Patient vulnerability in stereotactic arrhythmia radioablation (STAR): a preliminary ethical appraisal from the STOPSTORM.eu consortium.

This preliminary ethical appraisal from the STOPSTORM.eu consortium is meant to raise critical points that clinicians administering stereotactic arrhythmia radioablation should consider to meet the highest standards in medical ethics and thus promote quality of life of patients recruited for radiotherapy treatments at a stage in which they experience a significant degree of vulnerability.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Intracranial chordoma: radiosurgery, hypofractionated stereotactic radiotherapy and treatment outcomes.

BACKGROUND: The aim of the study was to assess the results of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy (SRS/SRT) for skull base chordomas. MATERIALS AND METHODS: Twenty-three patients aged 12-75 were treated with SRS/SRT due to skull base chordoma. In 19 patients SRS/SRT was a part of the primary therapy, while in 4, a part of the treatment of recurrence. In 4 patients SRS/SRT was used as a boost after conventional radiotherapy and in 19 cases it was the only irradiation method applied. Patients were irradiated to total dose of 6-35 Gy and median total equivalent dose of 52 Gy. RESULTS: During median follow-up of 39 months, 4 patients died. One-, two- and five-year OS was 95%, 89% and 69%, respectively. In nine patients, progression of the disease was diagnosed during study period. One-, two- and five-year progression free survival (PFS) from the end of radiotherapy was 81%, 59% and 43%, respectively. Radiotherapy was well tolerated and only two patients in our group experienced moderate treatment-related toxicity. CONCLUSION: SRS/SRT alone or in combination with surgery is a safe and effective method of irradiation of patients with skull base chordomas. High EQD2 is necessary to achieve satisfactory treatment results.

Radiosurgery or hypofractionated stereotactic radiotherapy after craniospinal irradiation in children and adults with medulloblastoma and ependymoma.

PURPOSE: To assess the results and tolerance of radiosurgery/hypofractionated stereotactic radiotherapy performed after craniospinal irradiation for recurrent tumor. METHODS: Fourteen patients aged 3-46 years, diagnosed with medulloblastoma (10), anaplastic ependymoma (3), and primitive neuroectodermal tumor (1). All patients had craniospinal irradiation (CSI) with the total dose of 30.6-36 Gy and boost to 53.9-60 Gy either during primary or during second-line treatment. Twelve patients were irradiated with a single dose of 6-15 Gy (median 14.5 Gy). One received three fractions of 5 Gy and one six fractions of 5 Gy. In statistical analysis, the Kaplan-Meier method and log-rank test were used. The overall survival was calculated from the date of the end of stereotactic radiosurgery to the date of death or last contact. RESULTS: Recurrences were diagnosed after the median time of 16 months after the end of primary treatment. Eleven patients died during the follow-up. The follow-up for the 3 patients still alive was 6.7, 40.5, and 41.4 months, respectively. One- and 2-year overall survival (OS) was 70% and 39%. Patients who had ECOG performance status of 0 at the time of diagnosis of the disease trended to have better 2-year OS compared to those evaluated as ECOG 1 (p = 0.057). Treatment results were evaluable in 12 patients. Local control (stabilization or regression of the lesion) was achieved in 9 (75%). Overall disease progression was 67%. No patient developed radiation-induced necrosis. The treatment was well tolerated and no serious adverse effects were observed. Eleven patients were given steroids as a prevention of brain edema and four of them needed continuation of this treatment afterwards. In 7 patients, symptoms of brain edema were observed during the first weeks after reirradiation. CONCLUSIONS: Stereotactic radiosurgery or hypofractionated stereotactic radiotherapy is an effective treatment method of the local recurrence after CSI and can be performed safely in heavily pre-treated patients.

Cavernous sinus haemangioma with intrasellar extension mimicking non-functioning pituitary adenoma - A case report and review of literature.

