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Seminars in Arthritis and Rheumatism Feb 2023To identify reports of colchicine-induced neuropathy and myopathy and ascertain risk factors associated with this toxicity at commonly used doses.
OBJECTIVE
To identify reports of colchicine-induced neuropathy and myopathy and ascertain risk factors associated with this toxicity at commonly used doses.
METHODS
A systematic review of case reports was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA methodology). PubMed and EMBASE were searched through October 2021 for case reports of neuropathy and/or myopathy associated with the use of colchicine at therapeutic doses.
RESULTS
A total of 143 cases of neuromyopathy from 99 articles were identified as having a "definite" or "probable" association with colchicine usage, as assessed by the Naranjo algorithm. Most of these cases presented with features of both neuropathy and myopathy (n=72, 51%) but symptoms of myopathy were predominant. The mean total daily dose was 1.25±0.60 mg and 48% had been taking colchicine for more than 12 months before presenting with neuromyopathy. A total of 117 (82%) of all reports had either a significant co-morbidity or possible colchicine drug-drug interaction, while 57 (40%) had both risk factors. A total of 26 cases (18%) had no significant risk factor but only 15 of these reports contained complete descriptions of the patient's co-morbidities and co-medications. Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days. There were 3 deaths reported which were due to multi-organ failure despite cessation of colchicine and medical management. Colchicine was restarted at reduced doses in 15 cases and 73% had no symptom recurrence.
CONCLUSION
Neuromyopathy is an uncommon but reported adverse effect of colchicine. Cases generally present with proximal myopathy symptoms. Cases of colchicine neuromyopathy are largely reported in patients on commonly used doses. Renal and hepatic dysfunction and medications that inhibit cytochrome P450 3A4 isozyme (CYP3A4) and P-glycoprotein (P-gp) appear to be the most significant risk factors. Fortunately, cessation of colchicine generally leads to complete resolution of symptoms. Recommencement of colchicine at reduced doses appeared to be usually safe.
Topics: Humans; Colchicine; Neuromuscular Diseases; Muscular Diseases; Peripheral Nervous System Diseases; Risk Factors
PubMed: 36512928
DOI: 10.1016/j.semarthrit.2022.152150 -
Life (Basel, Switzerland) Apr 2022Introduction: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. This meta-analysis compared local steroid injections (LSIs) versus carpal tunnel... (Review)
Review
Introduction: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. This meta-analysis compared local steroid injections (LSIs) versus carpal tunnel release (CTR) for the management of CTS. Neurophysiological parameters, patient-reported outcome measures (PROMs), and the complication rate were investigated. We hypothesized that LSIs may represent an effective and safe alternative to surgical management. Methods: This systematic review was conducted according to the 2020 PRISMA statement. All the clinical investigations comparing LSIs versus CTR for carpal tunnel syndrome were accessed. In March 2022, the following databases were accessed: Pubmed, Web of Science, Google Scholar, and Embase. No time constrains were used for the search. The risk of bias and statistical analyses were conducted using the Review Manager Software 5.3 (The Nordic Cochrane Collaboration, Copenhagen). Results: Data from 1096 procedures were retrieved. The mean follow-up was 12.3 (1 to 58) months. The mean age of the patients was 51.1 ± 4.6. Nocturnal paraesthesia (p < 0.0001) and visual analogue scale (p < 0.0001) were greater in the LSIs cohort. No difference was found in the functional (p = 0.2) and symptom (p = 0.4) subscales of the Boston Carpal Tunnel Questionnaire (BCTQ), median nerve distal motor latency (p = 0.9), median nerve motor amplitude (p = 0.7), median nerve sensory conduction velocity (p = 0.4), or median nerve sensory amplitude (p = 0.3). No difference was found in terms of minor complications (p = 0.9). No major complications were observed within the duration of follow-up. Conclusion: Both CTR and LSIs were effective and feasible in reducing symptoms of carpal tunnel syndrome. Though LSIs led to greater pain relief, this superiority was not permanent. Irrespective of the severity of the symptoms, current evidence suggests that a cycle of LSIs may be considered in patients with CTS. However, patients must be aware that LSIs may not be the definitive therapy, and CTR should be recommended.
PubMed: 35455023
DOI: 10.3390/life12040533 -
Acta Neurologica Belgica Dec 2022Coronavirus disease 2019 (COVID-19) is responsible for a wide variety of multi-system clinical features. Facial nerve palsy (FNP) is identified as one of the... (Review)
Review
BACKGROUND
Coronavirus disease 2019 (COVID-19) is responsible for a wide variety of multi-system clinical features. Facial nerve palsy (FNP) is identified as one of the neurological complications of the virus. This work aims to systematically review the clinical picture, laboratory/imaging findings, treatment options, and prognostic factors of FNP in COVID-19 patients.
