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1.
Acta Oncol ; 56(4): 531-540, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28358666

RESUMO

BACKGROUND: For lung tumors with large motion amplitudes, the use of proton pencil beam scanning (PBS) can produce large dose errors. In this study, we assess under what circumstances PBS can be used to treat lung cancer patients who exhibit large tumor motion, based on the quantification of tumor motion and the dose interplay. MATERIAL AND METHODS: PBS plans were optimized on average 4DCT datasets using a beam-specific PTV method for 10 consecutive patients with locally advanced non-small-cell-lung-cancer (NSCLC) treated with proton therapy to 6660/180 cGy. End inhalation (CT0) and end exhalation (CT50) were selected as the two extreme scenarios to acquire the relative stopping power ratio difference (Δrsp) for a respiration cycle. The water equivalent difference (ΔWET) per radiological path was calculated from the surface of patient to the iCTV by integrating the Δrsp of each voxel. The magnitude of motion of voxels within the target follows a quasi-Gaussian distribution. A motion index (MI (>5mm WET)), defined as the percentage of target voxels with an absolute integral ΔWET larger than 5 mm, was adopted as a metric to characterize interplay. To simulate the treatment process, 4D dose was calculated by accumulating the spot dose on the corresponding respiration phase to the reference phase CT50 by deformable image registration based on spot timing and patient breathing phase. RESULTS: The study indicated that the magnitude of target underdose in a single fraction plan is proportional to the MI (p < .001), with larger motion equating to greater dose degradation and standard deviations. The target homogeneity, minimum, maximum and mean dose in the 4D dose accumulations of 37 fractions varied as a function of MI. CONCLUSIONS: This study demonstrated that MI can predict the level of dose degradation, which potentially serves as a clinical decision tool to assess whether lung cancer patients are potentially suitable to receive PBS treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Artefatos , Fracionamento da Dose de Radiação , Tomografia Computadorizada Quadridimensional , Humanos , Movimento (Física) , Movimento
2.
J Appl Clin Med Phys ; 18(1): 107-114, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28291918

RESUMO

PURPOSE/OBJECTIVE(S): High-risk neuroblastoma (HR-NBL) requires multimodality treatment, including external beam radiation of the primary tumor site following resection. Radiotherapy planning must take into account motion of the target and adjacent normal anatomy, both of which are poorly understood in the pediatric population, and which may differ significantly from those in adults. METHODS/MATERIALS: We examined 4DCT scans of 15 consecutive pediatric patients treated for HR-NBL, most with tumors in the abdominal cavity. The diaphragm and organs at risk were contoured at full inhale, full exhale, and on free-breathing scans. Maximum displacement of organs between full inhale and full exhale was measured in the anterior, posterior, superior, inferior, left, and right directions, as was displacement of centroids in the A/P, S/I, and L/R axes. Contours on free-breathing scans were compared to those on 4D scans. RESULTS: Maximum displacement was along the S/I axis, with the superior aspects of organs moving more than the inferior, implying organ compression with respiration. Liver and spleen exhibited the largest motion, which correlated strongly with the S/I motion of the diaphragm. The maximum organ motion observed in the abdomen and thorax were 4.5 mm and 7.4 mm, respectively, while maximum diaphragm displacement was 5.7 mm. Overall findings mirrored observations in adults, but with smaller magnitudes, as expected. No consistent margins could be added to the free-breathing scans to encompass the motion determined using 4DCT. CONCLUSIONS: Organ motion within the pediatric abdomen and pelvis is similar to that observed in adults, but with smaller magnitude. Precise margins to accommodate motion are patient-specific, underscoring the need for 4DCT scanning when possible.


