•Histology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). ...Histology-driven SBRT approach has not been explored in routine clinic practice and histology-dependent fractionation schemes remain unknown.•We analyzed pooled histologic TCP data for early-stage NSCLC patients as a function of biologically effective dose (BED) and determined histology-driven optimal SBRT and hypofrationated radiation therapy schemes of least doses to maximize tumor control in 1–30 fractions for the two predominant histologic subtypes lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC).•The determined SBRT schemes are consistent with clinic practice for ADC, SCC requires substantially higher doses to maximize tumor control than ADC. These histology-driven optimal hypofractionated radiation therapy schemes provide first insights for personalized radiation therapy of two predominant early-stage NSCLC subtypes ADC and SCC.
Histology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiotherapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). A histology-driven SBRT approach has not been explored in routine clinical practice and histology-dependent fractionation schemes remain unknown. Here, we analyzed pooled histologic TCP data as a function of biologically effective dose (BED) to determine histology-driven fractionation schemes for SBRT and hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC).
The least-χ2 method was used to fit the collected histologic TCP data of 8510 early-stage NSCLC patients to determine parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative.
A fit to the histologic TCP data yielded independent radiobiological parameter sets for radiotherapy of early-stage lung ADC and SCC. TCP increases steeply with BED and reaches an asymptotic maximal plateau, allowing us to determine model-independent optimal fractionation schemes of least doses in 1–30 fractions to achieve maximal tumor control for early-stage lung ADC and SCC, e.g., 30, 44, 48, and 51 Gy for ADC, and 32, 48, 54, and 58 Gy for SCC in 1, 3, 4, and 5 fractions, respectively.
We presented the first determination of histology-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. These proposed optimal fractionation schemes provide first insights for histology-based personalized radiotherapy of two predominant early-stage NSCLC subtypes ADC and SCC, which require further validation with large-scale histologic TCP data.
A series of radiobiological models were developed to study tumor control probability (TCP) for stereotactic body radiation therapy (SBRT) of early-stage non-small cell lung cancer (NSCLC) per the ...Hypofractionated Treatment Effects in the Clinic (HyTEC) working group. This study was conducted to further validate 3 representative models with the recent clinical TCP data ranging from conventional radiation therapy to SBRT of early-stage NSCLC and to determine systematic optimal fractionation regimens in 1 to 30 fractions for radiation therapy of early-stage NSCLC that were found to be model-independent.
Recent clinical 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP data of 9808 patients from 56 published papers were collected for radiation therapy of 2 to 4 Gy per fraction and SBRT of early-stage NSCLC. This data set nearly triples the original HyTEC sample, which was used to further validate the HyTEC model parameters determined from a fit to the clinical TCP data.
TCP data from the expanded data set are well described by the HyTEC models with α/β ratios of about 20 Gy. TCP increases sharply with biologically effective dose and reaches an asymptotic maximal plateau, which allows us to determine optimal fractionation schemes for radiation therapy of early-stage NSCLC.
The HyTEC radiobiological models with α/β ratios of about 20 Gy determined from the fits to the clinical TCP data for SBRT of early-stage NSCLC describe the recent TCP data well for both radiation therapy of 2 to 4 Gy per fraction and SBRT dose and fractionation schemes of early-stage NSCLC. A steep dose response exists between TCP and biologically effective dose, and TCP reaches an asymptotic maximum. This feature results in model-independent optimal fractionation regimens determined whenever safe for SBRT and hypofractionated radiation therapy of early-stage NSCLC in 1 to 30 fractions to achieve asymptotic maximal tumor control, and T2 tumors require slightly higher optimal doses than T1 tumors. The proposed optimal fractionation schemes are consistent with clinical practice for SBRT of early-stage NSCLC.
Purpose
To examine the response properties of cylindrical cavity ionization chambers (ICs) in the depth‐ionization buildup region so as to obtain a robust chamber‐signal — based method for definitive ...water surface identification, hence absolute ionization chamber depth localization.
Method & materials
An analytical model with simplistic physics and geometry is developed to explore the theoretical aspects of ionization chamber response near a phantom water surface. Monte Carlo simulations with full physics and ionization chamber geometry are utilized to extend the model's findings to realistic ion chambers in realistic beams and to study the effects of IC design parameters on the entrance dose response. Design parameters studied include full and simplified IC designs with varying central electrode thickness, wall thickness, and outer chamber radius. Piecewise continuous fits to the depth‐ionization signal gradient are used to quantify potential deviation of the gradient discontinuity from the chamber outer radius. Exponential, power, and hyperbolic sine functional forms are used to model the gradient for chamber depths of zero to the depth of the gradient discontinuity.
Results
The depth‐ionization gradient as a function of depth is maximized and discontinuous when a submerged IC's outer radius coincides with the water surface. We term this depth the gradient chamber alignment point (gCAP). The maximum deviation between the gCAP location and the chamber outer radius is 0.13 mm for a hypothetical 4 mm thick wall, 6.45 mm outer radius chamber using the power function fit, however, the chamber outer radius is within the 95% confidence interval of the gCAP determined by this fit. gCAP dependence on the chamber wall thickness is possible, but not at a clinically relevant level.
