Purpose
We present the preliminary results of the STRA-MI-VT Study (NCT04066517), a spontaneous, phase Ib/II study, designed to prospectively test the safety and efficacy of stereotactic body ...radiotherapy (SBRT) in patientswith advanced cardiac disease and intractable ventricular tachycardia (VT).
Methods
Cardiac computed tomography (CT) integrated by electroanatomical mapping was used for substrate identification and merged with dedicated CT scans for treatment plan preparation. A single 25-Gy radioablation dose was delivered by a LINAC-based volumetric modulated arc therapy technique in a non-invasive matter. The primary safety endpoint was treatment-related adverse effects during acute and long-term follow-up (FU), obtained by regular in-hospital controls and implantable cardioverter defibrillator (ICD) remote monitoring. The primary efficacy endpoint was the reduction at 3 and 6 months of VT episodes and ICD shocks.
Results
Seven out of eight patients (men; age, 70 ± 7 years; ejection fraction, 27 ± 11%; 3 ischemic, 4 non-ischemic cardiomyopathies) underwent SBRT. At a median 8-month FU, no treatment-related serious adverse event occurred. Three patients died from non-SBRT-related causes. Four patients completed the 6-month FU: the number of VT decreased from 29 ± 33 to 11 ± 9 (
p
= .05) and 2 ± 2 (
p
= .08), at 3 and 6 months, respectively; shocks decreased from 11 to 0 and 2, respectively. At 6 months, all patients. showed a significant reduction of VT episodes and no electrical storm recurrence, with the complete regression of iterative VTs in 2/2 patients.
Conclusion
The STRA-MI-VT Study suggests that SBRT can be considered an alternative option for the treatment of VT in patients with structural heart disease and highlights the need for further clinical investigation addressing safety and efficacy.
For unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study ...reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort.
Two hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS).
One hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 65.5% (95%CI: 57.6-74.4) and 87.9% (95%CI: 82.26.6-93.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%).
Durvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice.
Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for ...both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics.
MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building.
Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients.
The study was prospectively registered at clinicaltrials.gov (NCT05974475).
the aim of this paper is to quantify multidisciplinary team meeting (MDT) impact on the decisional clinical pathway of thoracic cancer patients, assessing the modification rate of the initial ...out-patient evaluation.
the impact of MDT was classified as follows: confirmation: same conclusions as out-patient hypothesis; modification: change of out-patient hypothesis; implementation: definition of a clear clinical track/conclusion for patients that did not receive any clinical hypothesis; further exams required: the findings that emerged in the MDT meeting require further exams.
one thousand consecutive patients evaluated at MDT meetings were enrolled. Clinical settings of patients were: early stage lung cancer (17.4%); locally advanced lung cancer (27.4%); stage IV lung cancer (9.8%); mesothelioma (1%); metastases to the lung from other primary tumors (4%); histologically proven or suspected recurrence from previous lung cancer (15%); solitary pulmonary nodule (19.2%); mediastinal tumors (3.4%); other settings (2.8%).
MDT meetings impact patient management in oncologic thoracic surgery by modifying the out-patient clinical hypothesis in 10.6% of cases; the clinical settings with the highest decisional modification rates are "solitary pulmonary nodule" and "proven or suspected recurrence" with modification rates of 14.6% and 13.3%, respectively.
Abstract
Background
tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient’s life expectancy. The optimal treatment strategy ...for loco-regional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is not established yet.
This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery.
Methods
We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse.
Results
Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47–78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%.
Conclusions
In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery.
Purpose
Evaluation of target coverage and verification of safety margins, in motion management strategies implemented by Lung Optimized Treatment (LOT) module in CyberKnife system.
Methods
Three ...fiducial‐less motion management strategies provided by LOT can be selected according to tumor visibility in the X ray images acquired during treatment. In 2‐view modality the tumor is visible in both X ray images and full motion tracking is performed. In 1‐view modality the tumor is visible in a single X ray image, therefore, motion tracking is combined with an internal target volume (ITV)‐based margin expansion. In 0‐view modality the lesion is not visible, consequently the treatment relies entirely on an ITV‐based approach.