Assuntos
Tomografia Computadorizada Quadridimensional/métodos , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/radioterapia , Órgãos em Risco/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Criança , Pré-Escolar , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Lactente , Masculino , Movimento (Física) , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Respiração , Fatores de Risco
3.
J Appl Clin Med Phys ; 17(2): 427-440, 2016 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-27074464

RESUMO

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Processamento de Imagem Assistida por Computador/métodos , Terapia com Prótons , Água/química , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estadiamento de Neoplasias , Aceleradores de Partículas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos
4.
J Appl Clin Med Phys ; 16(3): 4959, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-26103473

RESUMO

In electron and proton radiotherapy, applications of patient-specific electron bolus or proton compensators during radiation treatments are often necessary to accommodate patient body surface irregularities, tissue inhomogeneity, and variations in PTV depths to achieve desired dose distributions. Emerging 3D printing technologies provide alternative fabrication methods for these bolus and compensators. This study investigated the potential of utilizing 3D printing technologies for the fabrication of the electron bolus and proton compensators. Two printing technologies, fused deposition modeling (FDM) and selective laser sintering (SLS), and two printing materials, PLA and polyamide, were investigated. Samples were printed and characterized with CT scan and under electron and proton beams. In addition, a software package was developed to convert electron bolus and proton compensator designs to printable Standard Tessellation Language file format. A phantom scalp electron bolus was printed with FDM technology with PLA material. The HU of the printed electron bolus was 106.5 ± 15.2. A prostate patient proton compensator was printed with SLS technology and polyamide material with -70.1 ± 8.1 HU. The profiles of the electron bolus and proton compensator were compared with the original designs. The average over all the CT slices of the largest Euclidean distance between the design and the fabricated bolus on each CT slice was found to be 0.84 ± 0.45 mm and for the compensator to be 0.40 ± 0.42 mm. It is recommended that the properties of specific 3D printed objects are understood before being applied to radiotherapy treatments.


Assuntos
Elétrons , Impressão Tridimensional/instrumentação , Prótons , Radioterapia Conformacional/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Estudos de Viabilidade , Espalhamento de Radiação
5.
J Appl Clin Med Phys ; 15(5): 4851, 2014 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-25207571

RESUMO

Head and neck cancers centered at the base of skull are better visualized on MRI than on CT. The purpose of this investigation was to investigate the accuracy of bulk density assignment in head and neck intensity-modulated radiation therapy (IMRT) treatment plan optimization. Our study investigates dose calculation differences between density-assigned MRI and CT, and identifies potential limitations related to dental implants and MRI geometrical distortion in the framework of MRI-only-based treatment planning. Bulk density assignment was performed and applied onto MRI to generate three MRI image sets with increasing levels of heterogeneity for seven patients: 1) MRIW: all water-equivalent; 2) MRIW+B: included bone with density of 1.53 g/cm3; and 3) MRIW+B+A: included bone and air. Using identical planning and optimization parameters, MRI-based IMRT plans were generated and compared to corresponding, forward-calculated, CT-based plans on the basis of target coverage, isodose distributions, and dose-volume histograms (DVHs). Phantom studies were performed to assess the magnitude and spatial dependence of MRI geometrical distortion. MRIW-based dose calculations overestimated target coverage by 16.1%. Segmentation of bone reduced differences to within 2% of the coverage area on the CT-based plan. Further segmentation of air improved conformity near air-tissue interfaces. Dental artifacts caused substantial target coverage overestimation even on MRIW+B+A. Geometrical distortion was less than 1 mm in an imaging volume 20 × 20 × 20 cm3 around scanner isocenter, but up to 4 mm at 17 cm lateral to isocenter. Bulk density assignment in the framework of MRI-only IMRT head and neck treatment planning is a feasible method with certain limitations. Bone and teeth account for the majority of density heterogeneity effects. While soft tissue is well visualized on MRI compared to CT, dental implants may not be visible on MRI and must be identified by other means and assigned appropriate density for accurate dose calculation. Far off-center geometrical distortion of the body contour near the shoulder region is a potential source of dose calculation inaccuracy.