METHODS
Using six online databases, a search was conducted to include all articles with patients infected with COVID-19 and presenting with unilateral or bilateral FNP. Screening for eligibility and data extraction were done by three and four independent reviewers, respectively. Descriptive analyses and data visualizations were done using Google Sheets. Survival analysis and Kaplan-Meier plotting were done by R software.
RESULTS
The data from 22 studies included 32 patients who were infected with COVID-19 and presented with clinical features of FNP. Fourteen patients were male while 18 were female. FNP affected 29 patients unilaterally and 3 patients bilaterally. The imaging findings confirmed that complications of FNP were COVID-19 related. Additionally, antivirals combined with steroids had the lowest median time (21, IQR = 8) to clinical improvement compared to steroid-only (30, IQR = 15) and antiviral-only (33, IQR = 3.5) treatments.
CONCLUSION
This study has shown a potential correlation between the increased incidence of FNP and COVID-19. We have also found that combining antivirals with steroids may have better outcomes in patients with FNP and COVID-19 although the evidence to support this claim is not strong enough. Further studies are required to assess the extent of linkage between the two conditions and how to properly manage FNP when encountered in COVID-19 patients.
Topics: Humans; Male; Female; COVID-19; Facial Nerve; Retrospective Studies; Bell Palsy; Facial Paralysis; Antiviral Agents
PubMed: 35917018
DOI: 10.1007/s13760-022-02026-8 -
The Cochrane Database of Systematic... Nov 2023Macular holes cause severe impairment of sight. With the aim of improving the outcome of surgery for macular holes, particularly larger macular holes (those measuring... (Review)
Review
BACKGROUND
Macular holes cause severe impairment of sight. With the aim of improving the outcome of surgery for macular holes, particularly larger macular holes (those measuring over 400 μm), a variable period of face-down positioning may be advised. This review is an update of a Cochrane Review published in 2011.
OBJECTIVES
To evaluate the effect of postoperative face-down positioning on the outcome of surgery for macular hole.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 5), which contains the Cochrane Eyes and Vision Trials Register, Ovid MEDLINE, Ovid Embase, the ISRCTN registry, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 25 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which postoperative face-down positioning was compared to no face-down positioning following surgery for macular holes. The primary outcome of interest was closure of the macular hole. Other outcomes of interest included visual outcomes, quality of life outcomes, and the occurrence of adverse events. Pairs of review authors independently selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We analysed dichotomous data as risk ratios (RRs), and continuous data as mean differences (MDs), with 95% confidence intervals (CI). The unit of analysis was eyes.
MAIN RESULTS
We included eight studies allocating a total of 709 eyes (699 participants). There was heterogeneity in study design, including the control group treatment (from no positioning to strict maintenance of other 'face-forward' postures) and surgical procedures (with or without inner limiting membrane peeling, with or without cataract surgery). There were also different durations of positioning, with two studies using 3 days, two studies using 5 days, and three studies using 10 days of face-down positioning. Whilst the overall risk of bias was low, all included studies were judged to be at high or unclear risk of bias due to absence of assessment of adherence to the 'prescribed' intervention of face-down positioning or posturing. The primary outcome of successful anatomical hole closure at one to six months following surgery was reported in 95 of every 100 eyes of participants advised to position face-down for at least three days after surgery, and in 85 of every 100 eyes of participants not advised to position face-down (RR 1.05, 95% CI 0.99 to 1.12, 709 eyes, 8 studies, I² = 44%). Amongst the 327 eyes of participants with macular holes of at least 400 μm, hole closure was noted in 94 of every 100 eyes of participants advised to position face-down, and in 84 of every 100 eyes of participants not advised to position face-down (RR 1.08, 95% CI 0.93 to 1.26, 5 studies, I² = 62%). Amongst the 129 eyes of participants with macular holes of less than 400 μm, hole closure was noted in 100 of every 100 eyes of participants advised to position face-down, and in 96 of every 100 eyes of participants not advised to position face-down (RR 1.03, CI 0.97 to 1.11, 4 studies, I² = 0%). The certainty of the evidence was low, downgraded for imprecision (CIs including no effect) and study design limitations (with different durations of face-down posturing used in the absence of a dose-response gradient, and limitations in measuring the exposure). Meta-analysis of visual acuity data was challenging given the use of different definitions of postoperative