Data from 30 patients treated in 2‐view modality were selected providing information on the three‐dimensional tumor motion in correspondence to each X ray image. Treatments in 1‐view and 0‐view modalities were simulated by processing log files and planning volumes. Planning target volume (PTV) margins were defined according to the tracking modality: end‐exhale clinical target volume (CTV) + 3 mm in 2‐view and ITV + 5 mm in 0‐view. In the 1‐view scenario, the ITV encompasses only tumor motion along the non‐visible direction. Then, non‐uniform ITV to PTV margins were applied: 3 mm and 5 mm in the visible and non‐visible direction, respectively.
We defined the coverage of each voxel of the CTV as the percentage of X ray images where such voxel was included in the PTV. In 2‐view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the predicted target position, as recorded in log files. In 1‐view modality, coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the projected predictor data. In 0‐view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the non‐moving PTV.
Similar to dose‐volume histogram, CTV coverage‐volume histograms (defined as CVH) were derived for each patient and treatment modality. The geometric coverages of the 90% and 95% of CTV volume (C90, C95, respectively) were evaluated. Patient‐specific optimal margins (ensuring C95 ≥ 95%) were computed retrospectively.
Results
The median ± interquartile‐rage of C90 and C95 for upper lobe lesions was 99.1 ± 0.6% and 99.0 ± 3.1%, whereas they were 98.9 ± 4.2% and 97.8 ± 7.5% for lower and middle lobe tumors.
In 2‐view, 1‐view and 0‐view modality, adopted margins ensured C95 ≥ 95% in 70%, 85% and 63% of cases and C95 ≥ 90% in 90%, 88% and 83% of cases, respectively. In 2‐view, 1‐view and 0‐view a reduction in margins still ensured C95 ≥ 95% in 33%, 78% and 59% of cases, respectively.
Conclusions
CTV coverage analysis provided an a‐posteriori evaluation of the treatment geometric accuracy and allowed a quantitative verification of the adequacy of the PTV margins applied in CyberKnife LOT treatments offering guidance in the selection of CTV margins.
Purpose
To report criticisms and barriers to the “real-life” application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) ...in Italy.
Methods
Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice.
Results
A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of “surgical resectability” and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns.
Conclusion
The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application.
The purpose of this study is to collect available evidence on the feasibility and efficacy of stereotactic arrhythmia radio ablation (STAR), including both photon radiotherapy (XRT) and particle beam ...therapy (PBT), in the treatment of atrial fibrillation (AF), and to provide cardiologists and radiation oncologists with a practical overview on this topic.
Three hundred and thirty-five articles were identified up to November 2021 according to preferred reporting items for systematic reviews and meta-analyses criteria; preclinical and clinical studies were included without data restrictions or language limitations. Selected works were analyzed for comparing target selection, treatment plan details, and the accelerator employed, addressing workup modalities, acute and long-term side-effects, and efficacy, defined either by the presence of scar or by the absence of AF recurrence.
Twenty-one works published between 2010 and 2021 were included. Seventeen studies concerned XRT, three PBT, and one involved both. Nine studies (1
and 8
; doses ranging from 15 to 40 Gy) comprised a total of 59 animals, 12 (8
, 4
; doses ranging from 16 to 50 Gy) focused on humans, with 9 patients undergoing STAR: average follow-up duration was 5 and 6 months, respectively. Data analysis supported efficacy of the treatment in the preclinical setting, whereas in the context of clinical studies the main favorable finding consisted in the detection of electrical scar in 4/4 patients undergoing specific evaluation; the minimum dose for efficacy was 25 Gy in both humans and animals. No acute complication was recorded; severe side-effects related to the long-term were observed only for very high STAR doses in 2 animals. Significant variability was evidenced among studies in the definition of target volume and doses, and in the management of respiratory and cardiac target motion.
STAR is an innovative non-invasive procedure already applied for experimental treatment of ventricular arrhythmias. Particular attention must be paid to safety, rather than efficacy of STAR, given the benign nature of AF. Uncertainties persist, mainly regarding the definition of the treatment plan and the role of the target motion. In this setting, more information about the toxicity profile of this new approach is compulsory before applying STAR to AF in clinical practice.
Highlights • We determined localization and residual errors for 57 lung SBRT using CBCT. • Translational and rotational errors were detected using ITV/CBCT matching technique. • The automatic 6D ...correction with the robotic couch increased localization accuracy. • 5 mm safety margin to the ITV resulted adequate using the automatic 6D correction.
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