Assuntos
Algoritmos , Neoplasias Nasofaríngeas/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Adulto , Carcinoma , Estudos de Viabilidade , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Med Phys ; 51(7): 5081-5093, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38597815

RESUMO

BACKGROUND: Cyclotron-based proton therapy systems utilize the highest proton energies to achieve an ultra-high dose rate (UHDR) for FLASH radiotherapy. The deep-penetrating range associated with this high energy can be modulated by inserting a uniform plate of proton-stopping material, known as a range shifter, in the beam path at the nozzle to bring the Bragg peak within the target while ensuring high proton transport efficiency for UHDR. Aluminum has been recently proposed as a range shifter material mainly due to its high compactness and its mechanical properties. A possible drawback lies in the fact that aluminum has a larger cross-section of producing secondary neutrons compared to conventional plastic range shifters. Accordingly, an increase in secondary neutron contamination was expected during the delivery of range-modulated FLASH proton therapy, potentially heightening neutron-induced carcinogenic risks to the patient. PURPOSE: We conducted neutron dosimetry using simulations and measurements to evaluate excess dose due to neutron exposure during UHDR proton irradiation with aluminum range shifters compared to plastic range shifters. METHODS: Monte Carlo simulations in TOPAS were performed to investigate the secondary neutron production characteristics with aluminum range shifter during 225 MeV single-spot proton irradiation. The computational results were validated against measurements with a pair of ionization chambers in an out-of-field region ( ≤ $\le$ 30 cm) and with a Proton Recoil Scintillator-Los Alamos rem meter in a far-out-of-field region (0.5-2.5 m). The assessments were repeated with solid water slabs as a surrogate for the conventional range shifter material to evaluate the impact of aluminum on neutron yield. The results were compared with the International Electrotechnical Commission (IEC) standards to evaluate the clinical acceptance of the secondary neutron yield. RESULTS: For a range modulation up to 26 cm in water, the maximum simulated and measured values of out-of-field secondary neutron dose equivalent per therapeutic dose with aluminum range shifter were found to be ( 0.57 ± 0.02 ) mSv/Gy $(0.57\pm 0.02)\ \text{mSv/Gy}$ and ( 0.46 ± 0.04 ) mSv/Gy $(0.46\pm 0.04)\ \text{mSv/Gy}$ , respectively, overall higher than the solid water cases (simulation: ( 0.332 ± 0.003 ) mSv/Gy $(0.332\pm 0.003)\ \text{mSv/Gy}$ ; measurement: ( 0.33 ± 0.03 ) mSv/Gy $(0.33\pm 0.03)\ \text{mSv/Gy}$ ). The maximum far out-of-field secondary neutron dose equivalent was found to be ( 8.8 ± 0.5 $8.8 \pm 0.5$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ and ( 1.62 ± 0.02 $1.62 \pm 0.02$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ for the simulations and rem meter measurements, respectively, also higher than the solid water counterparts (simulation: ( 3.3 ± 0.3 $3.3 \pm 0.3$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ ; measurement: ( 0.63 ± 0.03 $0.63 \pm 0.03$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ ). CONCLUSIONS: We conducted simulations and measurements of secondary neutron production under proton irradiation at FLASH energy with range shifters. We found that the secondary neutron yield increased when using aluminum range shifters compared to conventional materials while remaining well below the non-primary radiation limit constrained by the IEC regulations.


Assuntos
Método de Monte Carlo , Nêutrons , Terapia com Prótons , Radiometria , Terapia com Prótons/instrumentação , Radiometria/instrumentação , Radioterapia Conformacional/instrumentação , Radioterapia Conformacional/métodos , Alumínio/química , Dosagem Radioterapêutica , Humanos
7.
Radiother Oncol ; 190: 110030, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38008414