Fifty-three-year-old male suffering from a presumptive non-functioning pituitary adenoma was qualified for stereotactic radiosurgery in our institution. Two attempts of surgical treatment were taken three months before radiotherapy. Excessive bleeding did not allow to remove the tumour or to take samples for histopathological examination. Diagnosis was put on the basis of radiological assessment and lack of hypersecretion of pituitary hormones. However, radiological reevaluation in our Institute revealed the presence of a well-bounded tumour invading the cavernous sinus with high contrast enhancement in FLAIR and T2-sequence. Moreover, a constriction of the normal pituitary gland with tumour mass was seen. The imaging features of the lesion finally led to diagnosis of cavernous sinus haemangioma with intrasellar expansion. The patient received radiosurgical treatment with the use of linear accelerator (LINAC). A dose of 7 Gy in one fraction was administered to achieve satisfactory local control, prevent potential further bleeding and reduce the risk of progressive neurological deficits. Stable size of the tumour and absence of any complications are confirmed in six years of follow-up.

Effect of Therapeutic Ionizing Radiation on Implantable Electronic Devices: Systematic Review and Practical Guidance.

Cardiac implantable electronic devices (CIEDs) have been in use for over 50 years and their therapeutic value is undisputable. With the rapidly aging population, it is estimated that the number of CIEDs will grow dramatically over the next 2 decades. Given these predictions, the topic of management of concomitant conditions associated with older age becomes more relevant than ever. In particular, the number of patients with an implanted CIED diagnosed with cancer is expected to rise by about 70%, from 14 million in 2012 to 22 million within the next 2 decades. Treatment of most of these tumors and tumor metastases requires radiation therapy. However, the necessary high doses of radiation can potentially interact with the function, longevity, and integrity of the CIEDs and/or cause harm to the patient. The impact of an absence of clear therapeutic guidelines for oncology patients with CIEDs who should undergo radiation therapy is vast; and due to the fear of possible complications related to device failure, many of these patients may not be treated adequately to their needs, which can strongly affect their prognosis. This article summarizes the available data on the management of patients with CIEDs undergoing radiotherapy. It systematically presents possible causes and consequences of direct and scattered radiation on CIEDs, highlights possible complications that may occur during this kind of treatment, and provides practical guidance for this challenging real life clinical setting.

Tracheal cancer - treatment results, prognostic factors and incidence of other neoplasms.

BACKGROUND: Tracheal cancers (TC) are rare and treatment results that are reported are typically not satisfactory. The purpose of this research was assessment of the results of treatment of TC patients, identification of potential additional surgery candidates, evaluation of prognostic factors, and assessment of the occurrence of other malignancies. PATIENTS AND METHODS: The Regional Cancer Database and the Hospital Database were searched for patients with tracheal neoplasms. Fifty-eight of 418 patients identified initially, met the inclusion criteria (primary TC with confirmed histology and complete treatment records). Standard statistical tests were used. RESULTS: Squamous cell carcinoma (SCC; 63.8%) and adenoid cystic carcinoma (ACC; 15.5%) were the most commonly diagnosed histological types of TC. Radiotherapy was delivered in 48 cases, surgery or endoscopic resection in 20, and chemotherapy in 14. TC was diagnosed as a second cancer in 10 patients, in 1 patient it occurred prior to the lung cancer, and in 1 was diagnosed simultaneously. During the median follow-up of 12.7 months, 85.5% of the patients died because of the disease. Local recurrence occurred in 17% cases. In univariate analysis, patients with ACC had statistically better five-year overall survival (77.8%) than those diagnosed with SCC (8.4%, p = 0.0001). Radiotherapy, performance status and haemoptysis were factors significantly influencing overall survival (OS) in the multivariate analysis. Among patients who were not treated surgically, 15-26% were found to constitute additional surgery candidates, depending on the selection criteria. CONCLUSIONS: The diagnostic workup should be focused on the identification of TC patients suitable for invasive treatment and radiotherapy. Respiratory system cancer survivors can be considered a risk group for tracheal cancer. Radiotherapy constitutes an important part of the treatment of patients with TC.

