The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC.

Purpose: To explore the association of the effective dose to immune cells (EDIC) with disease control, lymphopenia, and toxicity in patients with non-small cell lung cancer (NSCLC) and identify methods to reduce EDIC.

Methods: We abstracted data from all patients with locally advanced NSCLC treated with chemoradiation with or without consolidative immunotherapy over a ten-year period. Associations between EDIC and progression-free survival (PFS) and overall survival (OS) were modeled with Cox proportional hazards and Kaplan-Meier method.

Pneumonitis Rates Before and After Adoption of Immunotherapy Consolidation in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiation.

Purpose: We hypothesized that after adoption of immune checkpoint inhibitor (ICI) consolidation for patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiation therapy (cCRT), rates of symptomatic pneumonitis would increase, thereby supporting efforts to reduce lung radiation dose.

Methods And Materials: This single institution, multisite retrospective study included 783 patients with LA-NSCLC treated with definitive cCRT either before introduction of ICI consolidation (pre-ICI era cohort [January 2011-September 2017]; N = 448) or afterward (ICI era cohort [October 2017-December 2021]; N = 335). Primary endpoint was grade ≥2 pneumonitis (G2P) and secondary endpoint was grade ≥3 pneumonitis (G3P), per Common Terminology Criteria for Adverse Events v5.

Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging in Radiation Therapy Treatment Planning: A Review of PET Imaging Tracers and Methods to Incorporate PET/CT.

Purpose: Positron emission tomography (PET)/computed tomography (CT) has become a critical tool in clinical oncology with an expanding role in guiding radiation treatment planning. As its application and availability grows, it is increasingly important for practicing radiation oncologists to have a comprehensive understanding of how molecular imaging can be incorporated into radiation planning and recognize its potential limitations and pitfalls. The purpose of this article is to review the major approved positron-emitting radiopharmaceuticals clinically being used today along with the methods used for their integration into radiation therapy including methods of image registration, target delineation, and emerging PET-guided protocols such as biologically-guided radiation therapy and PET-adaptive therapy.

A comparative study of machine-learning approaches in proton radiography using energy-resolved dose function.

Purpose: The feasibility of machine learning (ML) techniques and their performance compared to the conventional χ-minimization technique in the context of the proton energy-resolved dose imaging method are presented.

Materials And Method: Various geometries resembling a wedge and varying gradients are simulated in GATE to obtain energy-resolved dose functions (ERDF) from proton beams of different energies. These ERDFs are used to predict the WEPL using a conventional technique and other ML-based methods.

A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.

Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning.

Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation.

Dosimetric Results for Adjuvant Proton Radiation Therapy of HPV-Associated Oropharynx Cancer.

Purpose: One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC.

Materials And Methods: This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019.

Tubarial salivary gland sparing with proton therapy.

The recently identified bilateral macroscopic tubarial salivary glands present a potential opportunity for further toxicity mitigation for patients receiving head and neck radiotherapy. Here, we show superior dosimetric sparing of the tubarial salivary glands with proton radiation therapy (PRT) compared to intensity-modulated radiotherapy (IMRT) for patients treated postoperatively for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019.

Stricter Postoperative Oropharyngeal Cancer Radiation Therapy Normal Tissue Dose Constraints Are Feasible.

Purpose: Although dose de-escalation is one proposed strategy to mitigate long-term toxicity in human papillomavirus associated oropharyngeal cancer, applying more stringent normal tissue constraints may be a complementary approach to further reduce toxicity. Our study demonstrates that in a postoperative setting, improving upon nationally accepted constraints is achievable and leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease control.

Methods And Materials: We identified 92 patients at our institution between 2015 and 2019 with p16+ oropharyngeal cancer who were treated with adjuvant volumetric modulated arc therapy.

A proof-of-concept study of an in-situ partial-ring time-of-flight PET scanner for proton beam verification.