RESUMO

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. Logistic regression was used to model predictors of lymphopenia and higher EDIC. Analyses were performed with EDIC as a continuous and categorical variable. Lymphopenia was graded per CTCAE v5.0. RESULTS: Overall, 786 patients were included (228 of which received consolidative immunotherapy); median EDIC was 4.7 Gy. Patients with EDIC < 4.7 Gy had a longer median PFS (15.3 vs. 9.0 months; p < 0.001) and OS (34.2 vs. 22.4 months; p < 0.001). On multivariable modeling, EDIC correlated with inferior PFS (HR 1.08, 95 % CI 1.01-1.14, p = 0.014) and OS (HR 1.10, 95 % CI 1.04-1.18, p = 0.002). EDIC was predictive of grade 4 lymphopenia (OR 1.16, 95 % CI 1.02-1.33, p = 0.026). EDIC ≥ 4.7 Gy was associated with increased grade 2 + pneumonitis (6-month incidence: 26 % vs 20 %, p = 0.04) and unplanned hospitalizations (90-day incidence: 40 % vs 30 %, p = 0.002). Compared to protons, photon therapy was associated with EDIC ≥ 4.7 Gy (OR 5.26, 95 % CI 3.71-7.69, p < 0.001) in multivariable modeling. CONCLUSIONS: EDIC is associated with inferior disease outcomes, treatment-related toxicity, and the development of severe lymphopenia. Proton therapy is associated with lower EDIC. Further investigations to limit radiation dose to the immune system appear warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfopenia , Humanos , Linfopenia/etiologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Doses de Radiação
8.
Int J Radiat Oncol Biol Phys ; 118(5): 1445-1454, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37619788

RESUMO

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 v5.0. Pneumonitis was compared between pre-ICI era and ICI era cohorts using the cumulative incidence function and Gray's test. Inverse probability of treatment weighting (IPTW)-adjusted Fine-Gray models were generated. Logistic models were developed to predict the 1-year probability of G2P as a function of lung dosimetry. RESULTS: G2P was higher in the ICI era than in the pre-ICI era (1-year cumulative incidence 31.4% vs 20.1%; P < .001; IPTW-adjusted multivariable subdistribution hazard ratio, 2.03; 95% confidence interval, 1.53-2.70; P < .001). There was no significant interaction between ICI era treatment and either lung volume receiving ≥20 Gy (V20) or mean lung dose in Fine-Gray regression for G2P; however, the predicted probability of G2P was higher in the ICI era at clinically relevant values of lung V20 (≥24%) and mean lung dose (≥14 Gy). Cut-point analysis revealed a lung V20 threshold of 28% in the ICI era (1-year G2P rate 46.0% above vs 19.8% below; P < .001). Among patients receiving ICI consolidation, lung V5 was not associated with G2P. G3P was not higher in the ICI era (1-year cumulative incidence 7.5% vs 6.0%; P = .39; IPTW-adjusted multivariable subdistribution hazard ratio, 1.12; 95% confidence interval, 0.63-2.01; P = .70). CONCLUSIONS: In patients with LA-NSCLC treated with cCRT, the adoption of ICI consolidation was associated with an increase in G2P but not G3P. With ICI consolidation, stricter lung dose constraints may be warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Estudos Retrospectivos , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/epidemiologia , Imunoterapia/efeitos adversos
9.
Phys Med ; 106: 102525, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36621081

RESUMO

PURPOSE: The feasibility of machine learning (ML) techniques and their performance compared to the conventional χ2-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. The results are compared to gain an understanding of the performance of ML models in proton radiography. RESULTS: The results obtained from the χ2-minimization technique indicate that it is robust and more reliable compared to the ML-based techniques. It is also observed that the ML-based techniques did not mitigate the effect of range-mixing but seem to be more affected by it compared to the χ2-minimization technique. Substantial data reduction was required in order to make the results of ML-based methods comparable to that of χ2-minimization. We also note that such data reduction might not be possible in a clinical setting. The only advantage in using the ML-based technique is the computational time required to generate a WEPL map which, in our case study, is 10-30 times shorter than the time required for the conventional χ2-minimization technique. CONCLUSIONS: The first results from this preliminary study indicate that the ML techniques failed to be on par with the conventional χ2-minimization technique in terms of the achievable accuracy in the predictions of WEPL and in the mitigation of range-mixing effects in the WEPL image. Modern strategies like the GAN-based models may be suitable for such applications.


