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Health Technology Assessment... Dec 2023A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.
OBJECTIVE
To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
REVIEW METHODS
Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research.
RESULTS
Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified ( ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included ( = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials.
LIMITATIONS
Many studies were small and of poor quality. No comparative studies were found for some therapies.
CONCLUSIONS
The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection.
STUDY REGISTRATION
PROSPERO CRD42020221357.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in ; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Carcinoma, Hepatocellular; Ethanol; Liver Neoplasms; Network Meta-Analysis; Prospective Studies; Randomized Controlled Trials as Topic; Ablation Techniques
PubMed: 38149643
DOI: 10.3310/GK5221 -
Surgical and Radiologic Anatomy : SRA Mar 2024Endoscopic third ventriculostomy (ETV) is a surgical procedure that can lead to complications and requires detailed preoperative planning. This study aimed to provide a...
PURPOSE
Endoscopic third ventriculostomy (ETV) is a surgical procedure that can lead to complications and requires detailed preoperative planning. This study aimed to provide a more accurate understanding of the anatomy of the third ventricle and the location of important structures to improve the safety and success of ETV.
METHODS
We measured the stereotactic coordinates of six points of interest relative to a predefined stereotactic reference point in 23 cadaver brain hemi-sections, 200 normal brain magnetic resonance imaging (MRI) scans, and 24 hydrocephalic brain MRI scans. The measurements were statistically analyzed, and comparisons were made.
RESULTS
We found some statistically significant differences between genders in MRIs from healthy subjects. We also found statistically significant differences between MRIs from healthy subjects and both cadaver brains and MRIs with hydrocephalus, though their magnitude is very small and not clinically relevant. Some stereotactic points were more posteriorly and inferiorly located in cadaver brains, particularly the infundibular recess and the basilar artery. It was found that all stereotactic points studied were more posteriorly located in brains with hydrocephalus.
CONCLUSION
The study describes periventricular structures in cadaver brains and MRI scans from healthy and hydrocephalic subjects, which can guide neurosurgeons in planning surgical approaches to the third ventricle. Overall, the study contributes to understanding ETV and provides insights for improving its safety and efficacy. The findings also support that practicing on cadaveric brains can still provide valuable information and is valid for study and training of neurosurgeons unfamiliar with the ETV technique.
Topics: Humans; Male; Female; Third Ventricle; Neuroendoscopy; Brain; Hydrocephalus; Ventriculostomy; Cadaver; Treatment Outcome; Retrospective Studies
PubMed: 38374441
DOI: 10.1007/s00276-024-03312-1 -
Operative Neurosurgery (Hagerstown, Md.) Aug 2023Stereotactic neurosurgical brain biopsies are afflicted with risks of inconclusive results and hemorrhage. Such complications can necessitate repeated trajectories and...
BACKGROUND
Stereotactic neurosurgical brain biopsies are afflicted with risks of inconclusive results and hemorrhage. Such complications can necessitate repeated trajectories and prolong surgical time.
OBJECTIVE
To develop and introduce a 1-insertion stereotactic biopsy kit with direct intraoperative optical feedback and to evaluate its applicability in 3 clinical cases.
METHODS
An in-house forward-looking probe with optical fibers was designed to fit the outer cannula of a side-cutting biopsy kit. A small aperture was made at the tip of the outer cannula and the edges aligned with the optical probe inside. Stereotactic biopsies were performed using the Leksell Stereotactic System. Optical signals were measured in millimeter steps along the preplanned trajectory during the insertion. At the region with the highest 5-aminolevulinic acid (5-ALA)-induced fluorescence, the probe was replaced by the inner cannula, and tissue samples were taken. The waiting time for pathology diagnosis was noted.
RESULTS
Measurements took 5 to 10 minutes, and the surgeon received direct visual feedback of intraoperative 5-ALA fluorescence, microcirculation, and tissue gray-whiteness. The 5-ALA fluorescence corroborated with the pathological findings which had waiting times of 45, 50, and 75 minutes. Because only 1 trajectory was required and the patient could be prepared for the end of surgery immediately after sampling, this shortened the total surgical time.
CONCLUSION
A 1-insertion stereotactic biopsy procedure with real-time optical guidance has been presented and successfully evaluated in 3 clinical cases. The method can be modified for frameless navigation and thus has great potential to improve safety and diagnostic yield for both frameless and frame-based neurosurgical biopsy procedures.
Topics: Humans; Stereotaxic Techniques; Brain Neoplasms; Biopsy; Neurosurgical Procedures; Aminolevulinic Acid; Brain
PubMed: 37083519
DOI: 10.1227/ons.0000000000000722 -
Radiotherapy and Oncology : Journal of... Sep 2023Although the effects of estimated dose of radiation to immune cells (EDRIC) in stage III NSCLC, LA-NSCLC, LS-SCLC and esophageal cancer on clinical outcomes have been...
Impact of radiation dose to the immune system on disease progression and survival for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.