visual outcome across studies. Three studies reported findings by gain in Early Treatment Diabetic Retinopathy Study (ETDRS) letters (MD 2.04, 95% CI -0.01 to 4.09, very low-certainty evidence). Meta-analyses of quality of life data were not possible because of inconsistency in outcome metrics across studies. One study reported no difference between groups in quality of life, as reported on a validated quality of life metric scale (the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25), between face-down positioning for five days and non-face-down positioning (median NEI VFQ-25 score was 89 (interquartile range (IQR) 76 to 94) in the face-down group versus 87 (IQR 73 to 93) in the non-face-down group (adjusted mean difference on a logistic scale 0.02, 95% CI -0.03 to 0.07, P = 0.41)). Two studies reported increased ease of positioning and less pain in non-face-down positioning groups on non-validated 0-to-10-point visual analogue scores. On an ease-of-positioning score running from 0 (very difficult) to 10 (very easy), there were consistent reports of the discomfort associated with face-down positioning: the median participant-reported ease-of-positioning score was 6 (IQR 4 to 8) in those undergoing 5 days of face-down positioning versus 9 (IQR 7 to 10) in the comparator group (P = 0.01). On a pain score with 0 being pain-free and 10 being in severe pain, mean pain score was 6.52 ± 2.48 in the face-down positioning group versus 2.53 ± 2.6 in the non-face-down positioning group. The adverse event of postoperative nerve compression occurred in less than 1 in every 100 (3 per 1000) participants advised to position face-down, and 0 in every 100 participants not advised to position face-down (699 participants, 8 studies, moderate-certainty evidence).
AUTHORS' CONCLUSIONS
We identified eight RCTs evaluating face-down positioning following surgery for macular hole. The included studies were not all directly comparable due to differences in the surgical techniques used and the durations of postoperative positioning advised. Low-certainty evidence suggests that face-down positioning may have little or no effect on macular hole closure after surgery. Face-down positioning is a low-risk intervention, with serious adverse events affecting fewer than 1 in 300 people. We suggest that any future trials focus on patients with larger macular holes, with interventions and outcome measures used in previous trials (i.e. with inner limiting membrane peeling, positioning durations of three to five days, and validated quality of life metrics) to allow future meta-analyses to determine any effect with greater precision and confidence.
Topics: Humans; Cataract Extraction; Diabetic Retinopathy; Pain; Retinal Perforations
PubMed: 37987517
DOI: 10.1002/14651858.CD008228.pub3 -
Acta Neurologica Scandinavica Nov 2020A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies...
A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS.
Topics: Adult; Central Nervous System; Efferent Pathways; Evoked Potentials, Motor; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Neural Conduction; Peripheral Nervous System
PubMed: 32474916
DOI: 10.1111/ane.13289 -
Journal of Clinical Medicine Nov 2023Carpal tunnel syndrome (CTS) is the most common entrapment syndrome, primarily affecting women between the ages of 40 and 70, and conservative treatments are the first... (Review)
Review
BACKGROUND
Carpal tunnel syndrome (CTS) is the most common entrapment syndrome, primarily affecting women between the ages of 40 and 70, and conservative treatments are the first option for mild-to-moderate CTS. However, the comparisons between extracorporeal shock wave therapy (ESWT) and other non-surgical methods in the treatment of mild-to-moderate CTS remain controversial, and an updated systematic review is needed.
METHODS
An electronic search was performed, and all available articles until August 2023 were included in the analysis. The overall quality of evidence was assessed by the GRADE approach. Meta-analyses were conducted using Manager V.5.3.3. Pooled effect sizes were expressed as the weighted mean difference (WMD) with 95% confidence intervals (CIs).
RESULTS
A total of 19 RCTs were included. Low-level quality evidence showed that ESWT outperformed the control intervention in terms of functional improvements, pain relief, electrodiagnostic parameters, and cross-sectional area of the median nerve at any time point of follow-up. Compared to local corticosteroid injection (LCI), there were statistically better improvements in functional improvements, pain relief, and electrodiagnostic parameters at 3 and 6 months of follow-up.
CONCLUSIONS
There is low-level quality evidence to show that both fESWT and rESWT are more clinically effective than controls in symptom relief, functional enhancement, and electrophysiologic parameters' improvement for patients with mild-to-moderate CTS at any time point of follow-up. Compared with LCI, ESWT yielded similar short-term (<1 month) but better medium- (1-6 months) and long-term (>6 months) improvements in pain relief and functional recovery with fewer potential complications.