Assuntos
Terapia com Prótons , Prótons , Radiografia , Aprendizado de Máquina , Terapia com Prótons/métodos
10.
Adv Radiat Oncol ; 8(5): 101212, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197709

RESUMO

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. Methods and Materials: A review approach was utilized using collective information from a broad review of the existing scientific literature sourced from PubMed search with relevant keywords and input from a multidisciplinary team of experts in medical physics, radiation treatment planning, nuclear medicine, and radiation therapy. Results: A number of radiotracers imaging various targets and metabolic pathways of cancer are now commercially available. PET/CT data can be incorporated into radiation treatment planning through cognitive fusion, rigid registration, deformable registration, or PET/CT simulation techniques. PET imaging provides a number of benefits to radiation planning including improved identification and delineation of the radiation targets from normal tissue, potential automation of target delineation, reduction of intra- and inter-observer variability, and identification of tumor subvolumes at high risk for treatment failure which may benefit from dose intensification or adaptive protocols. However, PET/CT imaging has a number of technical and biologic limitations that must be understood when guiding radiation treatment. Conclusion: For PET guided radiation planning to be successful, collaboration between radiation oncologists, nuclear medicine physicians, and medical physics is essential, as well as the development and adherence to strict PET-radiation planning protocols. When performed properly, PET-based radiation planning can reduce treatment volumes, reduce treatment variability, improve patient and target selection, and potentially enhance the therapeutic ratio accessing precision medicine in radiation therapy.

11.
Med Dosim ; 47(3): 222-226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35428548

RESUMO

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. Each patient had a treatment-approved, equivalent IMRT plan to serve as a reference. The main end point was dose delivered to the tubarial salivary glands by modality, assessed via a 2-tailed, paired t-test. We also report disease outcomes for the entire cohort, via the Kaplan-Meier method. Sixty-four patients were identified. The mean RT dose to the tubarial salivary glands was 23.6 Gy (95% confidence interval (CI) 21.7 to 25.5) and 30.4 Gy (28.6 to 32.2) for PRT and IMRT plans (p < 0.0001), respectively. With a median follow-up of 25.2 months, the two-year locoregional control, progression-free survival and overall survival were 97.8% (95% CI 85.6% to 99.7%), 94.1% (82.8% to 98.1%) and 98.1% (87.4% to 99.7%), respectively. Our study suggests that meaningful normal tissue sparing of the recently identified tubarial salivary glands is achievable with PRT. The apparent gains with PRT did not impact disease outcomes, with only 1 observed locoregional recurrence (0 local, 1 regional). Further studies are warranted to explore the impact of the improved dosimetric sparing of the tubarial salivary glands conveyed by PRT on patient toxicity and quality of life.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Glândulas Salivares , Xerostomia , Estudos de Coortes , Humanos , Qualidade de Vida , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Glândulas Salivares/patologia , Glândulas Salivares/efeitos da radiação , Xerostomia/etiologia , Xerostomia/prevenção & controle
12.
Int J Part Ther ; 8(4): 47-54, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530184

RESUMO

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. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results: Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion: Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.

13.
Pract Radiat Oncol ; 12(4): e282-e285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35304348

RESUMO

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. We included patients treated to postoperative doses and standard volumes (including bilateral neck). Doses delivered to organs at risk were compared with recommended dose constraints from a recent cooperative group head and neck cancer trial of radiation therapy to 60 Gy. We applied validated and published NTCP models for dysphagia, dysgeusia, esophagitis, oral mucositis, and xerostomia relevant to oropharyngeal cancer. RESULTS: Achievable and delivered mean doses to most normal head and neck tissues were well below national recommended constraints. This translates to notable absolute NTCP reductions for salivary flow (10% improvement in contralateral parotid, 35% improvement in submandibular gland), grade ≥ 2 esophagitis (23% improvement), grade ≥ 3 mucositis (17% improvement), dysgeusia (10% improvement), and dysphagia (8% improvement). Locoregional control at a median follow-up of 26.3 months was 96.7%, with only 3 patients experiencing locoregional recurrence (1 local, 2 regional). CONCLUSIONS: Modern radiation therapy planning techniques allow for improved normal tissue sparing compared with currently established dose constraints without compromising disease control. These improvements may lead to reduced toxicity in a patient population expected to have favorable long-term outcomes. Stricter constraints can be easily achieved and should be used in conjunction with other evolving efforts to mitigate toxicity.