Conclusions
The depth‐ionization gradient has a discontinuity and is maximized when the outer‐radius of a submerged IC coincides with the water surface. This feature can be used to auto‐align ICs to the water surface at the time of scanning and/or be applied retrospectively to scan data to quantify absolute IC depth. Utilization of the gCAP should yield accurate and reproducible depth calibration for clinical depth‐ionization measurements between setups and between users.
Background
To describe intensity‐modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose‐limiting structures.
...Methods
Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease‐specific survival were estimated using the Kaplan Meier method.
Results
Twenty patients were included. Nineteen patients had T3‐4 tumors. Median follow‐up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2‐year OS was 94.7% (95% CI: 85.2%–100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy‐proven.
Conclusions
IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.
Purpose
The purpose of this study was to experimentally examine the reliability of the gradient chamber alignment point (gCAP) determination method for accurately identifying water surface location ...with a range of ionization chambers (ICs).
Materials and methods
Twelve cylindrical ICs were scanned from depth through a water surface into air using a customized high‐accuracy scanning system which allows for accurate alignment of the IC with respect to the true water surface. Thirteen other cylindrical ICs and five parallel‐plate ICs were scanned using a standard commercially available scanning system. The thirty different ICs used in this study represent 22 different IC models. Measurements were taken with different radiation field parameters such as incident photon beam energies and field sizes. The effects of scan direction and water surface tension were also investigated. The depth at which the gradient of the relative ionization was maximized and discontinuous, the gCAP, was found for each curve. Each measured gCAP depth was compared with the theoretically expected gCAP location, the depth at which the submerged IC outer radius (OR) coincides with the water surface.
Results
When scanning an IC from in water to air, the only parameter that affects the gCAP location is the IC OR. The gCAP location corresponds with the IC central axis positioned at a depth equal to the IC OR within the 0.1 mm measurement scan resolution for all eighteen ICs studied with the commercially available system. Using the customized scanning system, all but three ICs were identified exhibiting a gCAP within the scan resolution, with the other three within 0.25 mm of the expected location. This discrepancy was not observed in the same IC model when using the conventional scanning system. Altering the beam energy from 6 to 25 MV did not alter the gCAP location, nor did variations in the radiation field size or scan parameters. In‐air IC response is proportional to the IC wall thickness.
Conclusion
The water‐to‐air scanning method coupled with gCAP analysis identifies the alignment of the IC OR to the water surface within the scanning resolution for all ICs studied. The gCAP method can precisely and reproducibly align the physical center of a given cylindrical IC with the water surface, be applied prospectively or retrospectively, and provides the prospect for automated water surface identification for scanning systems. The gCAP method eliminates the visual subjectivity inherent to current IC‐to‐water surface alignment techniques, has been validated with a wide variety of commercially available ICs, and should be independent of the scanning system used for data acquisition.
Organic dosimeters offer unique advantages over traditional technologies, and they can be used to expand the capabilities of current radiation detection systems. In-depth knowledge of the mechanisms ...underlying the interaction between radiation and organic materials is essential for their widespread adoption. Here, we identified and quantitatively characterized the electronic traps generated during the operation of radiation dosimeters based on organic field-effect transistors. Spectral analysis of the trap density of states, along with optical and structural studies, revealed the origin of trap states as local structural disorder within the crystalline films. Our results provide new insights into the radiation-induced defects in organic dosimeters, and pave the way for the development of more efficient and reliable radiation detection devices.
An investigation into the origins of radiation-generated traps utilizing characterization of large area transistor arrays, spectral analysis of the trap density of states, photoluminescence spectroscopy, and GIWAXS.
Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests.
In this single ...institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score.
Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes.
Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future.
Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation.
Epidural disease closer than 3 mm from the spinal cord is sometimes regarded as a contraindication to spine radiosurgery (SRS) or stereotactic body radiotherapy (SBRT). Current guidelines on the ...management of high-grade epidural disease recommend surgical decompression followed by conventionally fractionated external-beam radiotherapy (EBRT) or post-operative SBRT
1
,
2
. For patients with high-grade epidural disease who are medically inoperable, conventional EBRT is typically recommended, even though clinical response rates are lower and durability is limited
3
. A few expert centers use decompressive SRS in a single fraction for high-grade epidural disease
4
,
5
, but this technique has not been incorporated into treatment algorithms such as the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework
1
,
2
. Here we present a case where five-fraction SBRT followed by immunotherapy resulted in a complete radiographic and clinical response for a patient with epidural disease that was compressing the thecal sac. We compare the radiographic response in this patient to data in a prior publication that quantified the improvement in thecal sac patency after decompressive SRS, and we suggest that current treatment algorithms need to be updated in the era of immunotherapy.
Abstract
Background
Re-irradiation for recurrent gliomas is a controversial treatment option with no clear standard dose or concurrent systemic therapy.
Methods
This series represents a ...single-institution retrospective review of patients treated with re-irradiation for recurrent high-grade glioma. After 2012, patients were commonly offered concurrent bevacizumab as a cytoprotective agent against radiation necrosis. Kaplan-Meier method was used to estimate overall survival and progression-free survival. Cox proportional hazards regression was used to identify factors associated with overall survival and progression-free survival.
Results
Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P < .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15).
Conclusion
High dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma.