PubMed: 38068415
DOI: 10.3390/jcm12237363 -
Physiotherapy Sep 2023The upper limb neurodynamic test for median nerve (ULNT1) is commonly applied for assessment of cervical radiculopathy (CR). However, the diagnostic accuracy of ULNT1 in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The upper limb neurodynamic test for median nerve (ULNT1) is commonly applied for assessment of cervical radiculopathy (CR). However, the diagnostic accuracy of ULNT1 in diagnosing CR remains unclear.
OBJECTIVE
This study aimed to examine the diagnostic accuracy of the ULNT1 for the CR.
DATA SOURCES
Four databases were searched for relevant studies published up to April 30, 2023.
STUDY SELECTION
Cross-sectional or cohort studies that assessed the diagnostic accuracy of ULNT1 for CR were included.
DATA SYNTHESIS
The methodological quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. A bivariate random-effects regression model was used for the data synthesis. The overall quality of evidence was evaluated using the GRADE approach.
RESULTS
A total of 592 references were identified, and five studies with 465 patients met the inclusion criteria. The overall quality of the body of evidence was very low across studies. Heterogeneity of studies was high. The pooled sensitivity and specificity of the ULNT1 were 0.69 (95% CI 0.50-0.83) and 0.54 (95% CI 0.36-0.71), respectively. The summary receiver operating characteristic curve area was 0.65 (95% CI 0.61-0.69).
CONCLUSION
There is low certainty of evidence that the ULNT1 has only fair accuracy in diagnosing CR. The ULNT1 was recommended as an add-on test after the existing diagnostic pathway to enhance diagnostic accuracy further. High-quality studies which follow the Standards for Reporting of Diagnostic Accuracy and the QUADAS-2; a revised tool for the quality assessment of diagnostic accuracy, are needed.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO: CRD42021255686 CONTRIBUTION OF THE PAPER.
Topics: Humans; Cross-Sectional Studies; Radiculopathy; Sensitivity and Specificity; ROC Curve; Upper Extremity
PubMed: 37356367
DOI: 10.1016/j.physio.2023.06.001 -
Hand (New York, N.Y.) Jan 2023Magnetic resonance diffusion tensor imaging (DTI) can detect microstructural changes in peripheral nerves. Studies have reported that the median nerve apparent diffusion... (Meta-Analysis)
Meta-Analysis Review
Magnetic resonance diffusion tensor imaging (DTI) can detect microstructural changes in peripheral nerves. Studies have reported that the median nerve apparent diffusion coefficient (ADC), a quantification of water molecule diffusion direction, is sensitive in diagnosing carpal tunnel syndrome (CTS). Five databases were searched for studies using ADC to investigate CTS. Apparent diffusion coefficient (measured in mm/s) were pooled in random-effects meta-analyses. Twenty-two studies met criteria yielding 592 patients with CTS and 414 controls. Median nerve ADC were measured at the level of the distal radioulnar joint (CTS ADC: 1.11, 95% CI: 1.07-1.15, I = 54%; control ADC: 1.04, 95% CI: 1.01-1.07, I = 57%), pisiform (CTS ADC: 1.39, 95% CI: 1.37-1.42, I = 0%; control ADC: 1.27, 95% CI: 1.23-1.31, I = 59%), hamate (CTS ADC: 1.40, 95% CI: 1.36-1.43, I = 58%; control ADC: 1.27, 95% CI: 1.25-1.28, I = 47%), and as an combination of several measurements (CTS ADC: 1.40, 95% CI: 1.37-1.47, I = 100%; control ADC: 1.39, 95% CI: 1.24-1.53, I = 100%). Median nerve ADC is decreased in individuals with CTS compared to controls at the levels of the hamate and pisiform. ADC cut-offs to diagnose CTS should be established according to these anatomic levels and can be improved through additional studies that include use of a wrist coil.
Topics: Humans; Carpal Tunnel Syndrome; Diffusion Tensor Imaging; Median Nerve; Magnetic Resonance Imaging; Wrist Joint
PubMed: 35695339
DOI: 10.1177/15589447221096706 -
Pediatrics Dec 2021Peripheral nerve injuries in children can result in devastating lifelong deficits. Because of the time-sensitive nature of muscle viability and the limited speed of...
Peripheral nerve injuries in children can result in devastating lifelong deficits. Because of the time-sensitive nature of muscle viability and the limited speed of nerve regeneration, early recognition and treatment of nerve injuries are essential to restore function. Innovative surgical techniques have been developed to combat the regenerative length and speed; these include nerve transfers. Nerve transfers involve transferring a healthy, expendable donor nerve to an injured nerve to restore movement and sensation. Nerve transfers are frequently used to treat children affected by conditions, including UE trauma, brachial plexus birth injury, and acute flaccid myelitis. Pediatricians play an important role in the outcomes of children with these conditions through early diagnosis and timely referrals. With this review, we aim to provide awareness of state-of-the-art surgical treatment options that significantly improve the function of children with traumatic nerve injuries, brachial plexus birth injury, and acute flaccid myelitis.