Assuntos
Transtornos de Deglutição , Esofagite , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Radioterapia de Intensidade Modulada , Transtornos de Deglutição/etiologia , Disgeusia/complicações , Esofagite/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Neoplasias Orofaríngeas/radioterapia , Glândula Parótida , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos
14.
Int J Part Ther ; 8(1): 62-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285936

RESUMO

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. Reference SPRs of tissue-equivalent plugs from Gammex (Middleton, Wisconsin) and CIRS (Computerized Imaging Reference Systems, Norfolk, Virginia) electron density phantoms were used for validation and comparison of SECT versus DECT calculated through the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California) application programming interface scripting tool. An in-house software was also used to create DECT SPR computed tomography images for comparison with the script output. In the workflow, using the Eclipse system application programming interface script, clinical plans were optimized with the SECT image set and then forward-calculated with the DECT SPR for the final dose distribution. In a second workflow, the plans were optimized using DECT SPR with reduced range-uncertainty margins. RESULTS: For the Gammex phantom, the root mean square error in SPR was 1.08% for DECT versus 2.29% for SECT for 10 tissue-surrogates, excluding the lung. For the CIRS Phantom, the corresponding results were 0.74% and 2.27%. When evaluating the head and neck plan, DECT optimization with 2% range-uncertainty margins achieved a small reduction in organ-at-risk doses compared with that of SECT plans with 3.5% range-uncertainty margins. For the liver case, DECT was used to identify and correct the lipiodol SPR in the SECT plan. CONCLUSION: It is feasible to use DECT for proton-dose calculation in a commercial treatment planning system in a safe manner. The range margins can be reduced to 2% in some sites, including the head and neck.

15.
Biomed Phys Eng Express ; 6(6)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-35102004

RESUMO

Purpose: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. The novelty of this study is the first demonstration of the feasibility of pERDI technique in the pencil beam scanning (PBS) mode.Methods:A solid water wedge was placed in front of a 2D detector (Lynx). A library of energy-resolved dose functions (ERDF) was generated from the dose deposited in the detector by 50 PBS layers of energy varying from 100 MeV to 225 MeV. This set-up is further used to image the following configurations using the pERDI technique: stair-case shaped solid water phantom (configuration 1), electron density phantom (configuration 2) and head phantom (configuration 3). The result from configuration 1 was used to determine the achievable WEPL accuracy. The result from configuration 2 was used to estimate the relative uncertainty in RSP. Configuration 3 was used to evaluate the effect of range mixing on the WEPL. In all three cases, the variation of the accuracy with respect to dose, by varying the number of scanning layers, was also studied.Results:An accuracy of 1 mm in WEPL was achieved using the Lynx detector with an imaging field of 10 PBS layers or more, which is equivalent to a total dose of 5 cGy. The RSP is measured with a precision better than 2% for all homogeneous inserts of tissue surrogates. The pERDI technique failed for tissues surrogates with total WEPL outside the calibration window (WEPL < 70 mm) like in the case of lung exhale and lung inhale. The imaging of an anthropomorphic head phantom, in the same condition, produced a WEPL radiograph and compared to the WEPL derived from CT using gamma index analysis. The gamma index failed in the heterogeneous areas due to range mixing.Conclusions:The pERDI technique is a promising clinically usable imaging modality for reducing range uncertainties and set-up errors in proton therapy. The first results have demonstrated that WEPL and RSP can be estimated with clinically acceptable accuracy using the Lynx detector. Similar accuracy is also expected with in-room flat-panel detectors but at significantly reduced imaging dose. Though the issue of range mixing is still to be addressed, we expect that a statistical moment analysis of the ERDFs can be implemented to filter out the regions with high gradient of range mixing.


