes; Polymers; Prosthesis Design; Prosthesis Failure; Risk Factors; Stress, Mechanical; Treatment Outcome
PubMed: 27432420
DOI: 10.1007/s11999-016-4976-z -
Radiotherapy and Oncology : Journal of... Mar 2018To compare cosmesis and local recurrence (LR) of definitive external beam radiation therapy (EBRT) vs brachytherapy (BT) for indolent basal cell carcinoma (BCC) and... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND PURPOSE
To compare cosmesis and local recurrence (LR) of definitive external beam radiation therapy (EBRT) vs brachytherapy (BT) for indolent basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin.
MATERIALS AND METHODS
Studies including patients with T1-2 N0 SCCs/BCCs treated with definitive EBRT/BT and ≥10 months follow-up were analyzed. The primary endpoint was post-treatment cosmesis, categorized as "good," "fair," or "poor." The secondary endpoint was LR. Mixed effects regression models were used to estimate weighted linear relationships between biologically equivalent doses with α/β = 3 (BED) and cosmetic outcomes.
RESULTS
A total of 9965 patients received EBRT and 553 received BT across 24 studies. Mean age was 73 years, median follow-up was 36 months, and median dose was 45 Gy/10 fractions at 4.4 Gy/fraction. At BED of 100 Gy, "good" cosmesis was more frequently observed in patients receiving BT, 95% (95% CI: 88-100%) vs 79% (95% CI: 60-82%), p < 0.05. Similar results were found for "good" cosmesis at BED >100 Gy. No difference in "poor" cosmesis was noted at any BED. LR was <7% for both at one year.
CONCLUSION
BT has favorable cosmesis over EBRT for skin SCCs/BCCs at common fractionation regimens. Prospective studies comparing EBRT vs BT are warranted.
Topics: Aged; Brachytherapy; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dose Fractionation, Radiation; Humans; Radiotherapy Dosage; Skin Neoplasms
PubMed: 29370985
DOI: 10.1016/j.radonc.2017.12.029 -
World Journal of Clinical Cases Nov 2021Previous studies had shown endoscopic retrograde appendicitis therapy (ERAT) is an effective treatment for acute appendicitis. However, different studies reported...
BACKGROUND
Previous studies had shown endoscopic retrograde appendicitis therapy (ERAT) is an effective treatment for acute appendicitis. However, different studies reported conflicting outcomes regarding the effectiveness of ERAT in comparison with laparoscopic appendectomy (LA).
AIM
To compare the effectiveness of ERAT with LA.
METHODS
Randomized controlled trials (RCTs) and retrospective studies of ERAT for acute uncomplicated appendicitis were searched in PubMed, Cochrane Library, Web of Science, Embase database, China National Knowledge Infrastructure (CNKI), the WanFang Database, and Chinese Scientific Journals Database (VIP) from the establishment date to March 1 2021. Heterogeneity was assessed using the I-squared statistic. Pooled odds ratios (OR), weighted mean difference (WMD), and standard mean difference (SMD), with 95% confidence intervals (CI) were calculated through either fixed-effects or random-effects model. Sensitivity analysis was also performed. Publication bias was tested by Egger's test, and Begg's test. The quality of included RCT were evaluated by the Jadad scale, while Newcastle-Ottawa scale is adopted for assessing the methodological quality of case-control studies. All statistical analysis was performed using Stata 15.1 statistical software. All statistical analysis was performed using Stata 15.1 statistical software. This study is registered with PROSPERO, CRD42021243955.
RESULTS
After screening, 10 RCTs and 2 case-control studies were included in the current systematic review. Firstly, the length of hospitalizations [WMD = -1.15, 95%CI: -1.99, -0.31; = 0.007] was shorter than LA group. Secondly, the level of post-operative CRP [WMD = -10.06, 95%CI: (-17.39, -2.73); = 0.007], TNF-α [WMD = -7.70, 95%CI: (-8.47, -6.93); 0.001], and IL-6 Levels [WMD = -9.78, 95%CI: (-10.69, -8.88); 0.001; 0.001] in ERAT group was significantly lower than LA group. Thirdly, ERAT group had a lower incidence of intestinal obstruction than LA group. [OR = 0.19, 95%CI: (0.05, 0.79); = 0.020]. Moreover, the quality of 10 RCTs were low with 0-3 Jadad scores, while the methodological quality of two case-control studies were fair with a score of 2 (each).