OBJECTIVES
Although the effects of estimated dose of radiation to immune cells (EDRIC) in stage III NSCLC, LA-NSCLC, LS-SCLC and esophageal cancer on clinical outcomes have been studied, its impact in early-stage non-small cell lung cancer (ES-NSCLC) is unknown. In this study, we evaluated the role of EDRIC and identified the factors influencing EDRIC in this population.
METHODS AND MATERIALS
We retrospectively analyzed 211 pathologically confirmed ES-NSCLC patients who were treated with SBRT between 2007 and 2020. EDRIC was calculated based on the model developed by Jin et al. and improved by Ladbury et al. Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate CSS, PFS, LPFS, and DMFS. Pearson correlation was used to assess the correlation between variables. We further validated our findings in an independent cohort of 119 patients with ES-NSCLC.
RESULTS
A total of 211 patients were included with median follow-up of 48 months in the training cohort. The median EDRIC was 2.178 Gy (range: 0.426-6.015). GTV showed a positive correlation with EDRIC (r = 0.707, P = 0.000). In multivariate analysis, higher EDRIC was significantly associated with worse CSS (HR = 1.468, P = 0.009) and DMFS (HR = 1.491, P = 0.016). Considering each EDRIC quartile, there was a significant difference in CSS between 1st and 4th and 1st and 3rd quartile (P = 0.000, P = 0.004, respectively); and DMFS between 1st and 4th,1st and 3rd, and 1st and 2nd quartile (P = 0.000, P = 0.000, P = 0.008, respectively). In the subgroup and validation cohort, EDRIC was also the important prognostic predictor of CSS and DMFS using multivariate analysis.
CONCLUSION
EDRIC was an independent predictor of CSS and DMFS in ES-NSCLC, and it was affected by GTV and tumor location. Though EDRIC is a critical determinant of treatment outcomes, it is quantifiable and potentially modifiable. Additional researches exploring the feasibility of achieving lower EDRIC while maintaining adequate tumor coverage during radiotherapy are warranted.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome; Small Cell Lung Carcinoma; Immune System; Disease Progression; Radiation Dosage
PubMed: 37437605
DOI: 10.1016/j.radonc.2023.109804 -
Current Opinion in Urology Jul 2024Oligometastatic tumors illustrate a distinct state between localized and systematic disease and might harbor unique biologic features. Moreover, these tumors represent a... (Review)
Review
PURPOSE OF REVIEW
Oligometastatic tumors illustrate a distinct state between localized and systematic disease and might harbor unique biologic features. Moreover, these tumors represent a different clinical entity, with a potential of long-term disease control or even cure, therefore they receive growing attention in the field of urologic oncology.
RECENT FINDINGS
Currently, there is no consensus on the definition of oligometastatic prostate cancer, most experts limit it to a maximum of three to five lesions and involvement of no more than two organs, excluding visceral metastases. Quality data on oligometastatic bladder cancer is scarce, however, a consensus of experts defined it as a maximum of three metastatic lesions, either resectable or suitable for stereotactic therapy, without restrictions to the number of organs involved. As for kidney cancer, a maximum number of five metastases, without limitations to the location are defined as oligometastatic, with an important implication of timing of developing metastases since diagnosis of the primary tumor.
SUMMARY
Defining oligometastatic state among urological tumors reflecting their distinct biological and clinical behavior is crucial to establish a sound framework for future clinical trials, and to facilitate guideline and policy formulation for improved patient care. Advancements in molecular imaging are expected to transform the field of oligometastatic urologic tumors in the future.
Topics: Humans; Neoplasm Metastasis; Male; Urinary Bladder Neoplasms; Kidney Neoplasms; Prostatic Neoplasms; Urologic Neoplasms
PubMed: 38704827
DOI: 10.1097/MOU.0000000000001184 -
Radiotherapy and Oncology : Journal of... Dec 2023Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both...
BACKGROUND AND PURPOSE
Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both efficacy and toxicity. This manuscript characterizes factors associated with intracranial control and radiation necrosis in this group.
MATERIALS AND METHODS
All patients had non-small cell lung cancer, renal cell carcinoma, or melanoma and were treated from 2013 to 2021 at two institutions with ICI and SRS/SRT. Univariate and multivariate analysis were used to analyze factors associated with local failure (LF) and grade 2+ (G2 + ) radiation necrosis.
RESULTS
There were 179 patients with 549 metastases. The median follow up from SRS/SRT was 14.7 months and the median tumor size was 7 mm (46 tumors ≥ 20 mm). Rates of LF and G2 + radiation necrosis per metastasis were 5.8% (32/549) and 6.9% (38/549), respectively. LF rates for ICI +/- 1 month from time of radiation versus not were 3% (8/264) and 8% (24/285) (p = 0.01), respectively. G2 + radiation necrosis rates for PD-L1 ≥ 50% versus < 50% were 17% (11/65) and 3% (5/203) (p=<0.001), respectively. PD-L1 ≥ 50% remained significantly associated with G2 + radiation necrosis on multivariate analysis (p = 0.03). Rates of intracranial failure were 54% (80/147) and 17% (4/23) (p = 0.001) for those without and with G2 + radiation necrosis, respectively.