Evaluation of efficacy and safety of robotic stereotactic body radiosurgery and hypofractionated stereotactic radiotherapy for vertebral metastases.

AIM OF THE STUDY: The purpose of this study was to evaluate the efficacy and safety of applying CyberKnife (CK) radiosurgery in patients with spinal metastases. MATERIAL AND METHODS: Twenty-eight patients with vertebral metastases treated using the CK system were included in the study. Eleven patients suffered from pain, and in 1 case neurological symptoms were observed. The remaining patients were free from clinical symptoms of metastatic disease. The doses applied ranged between 8 and 40 Gy delivered in 4 fractions of 8-15 Gy. RESULTS: In the first follow-up evaluation (mean 4.5 months after the treatment), pain was stable in 5 of 8 evaluable cases and in 3 regression occurred. The last follow-up examination (mean 11 months after stereotactic radiosurgery) revealed stable ailments in 3 of 6 evaluable cases, improvement in 3 and new complaints in another 4 patients. In 17 patients imaging studies were conducted after a mean time of 11 months after CK treatment. Stabilization was confirmed in 11, regression in 4 and progression in 2 cases. Median overall survival was 20.6 months. Median progression-free survival was 12.6 months. No side effects attributable to the treatment were observed, but during follow-up transient or permanent deterioration in neurological status as a consequence of disease progression was diagnosed in 4 patients. Delivery time of a single fraction ranged between 0.5 and 1.5 hours. CONCLUSIONS: Robotic stereotactic radiosurgery as part of multimodality therapy for metastatic spinal tumours is safe and effective. Because of long irradiation times, this kind of treatment is not suitable for patients in poor general condition.

Tolerability and toxicity of prophylactic cranial irradiation in patients with non-small cell lung cancer - Results of a phase II study (with estimation of hematological toxicity, pituitary function and magnetic resonance spectra changes).

AIM: To evaluate the tolerability and toxicity of PCI in patients with NSCLC. BACKGROUND: Prophylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment. MATERIALS AND METHODS: From 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30 Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with (1)H nuclear magnetic resonance spectra, and estimation of pituitary function. RESULTS: During follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease (p = 0.062). Visual-motor function deteriorated after treatment (p < 0.059). Performance IQ decreased (p < 0.025) and the difference between performance IQ and verbal IQ increased (p < 0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI. CONCLUSION: PCI in the current series was well tolerated and associated with a relatively low toxicity.

Stereotactic linac radiosurgery and hypofractionated stereotactic radiotherapy for pediatric arteriovenous malformations of the brain: experiences of a single institution.

PURPOSE: The aim of our study was to evaluate treatment results and toxicity of stereotactic irradiation for arteriovenous malformations (AVMs) in children. METHODS: A group of ten consecutive children (four boys and six girls) irradiated between 2002 and 2010 at our institution was included into the study. The mean age at the time of treatment was 15.4 and ranged between 8 and 18 years. There were two Spetzler-Martin grade IV, four grade III, and four grade II lesions. Mean AVM volume was 13.2 cm(3) and varied from 0.6 to 36.8 cm(3). In five patients, the planned dose of 16-20 Gy was delivered in single fraction, in five the total dose of 16-24 Gy was delivered in two to three fractions. One patient was reirradiated with a dose of 15 Gy, 7 years after the initial treatment. RESULTS: The median follow-up was 38.5 months. The treatment resulted in total obliteration in eight patients and partial in one. The median time to obliteration was 22 months; actuarial total obliteration rates were 20, 54, 54, and 83 % after 1, 2, 3, and 4 years of follow-up, respectively. No patient bled after the treatment. In one patient, new epileptic seizures developed after the treatment; in magnetic resonance imaging, focal necrosis was revealed. In five patients, asymptomatic imaging abnormalities were seen during follow-up. CONCLUSIONS: Stereotactic radiotherapy appears to be an effective method of treatment for pediatric AVMs, the patients however require meticulous follow-up because of relative high incidence of radiation-induced imaging abnormalities.