Development of a PET system capable of imaging requires a design that can accommodate the proton treatment beam nozzle. Among the several PET instrumentation approaches developed thus far, the dual-panel PET scanner is often used as it is simpler to develop and integrate within the proton therapy gantry. Partial-angle coverage of these systems can however lead to limited-angle artefacts in the reconstructed PET image.

Dual-Energy Computed Tomography Proton-Dose Calculation with Scripting and Modified Hounsfield Units.

Purpose: To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calculation.

Materials And Methods: The DECT images were acquired at 80 kVp and 140 kVp and were processed with computed tomography scanner software to derive the electron density and effective atomic number images.

Current delivery limitations of proton PBS for FLASH.

Purpose: Proton Pencil Beam Scanning (PBS) is an attractive solution to realize the advantageous normal tissue sparing elucidated from FLASH high dose rates. The mechanics of PBS spot delivery will impose limitations on the effective field dose rate for PBS.

Methods: This study incorporates measurements from clinical and FLASH research beams on uniform single energy and the spread-out Bragg Peak PBS fields to extrapolate the PBS dose rate to high cyclotron beam currents 350, 500, and 800 nA.

Per-fraction positional and dosimetric performance of prone breast tangential radiotherapy on Halcyon™ linear accelerator assessed with daily rapid kilo-voltage cone beam computed tomography: a single-institution pilot study.

Background: This study investigates daily breast geometry and delivered dose to prone-positioned patients undergoing tangential whole breast radiation therapy (WBRT) on an O-ring linear accelerator with 6X flattening filter free mode (6X-FFF), planned with electronic compensation (ECOMP) method. Most practices rely on skin marks or daily planar image matching for prone breast WBRT. This system provides low dose daily CBCT, which was used to study daily robustness of delivered dose parameters for prone-positioned WBRT.

Higher Dose Volumes May Be Better for Evaluating Radiation Pneumonitis in Lung Proton Therapy Patients Compared With Traditional Photon-Based Dose Constraints.

Purpose: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy.

Methods And Materials: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified.

Feasibility of energy-resolved dose imaging technique in pencil beam scanning mode.

Proton energy-resolved dose imaging (pERDI) is a recently proposed technique to generate water equivalent path length (WEPL) images using a single detector. Owing to its simplicity in instrumentation, analysis and the possibility of using the in-room x-ray flat panels as detectors, this technique offers a promising avenue towards a clinically usable imaging system for proton therapy using scanned beams. The purpose of this study is to estimate the achievable accuracy in WEPL and Relative Stopping Power (RSP) using the pERDI technique and to assess the minimum dose required to achieve such accuracy.

Dose to Highly Functional Ventilation Zones Improves Prediction of Radiation Pneumonitis for Proton and Photon Lung Cancer Radiation Therapy.

Purpose: We hypothesized that the radiation dose in high-ventilation portions of the lung better predicts radiation pneumonitis (RP) outcome for patients treated with proton radiation therapy (PR) and photon radiation therapy (PH).

Methods And Materials: Seventy-four patients (38 protons, 36 photons) with locally advanced non-small cell lung cancer treated with concurrent chemoradiation therapy were identified, of whom 24 exhibited RP (graded using Common Terminology Criteria for Adverse Events v4.0) after PR or PH, and 50 were negative controls.

Inter-fraction robustness of intensity-modulated proton therapy in the post-operative treatment of oropharyngeal and oral cavity squamous cell carcinomas.

Objective: To evaluate dosimetric consequences of inter-fraction setup variation and anatomical changes in patients receiving multifield optimised (MFO) intensity modulated proton therapy for post-operative oropharyngeal (OPC) and oral cavity (OCC) cancers.

Methods: Six patients receiving MFO for post-operative OPC and OCC were evaluated. Plans were robustly optimised to clinical target volumes (CTVs) using 3 mm setup and 3.

Dosimetric Characterization of the Dual Layer MLC System for an O-Ring Linear Accelerator.