CONCLUSION
Compared with LA, ERAT reduces operation time, the level of postoperative inflammation, and results in fewer complications and shorter recovery time, with preserving the appendix and its immune and biological functions.
PubMed: 34904091
DOI: 10.12998/wjcc.v9.i33.10208 -
Cytokine Jan 2021COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea...
BACKGROUND
COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered.
METHODOLOGY
The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results.
RESULTS
Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)).
CONCLUSION
Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.
Topics: COVID-19; Cytokines; Humans; Low-Level Light Therapy; Lung; Macrophages; Neutrophils; Pneumonia; PubMed; Pulmonary Edema; Reactive Oxygen Species; Respiratory Distress Syndrome
PubMed: 33128927
DOI: 10.1016/j.cyto.2020.155312 -
JAMA Dermatology Mar 2019Dermatofibrosarcoma protuberans (DFSP) has the potential for local destruction and recurrence, although it carries a low risk of metastasis. Complete surgical resection...
IMPORTANCE
Dermatofibrosarcoma protuberans (DFSP) has the potential for local destruction and recurrence, although it carries a low risk of metastasis. Complete surgical resection with negative margins is considered the gold standard for treatment; however, there are cases that are unresectable owing to tumor extension or size or owing to risk of cosmetic and/or functional impairment. Imatinib treatment has been used for locally advanced or metastatic DFSP.
OBJECTIVE
To evaluate the usefulness of imatinib for treating DFSP.
EVIDENCE REVIEW
We conducted a systematic review on the PubMed and Embase databases for articles published from September 2002 through October 2017 using the key words "dermatofibrosarcoma" or "dermatofibrosarcoma protuberans" AND "therapy" AND "imatinib." References within retrieved articles were also reviewed to identify additional studies. Studies of adults with histologically proven DFSP treated with imatinib as monotherapy or as an adjuvant or neoadjuvant therapy to surgery were included. Extracted data were analyzed using descriptive statistics. PRISMA guidelines were followed. All analysis took place October through December 2017.
FINDINGS
Nine studies met inclusion criteria; 152 patients were included. The calculated mean patient age was 49.3 years (range, 20-73 years). Calculated mean tumor diameter was 9.9 cm (range, 1.2-49.0 cm). When COL1A1-PDGFβ protein translocation (collagen, type 1, alpha 1-platelet-derived growth factor β) was reported, it was present in 90.9% of patients (111 of 122). Complete response was seen in 5.2% of patients (8 of 152), partial response in 55.2% (84 of 152), stable disease in 27.6% (42 of 152), and progression in 9.2% (14 of 152). Four of the 152 patients (2.6%) were excluded from the analysis owing to unknown or unevaluable response. There were no differences in response rate using 400-mg or 800-mg daily doses (67.5% or 27 of 40 patients for 400-mg dose vs 67.1% or 49 of 73 patients for 800-mg dose complete or partial response; P > .99). Adverse events were present in at least 73.5% of cases (78 of 106); severe adverse events were present in 15.1% of cases (20 of 132).
CONCLUSIONS AND RELEVANCE
Imatinib is a useful directed therapy in patients with DFSP who are not surgical candidates owing to disease extension or significant cosmetic or functional impairment. There seems to be no difference between 400- or 800-mg daily doses.
Topics: Adult; Aged; Dermatofibrosarcoma; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Imatinib Mesylate; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Skin Neoplasms; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 30601909
DOI: 10.1001/jamadermatol.2018.4940 -
Brachytherapy 2021The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of...
PURPOSE
The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer.
METHODS AND MATERIALS
The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life.
RESULTS
LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure.
CONCLUSIONS
LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.
Topics: Androgen Antagonists; Brachytherapy; Consensus; Humans; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Retrospective Studies
PubMed: 34509378
DOI: 10.1016/j.brachy.2021.07.006