Ablative Radiotherapy Research Articles

PO-715-08 NOVEL WORKFLOW FOR ELECTROANATOMIC MAP INTEGRATION FOR CARDIAC RADIATION ABLATION OF VENTRICULAR TACHYCARDIA

Cardiac Radiation Ablation (CRA) is an emerging therapy for reducing recurrent Ventricular Tachycardia (VT) that is refractory to pharmacologic therapy and standard catheter ablation. Electroanatomic Maps (EAM) delineating important details of the VT substrate are created during catheter ablation, but the absence of established workflows to facilitate integration of EAM data into standard radiation treatment planning software (TPS) limits their use.

PO-687-03 TRANSIENT DYSFUNCTION OF CARDIAC RESYNCHRONIZATION THERAPY DEFIBRILLATOR SYSTEM FOLLOWING CARDIAC RADIATION ABLATION

Cardiac Radiation Ablation (CRA) for reducing recurrent Ventricular Tachycardia (VT) that is refractory to conventional treatment is an emerging therapy. There is little data regarding effects of CRA on cardiac implanted electronic devices (CIED). Established guidelines related to CIEDs in radiation therapy may not be appropriate for CRA. To report incidence of transient CIED dysfunction during and after CRA despite adherence to established radiation therapy guidelines. N/A A 72 year old man with history of ischemic cardiomyopathy, CRT-D, and recurrent, symptomatic ventricular tachycardia refractory to multiple catheter ablation procedures presented for CRA. Multimodality evaluation for determination of CRA target volume included electranamatomic mapping from catheter ablation procedures, non-invasive programmed stimulation with noninvasive ECGi mapping (CardioInsight, Medtronic, Inc.), cardiac MRI, and 4DCT. A radiation treatment plan delivering 2500 cGy to a basal, inferior left ventricular target. The minimum field edge to CIED was ∼5 cm. The patient underwent CRA with arms raised over his head, a magnet and dosimeter which measured 8.5 cGy during CRA (200 cGy recommended limit) over his CRT-D, and abdominal compression. During the final minutes of CRA, the heart rate elevated from 60bpm to 70bpm, and the patient developed palpitations that were determined to be new phrenic nerve stimulation with LV lead position stability confirmed on CXR. Pacing rate change was determined on interrogation of Biotronik CRT-D be due to device reset, and new phrenic nerve capture, and elevated myocardial pacing threshold were noted at the two basal electrodes on the quadripolar LV lead. Both phrenic capture and threshold elevation were resolved on post-CRA day #1. To our knowledge, this is the first known occurrence of CIED reset and acute changes in pacing parameters related to CRA. The CIED soft reset was most likely due to a neutron interaction from CRA. The etiology of acute changes in pacing parameters remains unclear. Close monitoring of CIEDs during and after CRA is advisable.

Multidisciplinary Treatment of Non-Spine Bone Metastases: Results of a Modified Delphi Consensus Process

PurposeLocal treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and MaterialsA multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating “agree” or “strongly agree” with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. ResultsSeventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). ConclusionsConsensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases

PurposeRandomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and MaterialsThe RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. ResultsNinety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. ConclusionsTo our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study \u2013 a phase I/II clinical trial protocol

BackgroundBreast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients.MethodsThis is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3–4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate.DiscussionThe study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale.Trial registrationThe study was prospectively registered at clinicaltrials.gov (NCT04679454).

Stereotactic ablative radiation therapy for renal cell carcinoma with inferior vena cava tumor thrombus.

Inferior vena cava tumor thrombus (IVC-TT) is a rare yet deadly sequel of renal cell carcinoma (RCC) with limited treatment options. The standard treatment is extirpative surgery, which has high rates of morbidity and mortality. As a result, many patients are unfit or unwilling to undergo surgery and face poor prognosis. This stresses the need for alternative options for local disease control. Our study aims to assess the feasibility and oncological outcomes of stereotactic ablative radiation (SAbR) for IVC-TT. A retrospective study reviewing six leading international institutions' experience in treating RCC with IVC-TT with SAbR. Primary end point was overall survival using Kaplan-Meier. Fifteen patients were included in the cohort. Over 50% of patients had high level IVC-TT (level III or IV), 66.7% had metastatic disease. Most eschewed surgery due to high surgical risk (7/15) or recurrent thrombus (3/15). All patients received SAbR to the IVC-TT with a median biologically equivalent dose (BED10) of 72 Gy (range: 37.5-100.8) delivered in a median of 5 fractions (range 1-5). Median overall survival was 34 months. Radiographic response was observed in 58% of patients. Symptom palliation was recorded in all patients receiving SAbR for this indication. Only grade 1 to 2 adverse events were noted. SAbR for IVC-TT appears feasible and safe. In patients who are not candidates for surgery, SAbR may palliate symptoms and improve outcomes. SAbR may be considered as part of a multimodal treatment approach for patients with RCC IVC-TT.