Hypofractionated stereotactic radiotherapy for large or involving critical organs cerebral arteriovenous malformations.

BACKGROUND: The treatment of large arteriovenous malformations (AVMs) or AVMs involving eloquent regions of the brain remains a challenge. For inoperable lesions, observation, volume-staged radiosurgery or hypofractionated stereotactic radiotherapy (HFSRT) are proposed. The aim of our study was to assess the safety and efficiency of HFSRT for large AVMs located in eloquent areas of the brain. MATERIALS AND METHODS: An analysis of records of 49 patients irradiated for cerebral AVMs with a mean dose of 19.9 Gy (12-28 Gy) delivered in 2-4 fractions with planned gap (at least one week) between fractions. Actuarial obliteration rates and annual bleeding hazard were calculated using Kaplan-Meier survival analysis and life tables. RESULTS: Annual bleeding hazard rates were 4.5% and 1.6% after one and two years of the follow-up, respectively. Actuarial total obliteration rates were 7%, 11%, and 21% and total response rate (total and partial obliterations) 22%, 41%, and 55% after one, two and three years of the follow-up, respectively. There was a trend towards larger total obliteration rate in patients irradiated with fraction dose ≥ 8 Gy and total dose > 21 Gy for lesions of volume ≤ 8.18 cm(3) which was not observed in case of partial obliterations. CONCLUSIONS: HFSRT results with relatively low obliteration rate but is not associated with a significant risk of permanent neurological deficits if both total and fraction doses are adjusted to size and location of the lesion. Predictive factors for total and partial obliterations can be different; this observation, however, is not firmly supported and requires further studies.

The Price of Success-The Long-Term Outcomes of Children with Craniopharyngioma-Two Institutions' Experience.

An analysis of patients below 21 years old treated due to craniopharyngioma in the years 1979-2022 was performed with the aim of evaluating the long-term outcome and treatment side-effects. The standard statistical tests were used, and 56 patients with a median age of 11 years were evaluated. Surgery was the primary treatment in 55 patients; however, in only 29 it was the only neurosurgical intervention. Eighteen children were treated with radiotherapy (RTH) in primary treatment. The most common neurosurgical side effects observed were visual and endocrine deficits and obesity, which were diagnosed in 27 (49%), 50 (91%), and 25 (52%) patients, respectively. Complications after RTH were diagnosed in 14 cases (32%). During the median follow-up of 8.4 years (range: 0.4-39.8 years), six patients died and the 5- and 10-year overall survival was 97% and 93%, respectively. Five-year progression-free survival for gross total resection, resection with adjuvant RTH, and non-radical resection alone was 83%, 68%, and 23%, respectively (p = 0.0006). Surgery combined with RTH provides comparable results to gross tumor resection in terms of oncologic outcome in craniopharyngioma patients. Adjuvant irradiation applied in primary or salvage treatment improves disease control. The rate of complications is high irrespective of improved surgical and radiotherapeutic management.

Heat shock protein A2 is a novel extracellular vesicle-associated protein.

70-kDa Heat Shock Proteins (HSPA/HSP70) are chaperones playing a central role in the proteostasis control mechanisms. Their basal expression can be highly elevated as an adaptive response to environmental and pathophysiological stress conditions. HSPA2, one of poorly characterised chaperones of the HSPA/HSP70 family, has recently emerged as epithelial cells differentiation-related factor. It is also commonly expressed in cancer cells, where its functional significance remains unclear. Previously, we have found that proteotoxic stress provokes a decrease in HSPA2 levels in cancer cells. In the present study we found that proteasome inhibition-related loss of HSPA2 from cancer cells neither is related to a block in the gene transcription nor does it relate to increased autophagy-mediated disposals of the protein. Proteotoxic stress stimulated extracellular release of HSPA2 in extracellular vesicles (EVs). Interestingly, EVs containing HSPA2 are also released by non-stressed cancer and normal cells. In human urinary EVs levels of HSPA2 were correlated with the levels of TSG101, one of the main EVs markers. We conclude that HSPA2 may constitute basic components of EVs. Nevertheless, its specific role in EVs and cell-to-cell communication requires further investigation.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. OBJECTIVE: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. METHODS: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. DISCUSSION: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure. TRIAL REGISTRATION: NCT05594368.