Assuntos
Terapia com Prótons , Calibragem , Estudos de Viabilidade , Imagens de Fantasmas , Prótons
16.
Adv Radiat Oncol ; 5(5): 943-950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083657

RESUMO

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. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and Dmean. These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values. RESULTS: The multivariate analysis showed V40Gy and Dmean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%. CONCLUSIONS: In addition to V20Gy and Dmean, the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy.

17.
Int J Radiat Oncol Biol Phys ; 107(1): 79-87, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987966

RESUMO

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. The inhale and exhale simulation computed tomography scans were deformed using Advanced Normalization Tools. The 3-dimensional lung ventilation maps were derived from the deformation matrix and partitioned into low- and high-ventilation zones for dosimetric analysis. Receiver operating curve analysis was used to study the power of relationship between RP and ventilation zones to determine an optimal ventilation cutoff. Univariate logistic regression was used to correlate dose in high- and low-ventilation zones with risk of RP. A nonparametric random forest process was used for multivariate importance assessment. RESULTS: The optimal high-ventilation zone definition was determined to be the higher 45% to 60% of the ventilation values. The parameter vV20Gy_high (high ventilation volume receiving ≥20 Gy) was found to be a significant indicator for RP (PH: P = .002, PR: P = .035) with improved areas under the curve compared with the traditional V20Gy for both photon and proton cohorts. The relationship of RP with dose to the low-ventilation zone of the lung was insignificant (PH: P = .123, PR: P = .661). Similar trends were observed for ventilation mean lung dose and ventilation V5Gy. Multivariate importance assessment determined that vV20Gy_high, vV5_high, and mean lung dose were the most significant parameters for the proton cohort with a combined area under the curve of 0.78. CONCLUSION: Dose to the high-ventilated regions of the lung can improve predictions of RP for both PH and PR.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Terapia com Prótons/efeitos adversos , Ventilação Pulmonar/efeitos da radiação , Pneumonite por Radiação/etiologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Masculino , Radiometria
18.
Br J Radiol ; 93(1107): 20190638, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31845816

RESUMO

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 3.5% range uncertainty. Weekly online cone beam CT (CBCT) were performed. Planning CT was deformed to the CBCT to create virtual CTs (vCTs) on which the planned dose was recalculated. vCT plan robustness was evaluated using a setup uncertainty of 1.5 mm and range uncertainty of 3.5%. Target coverage, D95%, and hotspots, D0.03cc, were evaluated for each uncertainty along with the vCT-calculated nominal plan. Mean dose to organs at risk (OARs) for the vCT-calculated nominal plan and relative % change in weight from baseline were evaluated. RESULTS: Robustly optimised plans in post-operative OPC and OCC patients are robust against inter-fraction setup variations and range uncertainty. D0.03cc in the vCT-calculated nominal plans were clinically acceptable across all plans. Across all patients D95% in the vCT-calculated nominal treatment plan was at least 100% of the prescribed dose. No patients lost ≥10% weight from baseline. Mean dose to the OARs and max dose to the spinal cord remained within tolerance. CONCLUSION: MFO plans in post-operative OPC and OCC patients are robust to inter-fraction uncertainties in setup and range when evaluated over multiple CT scans without compromising OAR mean dose. ADVANCES IN KNOWLEDGE: This is the first paper to evaluate inter-fraction MFO plan robustness in post-operative head and neck treatment.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/radioterapia , Neoplasias Orofaríngeas/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Neoplasias Orofaríngeas/diagnóstico por imagem , Projetos Piloto , Cuidados Pós-Operatórios , Estudos Retrospectivos , Medula Espinal/efeitos da radiação , Incerteza
19.
Front Oncol ; 9: 496, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249808