A simulated comparison of lung tumor target verification using stereoscopic tomosynthesis or radiography.

Mobile lung tumors are increasingly being treated with ablative radiotherapy, for which precise motion management is essential. In-room stereoscopic radiography systems are able to guide ablative radiotherapy for stationary cranial lesions but not optimally for lung tumors unless fiducial markers are inserted. We propose augmenting stereoscopic radiographic systems with multiple small x-ray sources to provide the capability of imaging with stereoscopic, single frame tomosynthesis. In single frame tomosynthesis, nine x-ray sources are placed in a 3×3 configuration and energized simultaneously. The beams from these sources are collimated so that they converge on the tumor and then diverge to illuminate nine non-overlapping sectors on the detector. These nine sector images are averaged together and filtered to create the tomosynthesis effect. Single frame tomosynthesis is intended to be an alternative imaging mode for existing stereoscopic systems with a field of view that is three times smaller and a temporal resolution equal to the frame rate of the detector. We simulated stereoscopic tomosynthesis and radiography using Monte Carlo techniques on 60 patients with early-stage lung cancer from the NSCLC-Radiomics dataset. Two board-certified radiation oncologists reviewed these simulated images and rated them on a 4-point scale (1: tumor not visible; 2: tumor visible but inadequate for motion management; 3: tumor visible and adequate for motion management; 4: tumor visibility excellent). Each tumor was independently presented four times (two viewing angles from radiography and two viewing angles from tomosynthesis) in a blinded fashion over two reading sessions. The fraction of tumors that were rated as adequate or excellent for motion management (scores 3 or 4) from at least one viewing angle was 53% using radiography and 90% using tomosynthesis. From both viewing angles, the corresponding fractions were 7% for radiography and 48% for tomosynthesis. Readers agreed exactly on 62% of images and within 1 point on 98% of images. The acquisition technique was estimated to be 75 mAs at 120 kVp per treatment fraction assuming one verification image per breath, approximately one order of magnitude less than a standard dose cone beam CT. Stereoscopic tomosynthesis may provide a noninvasive, low dose, intrafraction motion verification technique for lung tumors treated by ablative radiotherapy. The system architecture is compatible with real-time video capture at 30 frames per second. Simulations suggest that most, but not all, lung tumors can be adequately visualized from at least one viewing angle.

Contrast-enhanced ultrasonography for blood flow detection in hepatocellular carcinoma during lenvatinib therapy

Blood flow reduction after initiation of lenvatinib therapy may not always indicate tumor necrosis. This study aimed to compare the blood flow detectability of contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma (HCC) during lenvatinib therapy. A total of 12 cases underwent CEUS and contrast-enhanced CT/MRI within 2weeks during lenvatinib therapy. Vascularity on CEUS and CT/MRI was compared. At the time of CEUS examination, the median period from the start of lenvatinib was 227 ± 210 (31-570) days. CEUS showed hyperenhancement in eight cases (66.7%), hypoenhancement in two cases (16.7%), and no enhancement in one case (8.3%), while CT/MRI showed hyperenhancement in one case (8.3%), ring enhancement in three cases (25.0%), and hypoenhancement in eight cases (66.7%) (p = 0.007). Transarterial chemoembolization (n = 3), radiofrequency ablation (n = 2), and stereotactic body radiation therapy (n = 2) were performed after blood flow detection by CEUS. The viability of the HCC should be confirmed using CEUS when contrast-enhanced CT/MRI reveals lesion hypoenhancement during lenvatinib therapy.

225Ac-rHDL Nanoparticles: A Potential Agent for Targeted Alpha-Particle Therapy of Tumors Overexpressing SR-BI Proteins.