CONCLUSIONS
PD-L1 expression (≥50%) may be associated with higher rates of G2 + radiation necrosis, and there may be improved intracranial control following the development of radiation necrosis. Administration of ICIs with SRS/SRT is overall safe, and there may be some local control benefit to delivering these concurrently.
Topics: Humans; Radiosurgery; Immune Checkpoint Inhibitors; Carcinoma, Non-Small-Cell Lung; B7-H1 Antigen; Lung Neoplasms; Brain Neoplasms; Radiation Injuries; Kidney Neoplasms; Necrosis; Retrospective Studies
PubMed: 37769968
DOI: 10.1016/j.radonc.2023.109920 -
BMJ Case Reports Jul 2023A man in his 70s previously diagnosed with an adenocarcinoma of the prostate, received external beam radiation therapy (EBRT) and brachytherapy 11 years ago. Ten years...
A man in his 70s previously diagnosed with an adenocarcinoma of the prostate, received external beam radiation therapy (EBRT) and brachytherapy 11 years ago. Ten years later, he developed urinary symptoms and a cystoscopy identified a bladder neck tumour. A transurethral resection of a bladder tumour was performed, and pathology revealed a high-grade adenocarcinoma consistent with a colorectal primary. A colonoscopy was unremarkable, and imaging studies showed tumour involving the bladder and prostate. Tumour markers and a CARIS genomic prevalence score also favoured a colorectal cancer primary.The patient refused surgery and underwent chemoradiation with a combination of EBRT and brachytherapy with concurrent capecitabine. Imaging studies obtained 6 months after reirradiation revealed an enlarged left-sided mesorectal lymph node concerning for disease recurrence. The lymph node was treated with Stereotactic Body Radiation Therapy and his post-treatment imaging revealed a response to treatment with no other evidence of disease.
Topics: Male; Humans; Urinary Bladder; Prostatic Neoplasms; Neoplasm Recurrence, Local; Brachytherapy; Urinary Bladder Neoplasms; Adenocarcinoma
PubMed: 37463778
DOI: 10.1136/bcr-2022-252747 -
Cancer Radiotherapie : Journal de La... Feb 2024In recent years, the development of both medical imaging and new systemic agents (targeted therapy and immunotherapy) have revolutionized the field of oncology, leading... (Review)
Review
In recent years, the development of both medical imaging and new systemic agents (targeted therapy and immunotherapy) have revolutionized the field of oncology, leading to a new entity: oligometastatic disease. Adding local treatment of oligometastases to systemic treatment could lead to prolonged survival with no significant impact on quality of life. Given the high prevalence of lung oligometastases and the new systemic agents coming with increased pulmonary toxicity, this article provides a comprehensive review of the current state-of-art for radiotherapy of lung oligometastases. After reviewing pretreatment workup, the authors define several radiotherapy regimen based on the localization and size of the oligometastases. A comment on the synergistic combination of medical treatment and radiotherapy is also made, projecting on future steps in this specific clinical setting.
Topics: Humans; Quality of Life; Radiosurgery; Lung; Lung Neoplasms; Diagnostic Imaging
PubMed: 38228422
DOI: 10.1016/j.canrad.2023.06.030 -
Radiotherapy and Oncology : Journal of... Sep 2023Stereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this...
PURPOSE
Stereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database.
METHODS
Patients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF.
RESULTS
A total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR.
CONCLUSION
SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.
Topics: Humans; Fractures, Spontaneous; Radiosurgery; Retrospective Studies; Lung Neoplasms; Incidence
PubMed: 37414253
DOI: 10.1016/j.radonc.2023.109792 -
Diagnostics (Basel, Switzerland) Dec 2023Interventional oncology (IO) is the field of Interventional Radiology that provides minimally invasive procedures under imaging guidance for the diagnosis and treatment... (Review)
Review
Interventional oncology (IO) is the field of Interventional Radiology that provides minimally invasive procedures under imaging guidance for the diagnosis and treatment of malignant tumors. Sophisticated devices can be utilized to increase standardization, accuracy, outcomes, and "repeatability" in performing percutaneous Interventional Oncology techniques. These technologies can reduce variability, reduce human error, and outperform human hand-to-eye coordination and spatial relations, thus potentially normalizing an otherwise broad diversity of IO techniques, impacting simulation, training, navigation, outcomes, and performance, as well as verification of desired minimum ablation margin or other measures of successful procedures. Stereotactic navigation and robotic systems may yield specific advantages, such as the potential to reduce procedure duration and ionizing radiation exposure during the procedure and, at the same time, increase accuracy. Enhanced accuracy, in turn, is linked to improved outcomes in many clinical scenarios. The present review focuses on the current role of percutaneous navigation systems and robotics in diagnostic and therapeutic Interventional Oncology procedures. The currently available alternatives are presented, including their potential impact on clinical practice as reflected in the peer-reviewed medical literature. A review of such data may inform wiser investment of time and resources toward the most impactful IR/IO applications of robotics and navigation to both standardize and address unmet clinical needs.
PubMed: 38201407
DOI: 10.3390/diagnostics14010098