Stereotactic management of arrhythmia - radiosurgery in treatment of ventricular tachycardia (SMART-VT). Results of a prospective safety trial.

BACKGROUND AND PURPOSE: Despite its increasing popularity, there are limited prospective data on stereotactic arrhythmia radioablation (STAR). In this trial, we assessed the safety and efficacy of STAR in patients with ventricular tachycardia (VT), focusing on early treatment-related grade ≥ 3 adverse events (AE). MATERIALS AND METHODS: This prospective trial was designed for adults with VT recurrence following catheter ablation (CA) despite adequate pharmacotherapy, or contraindications to CA. A single dose of 25 Gy was delivered to the arrhythmia substrate defined on electro-anatomic mapping and cardiac-gated CT. The primary endpoint was safety, defined as two or fewer treatment-related grade ≥ 3 AEs during the first three months in 11 patients. Additional endpoints included treatment efficacy, clinical and biological markers of cardiac injury, and quality of life. RESULTS: Eleven patients with a median age of 67 years, structural heart disease, and a clinically significant recurrence of VT despite adequate pharmacotherapy and 1-4 previous CAs were enrolled between 2020/09 and 2022/10. Following the treatment, one patient developed a possibly treatment-related grade ≥ 3 AE, a grade 4 heart failure exacerbation at 87 days, which resolved after conservative treatment. There was a total 84.3% reduction in VT burden in 10 evaluable patients; however, VT recurrence was eventually observed in eight, and three patients required additional CAs. Three deaths due to unrelated causes were recorded. CONCLUSIONS: STAR appears to be safe and efficient. It is a promising treatment for selected patients; however, long-term outcomes remain to be evaluated, and controlled trials comparing STAR with standards of care are missing.

Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT.

Splenomegaly is a hallmark of myelofibrosis, a debilitating haematological malignancy for which the only curative option is allogeneic haematopoietic cell transplantation (HCT). Considerable splenic enlargement might be associated with a higher risk of delayed engraftment and graft failure, increased non-relapse mortality, and worse overall survival after HCT as compared with patients without significantly enlarged splenomegaly. Currently, there are no standardised guidelines to assist transplantation physicians in deciding optimal management of splenomegaly before HCT. Therefore, the aim of this Position Paper is to offer a shared position statement on this issue. An international group of haematologists, transplantation physicians, gastroenterologists, surgeons, radiotherapists, and radiologists with experience in the treatment of myelofibrosis contributed to this Position Paper. The key issues addressed by this group included the assessment, prevalence, and clinical significance of splenomegaly, and the need for a therapeutic intervention before HCT for the control of splenomegaly. Specific scenarios, including splanchnic vein thrombosis and COVID-19, are also discussed. All patients with myelofibrosis must have their spleen size assessed before allogeneic HCT. Myelofibrosis patients with splenomegaly measuring 5 cm and larger, particularly when exceeding 15 cm below the left costal margin, or with splenomegaly-related symptoms, could benefit from treatment with the aim of reducing the spleen size before HCT. In the absence of, or loss of, response, patients with increasing spleen size should be evaluated for second-line options, depending on availability, patient fitness, and centre experience. Splanchnic vein thrombosis is not an absolute contraindication for HCT, but a multidisciplinary approach is warranted. Finally, prevention and treatment of COVID-19 should adhere to standard recommendations for immunocompromised patients.

Radiosurgery in Treatment of Ventricular Tachycardia - Initial Experience Within the Polish SMART-VT Trial.