Actinium-225 and other alpha-particle-emitting radionuclides have shown high potential for cancer treatment. Reconstituted high-density lipoproteins (rHDL) specifically recognize the scavenger receptor B type I (SR-BI) overexpressed in several types of cancer cells. Furthermore, after rHDL-SR-BI recognition, the rHDL content is injected into the cell cytoplasm. This research aimed to prepare a targeted 225Ac-delivering nanosystem by encapsulating the radionuclide into rHDL nanoparticles. The synthesis of rHDL was performed in two steps using the microfluidic synthesis method for the subsequent encapsulation of 225Ac, previously complexed to a lipophilic molecule (225Ac-DOTA-benzene-p-SCN, CLog P = 3.42). The nanosystem (13 nm particle size) showed a radiochemical purity higher than 99% and stability in human serum. In vitro studies in HEP-G2 and PC-3 cancer cells (SR-BI positive) demonstrated that 225Ac was successfully internalized into the cytoplasm of cells, delivering high radiation doses to cell nuclei (107 Gy to PC-3 and 161 Gy to HEP-G2 nuclei at 24 h), resulting in a significant decrease in cell viability down to 3.22 ± 0.72% for the PC-3 and to 1.79 ± 0.23% for HEP-G2 at 192 h after 225Ac-rHDL treatment. After intratumoral 225Ac-rHDL administration in mice bearing HEP-G2 tumors, the biokinetic profile showed significant retention of radioactivity in the tumor masses (90.16 ± 2.52% of the injected activity), which generated ablative radiation doses (649 Gy/MBq). The results demonstrated adequate properties of rHDL as a stable carrier for selective deposition of 225Ac within cancer cells overexpressing SR-BI. The results obtained in this research justify further preclinical studies, designed to evaluate the therapeutic efficacy of the 225Ac-rHDL system for targeted alpha-particle therapy of tumors that overexpress the SR-BI receptor.

Ablative Radiotherapy (ART) for Locally Advanced Pancreatic Cancer (LAPC): Toward a New Paradigm?

Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of intensive multi-agent chemotherapy regimens and aggressive surgical approaches, the survival of LAPC patients has significantly improved. In this complex and rapidly evolving scenario, the role of radiotherapy is still debated. The use of standard-dose conventional fractionated radiotherapy in LAPC has led to unsatisfactory oncological outcomes. However, technological advances in radiation therapy over recent years have definitively changed this paradigm. The use of ablative doses of radiotherapy, in association with image-guidance, respiratory organ-motion management, and adaptive protocols, has led to unprecedented results in terms of local control and survival. In this overview, principles, clinical applications, and current pitfalls of ablative radiotherapy (ART) as an emerging treatment option for LAPC are discussed.

Photodynamic therapy for stage I and II non-small cell lung cancer: A SEER-Medicare analysis 2000-2016.

We analyzed mortality (all-cause and lung cancer-specific) and time to follow-up treatment in stage I and II non-small cell lung cancer (NSCLC) patients treated with photodynamic therapy (PDT) compared with ablation therapy and radiation therapy.From Surveillance, Epidemiology, and End Results-Medicare linked data, patients diagnosed with stage I and II NSCLC between 2000 and 2015 were identified. Outcomes were mortality (overall and lung cancer-specific) and time to follow-up treatment. We analyzed mortality using Cox proportional hazard models. We used generalized linear model to assess time to follow-up treatment (PDT and ablation groups). Models were adjusted for inverse probability weighted propensity score.Of 495,441 NSCLC patients, 56 with stage I and II disease received PDT (mono or multi-modal), 477 received ablation (mono or multi-modal), and 14,178 received radiation therapy alone. None from PDT group had metastatic disease (M0) and 70% had no nodal involvement (N0). Compared with radiation therapy alone, PDT therapy was associated with lower hazard of overall (hazard ratio = 0.56, 95% CI = 0.39-0.80), and lung cancer-specific mortality (hazard ratio = 0.64, 95% CI = 0.43-0.97). Unadjusted mean time to follow-up treatment was 70days (standard deviation = 146) for PDT group and 67 days (standard deviation = 174) for ablation group. Compared with ablation, PDT was associated with an average increase of 125days to follow-up treatment (P = .11).Among stage I and II NSCLC patients, PDT was associated with improved survival, compared with radiation alone; and longer time to follow-up treatment compared with ablation. Currently, PDT is offered in various combinations with surgery and radiation. Larger studies can investigate the efficacy and effectiveness of these combinations.

Computed tomography-based radiomic to predict resectability in locally advanced pancreatic cancer treated with chemotherapy and radiotherapy.