The Halcyon is Varian's latest linear accelerator that offers a single 6X flattening-filter-free beam with a jawless design that features a new dual layer multileaf collimator system with faster speed and reduced transmission. Dosimetric characteristics of the dual layer multileaf collimator system including transmission, dosimetric leaf gap, and tongue and groove effects were measured. Ionization chambers, diode arrays, and an electronic portal imaging device were used to measure various multileaf collimator characteristics.

A Super-Learner Model for Tumor Motion Prediction and Management in Radiation Therapy: Development and Feasibility Evaluation.

In cancer radiation therapy, large tumor motion due to respiration can lead to uncertainties in tumor target delineation and treatment delivery, thus making active motion management an essential step in thoracic and abdominal tumor treatment. In current practice, patients with tumor motion may be required to receive two sets of CT scans - the initial free-breathing 4-dimensional CT (4DCT) scan for tumor motion estimation and a second CT scan under appropriate motion management such as breath-hold or abdominal compression. The aim of this study is to assess the feasibility of a predictive model for tumor motion estimation in three-dimensional space based on machine learning algorithms.

Characterization of the Megavoltage Cone-Beam Computed Tomography (MV-CBCT) System on Halcyon for IGRT: Image Quality Benchmark, Clinical Performance, and Organ Doses.

The Varian Halcyon includes an ultrafast 6 MV flattening filter free (FFF) cone-beam computed tomography (MV-CBCT). Although a kV-CBCT add-on is available, in the basic configuration MV is used for image guided radiotherapy (IGRT). We characterized the MV-CBCT imager in terms of reproducibility, linearity, field of view (FOV) dependence, detectability of soft-tissue, and the effect of metal implants.

Multi-Institutional Dosimetric Evaluation of Modern Day Stereotactic Radiosurgery (SRS) Treatment Options for Multiple Brain Metastases.

There are several popular treatment options currently available for stereotactic radiosurgery (SRS) of multiple brain metastases: Co sources and cone collimators around a spherical geometry (GammaKnife), multi-aperture dynamic conformal arcs on a linac (BrainLab Elements™ v1.5), and volumetric arc therapy on a linac (VMAT) calculated with either the conventional optimizer or with the Varian HyperArc™ solution. This study aimed to dosimetrically compare and evaluate the differences among these treatment options in terms of dose conformity to the tumor as well as dose sparing to the surrounding normal tissues.

Spine SBRT With Halcyon™: Plan Quality, Modulation Complexity, Delivery Accuracy, and Speed.

Spine SBRT requires treatment plans with steep dose gradients and tight limits to the cord maximal dose. A new dual-layer staggered 1-cm MLC in Halcyon™ treatment platform has improved leakage, speed, and DLG compared to 120-Millennium (0.5-cm) and High-Definition (0.

Dosimetric Performance and Planning/Delivery Efficiency of a Dual-Layer Stacked and Staggered MLC on Treating Multiple Small Targets: A Planning Study Based on Single-Isocenter Multi-Target Stereotactic Radiosurgery (SRS) to Brain Metastases.

To evaluate the dosimetric performance and planning/delivery efficiency of a dual-layer MLC system for treating multiple brain metastases with a single isocenter. 10 patients each with 6-10 targets with volumes from 0.11 to 8.

Impact of Multi-leaf Collimator Parameters on Head and Neck Plan Quality and Delivery: A Comparison between Halcyon™ and Truebeam® Treatment Delivery Systems.

Purpose A new dual-layer multi-leaf collimator (MLC) system with several improved characteristics was introduced with the Varian Halcyon™ treatment platform. This study evaluated this new MLC's impact on head and neck plan quality and delivery efficiency. Methods Nine patients were retrospectively studied with Institutional Review Board (IRB) approval.

NCTN clinical trial standardization for radiotherapy through IROC and CIRO.

Evidence-based practice is the cornerstone of modern medicine. Randomized clinical trials across multiple institutions are the gold standard for modern evidence collection. National Cancer Trials Network (NCTN) instruments the clinical trials through the new infrastructure for improvements in cancer treatment.