Topics: Child; Compartment Syndromes; Forearm Injuries; Humans; Humeral Fractures; Median Nerve; Myelitis; Neonatal Brachial Plexus Palsy; Nerve Regeneration; Nerve Transfer; Neurosurgical Procedures; Peripheral Nerve Injuries; Peripheral Nerves; Radial Nerve; Plastic Surgery Procedures; Recovery of Function; Time Factors; Ulnar Nerve
PubMed: 34851416
DOI: 10.1542/peds.2021-052556 -
The Cochrane Database of Systematic... Jul 2021Chordoma is a rare primary bone tumour with a high propensity for local recurrence. Surgical resection is the mainstay of treatment, but complete resection is often... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chordoma is a rare primary bone tumour with a high propensity for local recurrence. Surgical resection is the mainstay of treatment, but complete resection is often morbid due to tumour location. Similarly, the dose of radiotherapy (RT) that surrounding healthy organs can tolerate is frequently below that required to provide effective tumour control. Therefore, clinicians have investigated different radiation delivery techniques, often in combination with surgery, aimed to improve the therapeutic ratio.
OBJECTIVES
To assess the effects and toxicity of proton and photon adjuvant radiotherapy (RT) in people with biopsy-confirmed chordoma.
SEARCH METHODS
We searched CENTRAL (2021, Issue 4); MEDLINE Ovid (1946 to April 2021); Embase Ovid (1980 to April 2021) and online registers of clinical trials, and abstracts of scientific meetings up until April 2021.
SELECTION CRITERIA
We included adults with pathologically confirmed primary chordoma, who were irradiated with curative intent, with protons or photons in the form of fractionated RT, SRS (stereotactic radiosurgery), SBRT (stereotactic body radiotherapy), or IMRT (intensity modulated radiation therapy). We limited analysis to studies that included outcomes of participants treated with both protons and photons.
DATA COLLECTION AND ANALYSIS
The primary outcomes were local control, mortality, recurrence, and treatment-related toxicity. We followed current standard Cochrane methodological procedures for data extraction, management, and analysis. We used the ROBINS-I tool to assess risk of bias, and GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included six observational studies with 187 adult participants. We judged all studies to be at high risk of bias. Four studies were included in meta-analysis. We are uncertain if proton compared to photon therapy worsens or has no effect on local control (hazard ratio (HR) 5.34, 95% confidence interval (CI) 0.66 to 43.43; 2 observational studies, 39 participants; very low-certainty evidence). Median survival time ranged between 45.5 months and 66 months. We are uncertain if proton compared to photon therapy reduces or has no effect on mortality (HR 0.44, 95% CI 0.13 to 1.57; 4 observational studies, 65 participants; very low-certainty evidence). Median recurrence-free survival ranged between 3 and 10 years. We are uncertain whether proton compared to photon therapy reduces or has no effect on recurrence (HR 0.34, 95% CI 0.10 to 1.17; 4 observational studies, 94 participants; very low-certainty evidence). One study assessed treatment-related toxicity and reported that four participants on proton therapy developed radiation-induced necrosis in the temporal bone, radiation-induced damage to the brainstem, and chronic mastoiditis; one participant on photon therapy developed hearing loss, worsening of the seventh cranial nerve paresis, and ulcerative keratitis (risk ratio (RR) 1.28, 95% CI 0.17 to 9.86; 1 observational study, 33 participants; very low-certainty evidence). There is no evidence that protons led to reduced toxicity. There is very low-certainty evidence to show an advantage for proton therapy in comparison to photon therapy with respect to local control, mortality, recurrence, and treatment related toxicity.
AUTHORS' CONCLUSIONS
There is a lack of published evidence to confirm a clinical difference in effect with either proton or photon therapy for the treatment of chordoma. As radiation techniques evolve, multi-institutional data should be collected prospectively and published, to help identify persons that would most benefit from the available radiation treatment techniques.
Topics: Adult; Bias; Bone Neoplasms; Chordoma; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Observational Studies as Topic; Photons; Progression-Free Survival; Proton Therapy; Radiosurgery; Radiotherapy, Adjuvant; Radiotherapy, Intensity-Modulated; Time Factors
PubMed: 34196007
DOI: 10.1002/14651858.CD013224.pub2