BACKGROUNDSurgical resection after neoadjuvant treatment is the main driver for improved survival in locally advanced pancreatic cancer (LAPC). However, the diagnostic performance of computed tomography (CT) imaging to evaluate the residual tumour burden at restaging after neoadjuvant therapy is low due to the difficulty in distinguishing neoplastic tissue from fibrous scar or inflammation. In this context, radiomics has gained popularity over conventional imaging as a complementary clinical tool capable of providing additional, unprecedented information regarding the intratumor heterogeneity and the residual neoplastic tissue, potentially serving in the therapeutic decision-making process.AIMTo assess the capability of radiomic features to predict surgical resection in LAPC treated with neoadjuvant chemotherapy and radiotherapy.METHODSPatients with LAPC treated with intensive chemotherapy followed by ablative radiation therapy were retrospectively reviewed. One thousand six hundred and fifty-five radiomic features were extracted from planning CT inside the gross tumour volume. Both extracted features and clinical data contribute to create and validate the predictive model of resectability status. Patients were repeatedly divided into training and validation sets. The discriminating performance of each model, obtained applying a LASSO regression analysis, was assessed with the area under the receiver operating characteristic curve (AUC). The validated model was applied to the entire dataset to obtain the most significant features.RESULTSSeventy-one patients were included in the analysis. Median age was 65 years and 57.8% of patients were male. All patients underwent induction chemotherapy followed by ablative radiotherapy, and 19 (26.8%) ultimately received surgical resection. After the first step of variable selections, a predictive model of resectability was developed with a median AUC for training and validation sets of 0.862 (95%CI: 0.792-0.921) and 0.853 (95%CI: 0.706-0.960), respectively. The validated model was applied to the entire dataset and 4 features were selected to build the model with predictive performance as measured using AUC of 0.944 (95%CI: 0.892-0.996).CONCLUSIONThe present radiomic model could help predict resectability in LAPC after neoadjuvant chemotherapy and radiotherapy, potentially integrating clinical and morphological parameters in predicting surgical resection.

DEHART: Dose-Escalated Hypofractionated Adaptive Radiation Therapy with Atezolizumab for Head and Neck Cancers

<h3>Purpose/Objective(s)</h3> To determine the maximum-tolerated dose (MTD) of Dose-Escalated Hypofractionated Adaptive Radiation Therapy (DEHART) delivered with concurrent atezolizumab (Genentech) in patients with locally advanced or <i>de novo</i> metastatic head and neck squamous cell carcinomas (HNSCCs). (ClinicalTrials.Gov Identifier NCT04477759) We hypothesize that using DEHART we will be able to safely deliver ablative radiation doses for HNSCC in 15 fractions. <h3>Materials/Methods</h3> This is an NIH-funded (R21 CA256144-01) Phase I dose-escalation trial to determine the MTD of weekly adapted MR-guided radiation therapy delivered using the DEHART regimen with concurrent atezolizumab for patients with locoregionally advanced or <i>de novo</i> metastatic HNSCCs. Eligible patients are 18 years or older including all patients presenting with <i>de novo</i> metastatic HNSCC or patients presenting with localized AJCC 8^th edition T3-T4 N0-N3, T0-T4 N1-N3 HNSCC who meet at least one of the following criteria: 1) they are not candidates for concurrent bolus cisplatin; 2) they refuse concurrent cisplatin-based chemoradiation; 3) they have unresected or unresectable oral cavity cancer; or 4) they have recurrent disease after definitive surgical resection. DEHART is a novel adaptive MR-guided radiation regimen in which the gross tumor volume (GTV) plus a 3 mm PTV margin receives the experimental dose (50 Gy, 55 Gy or 60 Gy) in 15 fractions, a 1 cm anatomically-confined margin on the GTV plus a 3 mm PTV margin receives 45 Gy in 15 fractions, and elective lymph node basins plus a 3 mm PTV margin receives 40 Gy in 15 fractions. On fractions 6 and 11 of radiation, the GTV volume is adapted based on MR-documented tumor regression. All patients are treated on a linear accelerator. All patients receive the DEHART radiation regimen with concurrent and adjuvant monthly atezolizumab for 1 year. Atezolizumab (1680 mg) is delivered on the first day of radiation and every 4 weeks thereafter for up to 1 year after treatment. The primary endpoint of the study is the MTD of DEHART determined using a modified Time-To-Event Continual Reassessment Methodology (TITE-CRM). The MTD is the radiation dose at which there is a 30% rate of dose-limiting toxicity (DLT) up to 12 months after completion of radiation therapy. DLTs include an inability to complete radiation within 30 days of starting radiation deemed not to be related to disease progression and any Grade 4+ toxicity probably or definitely related to treatment with radiation and/or atezolizumab. Secondary study endpoints include locoregional control, overall survival, and patient quality-of-life as measured by the MD Anderson Symptom Inventory for Head and Neck (MDASI-HN) and the MD Anderson Dysphagia Inventory (MDADI-HN). <h3>Results</h3> TBD <h3>Conclusion</h3> TBD