Background: Stereotactic Arrhythmia Radioablation (STAR) is an emerging treatment modality for patients with sustained ventricular tachycardia (VT) and refractory to treatment with drugs and radiofrequency catheter ablation (RFA). It is believed that up to 12-17% of patients experience recurrence of VT within 1 year of follow-up; thus, novel therapeutic options are needed. The aim of this article is to present initial experience within a novel treatment modality for VT. Case Summary: Two patients with a medical history of coronary artery disease and heart failure with reduced left ventricle (LV) ejection fraction, after implantation of cardioverter-defibrillator (ICD) and previous unsuccessful RFAs owing to sustained VT were admitted to the cardiology department due to recurrence of sustained VT episodes. With electroanatomical mapping (EAM), the VT substrate in LV has been confirmed and specified. In order to determine the target volume for radioablation, contrast-enhanced computed tomography was performed and the arrhythmia substrate was contoured using EAM data. Using the Volumetric Modulated Arc Therapy technique and three 6 MeV flattening filter-free photon beam fields, a single dose of 25 Gy was delivered to the target volume structure located in the apex and anterior apical segments of LV in the first patient and in the apex, anterolateral and inferior apical segments of the second patient. In both cases, volumes of the target structures were comparable. Interrogation of the implanted ICD at follow-up visits throughout 6 months after the treatment revealed no VT episodes in the first patient and sudden periprocedural increase in VT burden with a subsequent gradual decrease of ventricular arrhythmia to only two non-sustained episodes at the end of the follow-up period in case of the second patient. A significant reduction in premature ventricular contractions burden was observed compared to the pre-treatment period. No noticeable deterioration in LV function was noted, nor any adverse effects of radiosurgery associated with the implanted device. Conclusion: The early response to STAR can be unpredictable and probably does not reflect the final outcome of irradiation. Close monitoring of patients, especially in the early period after irradiation is crucial to properly handle potentially harmful early reactions to STAR.

Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation).

Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.

A new prognostic score for predicting survival in patients treated with robotic stereotactic radiotherapy for brain metastases.

The study aimed to analyze potential prognostic factors in patients treated with robotic radiosurgery for brain metastases irrespective of primary tumor location and create a simple prognostic score that can be used without a full diagnostic workup. A retrospective analysis of 142 patients with 1-9 brain metastases treated with stereotactic radiosurgery (1-4 fractions) was performed. Volumes of all lesions were calculated using linear dimensions of the tumors (CC, LR, AP) and 4/3*π*(CC/2)*(LR/2)*(AP/2) formula. Kaplan-Meier method and log-rank test were used to analyze survival. Variables significantly associated with overall survival in univariate analysis were included in Cox multivariate analysis. The validity of the model was tested with the bootstrap method. Variables from the final model were used to construct a new prognostic index by assigning points according to the impact of a specific variable on overall survival. In the multivariate analysis, four factors: Karnofsky Performance Status (p = 0.000068), number of brain metastases (p = 0.019), volume of the largest lesion (p = 0.0037), and presence of extracerebral metastases (p = 0.0017), were independent predictors of survival. Total scores ranged from 0 to 12 points, and patients were divided into four groups based on median survival of each subgroup: 0-1 points-18.8 months, 2-3 points-16.9 months, 4-5 points-5.6 months, and ≥ 6 points-4.9 months (p < 0.001). The new prognostic index is simple to calculate. It has a strong prognostic value in a heterogeneous population of patients with a various number of brain metastases, but its value requires confirmation in another cohort.

Clinical Evidence behind Stereotactic Radiotherapy for the Treatment of Ventricular Tachycardia (STAR)-A Comprehensive Review.

The electrophysiology-guided noninvasive cardiac radioablation, also known as STAR (stereotactic arrhythmia radioablation) is an emerging treatment method for persistent ventricular tachycardia. Since its first application in 2012 in Stanford Cancer Institute, and a year later in University Hospital Ostrava, Czech Republic, the authors from all around the world have published case reports and case series, and several prospective trials were established. In this article, we would like to discuss the available clinical evidence, analyze the potentially clinically relevant differences in methodology, and address some of the unique challenges that come with this treatment method.