A Meta-analysis of the Efficacy and Safety of Stereotactic Arrhythmia Radioablation (STAR) in Patients with Refractory Ventricular Tachycardia.

AIMS: Reports of stereotactic arrhythmia radioablation (STAR) in patients with refractory ventricular tachycardia after catheter ablation are limited to small series. Here, we carried out a systematic review and meta-analysis of studies to better determine the efficacy and toxicity of STAR for ventricular tachycardia. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines, eligible studies were identified on Medline, Embase, Cochrane Library and the proceedings of annual meetings to 10 February 2023. Efficacy was defined as a ventricular tachycardia burden reduction >70% at 6 months; safety was defined as <10% of any grade ≥3 toxicity. RESULTS: Seven observational studies with a total of 61 patients treated were included. At 6 months, the ventricular tachycardia burden reduction was 92% (95% confidence interval 85-100%) and use of fewer than two anti-arrhythmic drugs was seen in 85% (95% confidence interval 50-100). Six months after STAR, an 86% reduction (95% confidence interval 80-93) in the number of implantable cardioverter-defibrillator shocks was observed. The rates for improved, unchanged and decreased cardiac ejection fraction were 10%, 84% and 6%, respectively. Overall survival at 6 and 12 months was 89% (95% confidence interval 81-97) and 82% (95% confidence interval 65-98). The cardiac-specific survival at 6 months was 87%. Late grade 3 toxicity occurred in 2% (95% confidence interval 0-5%) with no grade 4-5 toxicity. CONCLUSION: STAR demonstrated both satisfactory efficacy and safety for the management of refractory ventricular tachycardia and was also associated with a significant decline in anti-arrhythmic drugs consumption. These findings support the continued development of STAR as a treatment option.

Stereotactic radiosurgery for brain metastases from small cell lung cancer without prior whole-brain radiotherapy: A meta-analysis.

OBJECTIVES: Assess upfront Stereotactic radiosurgery (SRS) effectiveness for small cell lung cancer (SCLC) brain metastases (BM). Where possible, a comparison with whole-brain radiotherapy (WBRT) was performed. METHODS: Following PRISMA and MOOSE guidelines, eligible studies were identified on Medline, Embase, Cochrane Library, and proceedings of annual meetings between inception and July 01, 2020. RESULTS: Nine observational studies with 1638 patients were included. The median overall survival (OS) was 8.3 months (95% CI 7.1-9.5 months, I2 = 0%). OS rate at 12 months was 39% (95% CI 31-44%, I2 = 0%). The relative risk between SRS and WBRT for the OS at 12 months was 1.33 (95% CI 1.13-1.51, P = 0.0001). The projected OS for 6, 12, 18- and 24-months comparing SRS with WBRT was 67% vs. 57%, 39% vs. 29%, 22% vs. 15% and 15% vs 9%, favoring SRS (P < 0.001). The LC rate at 12 months was 93% (95% CI 91-94%, I2 = 0%). The distant brain failure rate (DBFR) at 12 months was 41% (95% CI 33-48%, I2 = 52%, P = 0.08). The SRS or WBRT as salvage treatment after upfront SRS was 32% and 19%, respectively. The freedom from neurologic death at 12 months was 87% (95% CI 84-89%). CONCLUSION: Based on the pooling of a large sample of retrospective studies our meta-analysis suggests that for high selected SCLC patients with limited BM upfront SRS produces favorable lesion control and survival outcomes. These findings support the design of randomized clinical trial to confirm the role of SRS in this clinical scenario.

Focal Leptomeningeal Disease with Perivascular Invasion in EGFR-Mutant Non-Small-Cell Lung Cancer.

We report a previously undescribed pattern of brain metastases in patients with epidermal growth factor receptor-mutated non-small-cell lung cancer treated with tyrosine kinase inhibitors and radiation therapy. These highly distinct lesions appear to spread focally within the leptomeninges, with invasion along the perivascular spaces (FLIP). The survival of patients with FLIP was significantly better compared with patients with classic leptomeningeal disease (median survival, 21 versus 3 months; P = .003). It is unclear whether this pattern of growth is unique to epidermal growth factor receptor-mutated non-small-cell lung cancer.

Development and validation of a clinical prediction-score model for distant metastases in major salivary gland carcinoma.

BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.

Lives and Economic Loss in Brazil due to Lack of Radiotherapy Access in Cervical Cancer: A Cost-Effectiveness Analysis.

AIMS: Among all malignancies, the use of radiotherapy incurs the highest survival benefit within cervical cancers. Radiotherapy, however, remains underutilised for cervical cancers within the Brazilian public health system (BPHS). The objective of this study was to estimate the potential health and monetary benefits for universal access to radiotherapy and chemoradiotherapy (CRT) for untreated cervical cancer patients in the BPHS. MATERIALS AND METHODS: Using 2016 data on Brazilian cervical cancer incidence and availability of radiotherapy/CRT in the BPHS, the number of cancer deaths due to radiotherapy/CRT underutilisation was estimated. The incremental effectiveness was calculated by life-year gain. The indirect costs from mortality-related productivity loss (MRPL) were estimated based on life expectancy, wage and labour force participation rate. MRPL was compared with direct medical costs after being adjusted to 2016 US dollars. This study was conducted from the payer's perspective; both costs and effectiveness were discounted at a rate of 3%. The incremental cost-effectiveness ratio (ICER) was calculated to determine the cost-effectiveness of radiotherapy for cervical cancer in Brazil. One-way sensitivity analyses were carried out to assess the robustness of the model. RESULTS: The total number of life-years lost due to lack of universal access to radiotherapy and CRT per year were 27 199 and 31 627, respectively. The annual cost to match the radiotherapy gap was $10.5 million, with an additional cost of $3 million to close the CRT gap. The mean years of potential life lost per death was 20.5. The cost per life saved was $7942 for radiotherapy alone (ICER $388/life-year) and $8774 for CRT (ICER $429/life-year). MRPL due to shortage of radiotherapy and CRT were $59 million and $69 million, respectively. CONCLUSION: Providing universal access to radiotherapy/CRT for cervical cancer patients in the BPHS is highly cost-effective and should be prioritised as an impactful public health initiative.

Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System.

AIMS: Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. MATERIALS AND METHODS: Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. RESULTS: Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. CONCLUSION: Thousands of cancer patients requiring radiotherapy do not have access to this treatment in the Brazilian public health system. The shortage of radiotherapy has a significant detrimental effect on cancer survival; over 5000 deaths would probably be prevented in the most common cancer types if radiotherapy access was universal.