Combining Serial and Parallel Functionality in Functional Lung Avoidance Radiation Therapy

Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury. Here, we compare the performance of FLA and FWAS and propose a novel method combining both approaches. We used breath-hold computed tomography (BHCT) and simulation 4-dimensional computed tomography (4DCT) from 12 lung stereotactic ablative radiation therapy patients. Four planning strategies were examined: (1) Conventional: no sparing other than clinical dose-volume constraints; (2) FLA: using a 4DCT-based ventilation map to delineate the HFL, plans were optimized to reduce mean dose and V13.50 in HFL; (3) FWAS: we autosegemented 11 to 13 generations of individual airways from each patient's BHCT and assigned priorities based on the relative contribution of each airway to total ventilation. We used these priorities in the optimization along with airway dose constraints, estimated as a function of airway diameter and 5% probability of collapse; and (4) FLA+FWAS: we combined information from the 2 strategies. We prioritized clinical dose constraints for organs at risk and planning target volume in all plans. We performed the evaluation in terms of ventilation preservation accounting for radiation-induced damage to both lung parenchyma and airways. We observed average ventilation preservation for FLA, FWAS, and FLA+FWAS as 3%, 8.5%, and 14.5% higher, respectively, than for Conventional plans for patients with ventilation preservation in Conventional plans <90%. Generalized estimated equations showed that all improvements were statistically significant (P ≤ .036). We observed no clinically relevant improvements in outcomes of the sparing techniques in patients with ventilation preservation in Conventional plans ≥90%. These initial results suggest that it is crucial to consider the parallel and the serial nature of the lung to improve post-radiation therapy lung function and, consequently, quality of life for patients.

Single-Fraction Celiac Plexus Radiosurgery: A Preliminary Proof-of-Concept Phase 2 Clinical Trial

Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate this pain. We performed a single-arm prospective clinical trial (ClinicalTrials.gov identifier: NCT02356406). Eligible and evaluable patients had celiac pain of at least 5 out of 10 on the Numerical Rating Scale, completed treatment per protocol, and had at least 1 posttreatment visit. The entire retroperitoneal celiac plexus was irradiated with a single 25-Gy fraction. The primary endpoint was change in the Numerical Rating Scale 3 weeks posttreatment. Toxic effects and pain interference (as measured with the Brief Pain Inventory) were secondary endpoints. For our study, 31 patients signed consent, and, of these, 18 patients were treated and evaluable. Median age was 68 years (range, 51-79); 89% of the patients had pancreatic cancer; the median Eastern Cooperative Oncology Group performance status was 1; and the median interval from initial diagnosis to treatment was 9 months (range, 1-36), and, in this interval, patients received a median of 1 systemic treatment line (range, 0-3). Acute toxicity was limited to grade 1 to 2. Three weeks after treatment, 16 patients (84%) reported decreased celiac pain, with median pain level falling from 6 out of 10 (interquartile range [IQR], 5.0-7.5) at baseline to 3 out of 10 (IQR, 1.0-4.3); six weeks after treatment, the Numerical Rating Scale number fell further to 2.8 out of 10 (IQR, 0-3.3; both P < .005 vs baseline), including 4 patients who reported complete eradication of their celiac pain. Total daily morphine milligram equivalents decreased from 59 pretreatment to 50 at 3 weeks, and from 50 to 45 at 6 weeks. Significant improvement was seen in pain-interference scores. Celiac plexus radiosurgery appears to alleviate cancer-related pain. An international multicenter phase 2 trial is currently accruing.

The First Use of Stereotactic Ablative Body Radiotherapy (SABR) in Extra-cranial Non-lung Oligometastatic Disease: A Single Centre

The First Use of Stereotactic Ablative Body Radiotherapy (SABR) in Extra-cranial Non-lung Oligometastatic Disease: A Single Centre

Narrative Review of High-Dose-Rate Interstitial Brachytherapy in Primary or Secondary Liver Tumors.