RESUMO

Purpose: 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. The performance of the MV-CBCT in the clinic, including resulting dose to organs, is also discussed herein. Methods: A Gammex phantom was scanned using a Halcyon MV-CBCT and a 120 kVp Siemens Definition Edge CT. Mean and standard deviation of Hounsfield Units (HUs) for different electron density relative to water ( ρ e W ) inserts were extracted. Doses to clinical patients due to MV-CBCT are calculated within Eclipse during treatment planning. Results: A stable and near-linear HU-to- ρ e W curve was obtained using the MV-CBCT. As the scan length increased from 10 to 28cm, the linearity of curve improved while the mean HUs decreased by 30%. All soft tissue inserts in the Gammex phantom were distinguishable. A crescent artifact affected HU measurements by up to 40 HUs. Soft-tissue contrast was sufficient for clinical online image-guidance in the low dose (5 MU) mode. Mean doses per fraction to organs-at-risk (OARs) were as high as 6 cGy for head and neck, 5 cGy for breast, and 4 cGy for pelvis patients. Metal rods did not affect HU values or introduce noticeable artifacts. Conclusions: Halcyon's MV-CBCT has sufficient soft tissue contrast for IGRT and lacks metal-induced artifacts. Even though the absolute HU values vary with phantom size and scanning length, the HU-to- ρ e W conversions are linear and stable day-to-day. In clinical cases, highest tissue doses from MV-CBCT ranged from 2-7cGy per fraction for various treatment sites, which could be significant for some organs at risk. Dose to out-of-treatment-field organs can be limited by reducing the scan length definition during planning and using the low dose mode. The high quality imaging mode did not provide material advantages over the low dose mode. Adequate IGRT was successfully delivered to multiple tumor sites using MV-CBCT.

20.
Front Oncol ; 9: 7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723702

RESUMO

Purpose: To evaluate the dosimetric performance and planning/delivery efficiency of a dual-layer MLC system for treating multiple brain metastases with a single isocenter. Materials and Methods: 10 patients each with 6-10 targets with volumes from 0.11 to 8.57 cc, and prescription doses from 15 to 24 Gy, were retrospectively studied. Halcyon has only coplanar delivery mode. Halcyon V1 MLC modulates only with the lower layer at 1 cm resolution, whereas V2 MLC modulates with both layers at an effective resolution of 0.5 cm. For each patient five plans were compared varying MLC and beam arrangements: the clinical plan using multi-aperture dynamic conformal arc (DCA) and non-coplanar arcs, Halcyon-V1 using coplanar-VMAT, Halcyon-V2 using coplanar-VMAT, HDMLC-0.25 cm using coplanar-VMAT, and HDMLC-0.25 cm using non-coplanar-VMAT. All same-case plans were generated following the same planning protocol and normalization. Conformity index (CI), gradient index (GI), V12Gy, V6Gy, V3Gy, and brain mean dose were compared. Results: All VMAT plans met clinical constraints for critical structures. For targets with diameter < 1 cm, Halcyon plans showed inferior CI among all techniques. For targets with diameter >1 cm, Halcyon VMAT plans had CI similar to non-coplanar VMAT plans, and better than non-coplanar clinical DCA plans. For GI, Halcyon MLC plans performed similarly to coplanar HDMLC plans and inferiorly compared to non-coplanar HDMLC plans. All coplanar VMAT plans (Halcyon MLC and HDMLC) and clinical DCA plans had similar V12Gy, but were inferior compared to non-coplanar VMAT plans. Halcyon plans had slightly reduced V3Gy and mean brain dose compared to HDMLC plans. The difference between Halcyon V1 and V2 is only significant in CI of tumors less than 1cm in diameter. Halcyon plans required longer optimization than Truebeam VMAT plans, but had similar delivery efficiency. Conclusion: For targets with diameter >1 cm, Halcyon's dual-layer stacked and staggered MLC is capable of producing similar dose conformity compared to HDMLC while reducing low dose spill to normal brain tissue. GI and V12Gy of Halcyon MLC plans were, in general, inferior to non-coplanar DCA or VMAT plans using HDMLC, likely due to coplanar geometry and wider MLC leaves. HDMLC maintained its advantage in CI for smaller targets with diameter <1 cm.

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