The optimal management of intrahepatic malignancies involves a multidisciplinary approach. Although surgical resection has been considered the only curative approach, the use of several minimally invasive ablative techniques has dramatically increased the last two decades, mainly due to the fact that they provide similar oncological results with significantly decreased morbidity. Among these modalities, interstitial liver brachytherapy, probably the most flexible liver ablative method, with excellent clinical data on its safety and effectiveness, is frequently not even mentioned as an option in the current peer reviewed literature and guidelines. Brachytherapy is a type of radiotherapy utilizing radionuclides that are directly inserted into the tumor. Compared to external beam radiation therapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time, with the advantage of a rapid dose fall-off, that allows for sparing of adjacent healthy tissue. For numerous malignancies such as skin, gynecological, breast, prostate, head and neck, bladder, liver and soft-tissue tumors, brachytherapy as a monotherapy or combined with external beam radiation therapy, has become a standard treatment for many decades. This review article aims to describe the high-dose-rate liver brachytherapy technique, its selection criteria, present its advantages and disadvantages, as well as the available clinical data, in order to help physicians to explore and hopefully introduce liver brachytherapy into their clinical routine.

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor: A new paradigm?

Stereotactic ablative body radiotherapy (SABR) is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer (NSCLC) and pulmonary metastasis. Several fractionation schemes have proven to be safe and effective, including the single fraction (SF) scheme. SF is an option cost-effectiveness, more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments. The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm, recommending this option to minimize patients’ visits to hospital. SF SABR already has a long experience, strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases, making it a valid treatment option; although its use in central locations, synchronous and recurrencies tumors requires more prospective safety and efficacy studies. The SABR radiobiology study, together with the combination with systemic therapies, (targeted therapies and immunotherapy) is a direction of research in both advanced disease and early stages whose future includes SF.

Curative intent Stereotactic Ablative Radiation Therapy (SABR) for treatment of lung oligometastases from head and neck squamous cell carcinoma (HNSCC): a multi-institutional retrospective study.

The aim of this retrospective study was to assess outcomes of SABR for metachronous isolated lung oligometastases from HNSCC. For patients who developed isolated, 1 or 2 lungs lesions (<5cm) consistent with metastases from HNSCC, the indication of SABR was validated in a multidisciplinary tumor board. All patients were monitored by CT or PET CT after SABR (Stereotactic Ablative Body Radiation) for HNSCC. Between November 2007 and February 2018, 52 patients were treated with SABR for metachronous lung metastases. The median time from the treatment of the primary HNSCC to the development of lung metastases was 18 months (3-93). The cohort's median age was 65.5 years old (50-83). The vast majority (94.2%) received 60 Gy in three fractions. Forty-one patients (78.5%) presented a solitary lung metastasis, while 11 patients (21.5%) had two lung metastases. With a median follow-up of 45.3 months, crude local and metastatic control rates were 74 and 38%, respectively. 1 year and 2 year Overall Survival (OS) were 85.8 and 65.9%, respectively. The median OS was 46.8 months. About one-fourth of patients were retreated by SABR for distant pulmonary recurrence. The treatment was well tolerated with only one patient who reported ≥ grade 3 toxicity (1.9%). In selected metastatic HNSCC patients, early detection and treatment of lung metastases with SABR is effective and safe. Prospective studies are required to validate this potential shift. Patients with oligometastases and controlled primary HNSCC seem to benefit from metastasis directed therapies.

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer.

PurposeStereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions.Methods and MaterialsThis study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally important difference (MID) assessing patient-reported quality of life was defined as greater than a one-half standard deviation increase in American Urological Association (AUA) symptom score after SAbR.ResultsTwo-hundred and forty-nine (249) low-, intermediate-, and high-risk PCa patients with median follow-up of 14.9 months for clinical toxicity were included. Acute urinary grade II toxicity occurred in 20.4% of patients. Acute grade II GI toxicity occurred in 7.3% of patients. For follow-up > 2 years (n = 69), late GU and GI grade ≥III toxicity occurred in 5.8% and 1.5% of patients, respectively. MID was evident in 31.8%, 23.4%, 35.8%, 37.0%, 33.3%, and 26.7% of patients at 3, 6, 12, 24, 36, and 48 months, respectively. The median follow-up for biochemical recurrence was 22.6 months with biochemical failure-free survival of 100% at 1 year (n = 226) and 98.7% for years 2 (n = 113) and 3 (n = 54).ConclusionsSAbR for PCa at 45 Gy in 5 fractions shows an encouraging safety profile. Prospective studies with longer follow-up are warranted to establish this dose regimen as standard of care for PCa.