Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 175
Filtrar
1.
J Natl Compr Canc Netw ; 19(3): 254-266, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33668021

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

2.
Phys Med Biol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657537

RESUMO

Purpose:Radiation dose delivered to targets located near the upper-abdomen or in the thorax are significantly affected by respiratory-motion. Relatively large-margins are commonly added to compensate for this motion, limiting radiation-dose-escalation. Internal-surrogates of target motion, such as a radiofrequency (RF) tracking system, i.e. Calypso® System, are used to overcome this challenge and improve normal-tissue sparing. RF tracking systems consist of implanting transponders in the vicinity of the tumor to be tracked using radiofrequency-waves. Unfortunately, although the manufacture provides a universal quality-assurance (QA) phantom, QA-phantoms specifically for lung-applications are limited, warranting the development of alternative solutions to fulfil the tests mandated by AAPM's TG142. Accordingly, our objective was to design and develop a motion-phantom to evaluate Calypso for lung-applications that allows the Calypso® Beacons to move in different directions to better simulate true lung-motion.Methods and Materials:A Calypso lung QA-phantom was designed, and 3D-printed. The design consists of three independent arms where the transponders were attached. A pinpoint-chamber with a buildup-cap was also incorporated. A 4-axis robotic arm was programmed to drive the motion-phantom to mimic breathing. After acquiring a four-dimensional-computed-tomography (4DCT) scan of the motion-phantom, treatment-plans were generated and delivered on a Varian TrueBeam® with Calypso capabilities. Stationary and gated-treatment plans were generated and delivered to determine the dosimetric difference between gated and non-gated treatments. Portal cine-images were acquired to determine the temporal-accuracy of delivery by calculating the difference between the observed versus expected transponders locations with the known speed of the transponders' motion.Results:Dosimetric accuracy is better than TG142 tolerance of 2%. Temporal accuracy is greater than, TG142 tolerance of 100ms for beam-on, but less than 100ms for beam-hold.Conclusions:The robotic QA-phantom designed and developed in this study provides an independent phantom for performing Calypso lung-QA for commissioning and acceptance testing of Calypso for lung treatments.

3.
Phys Med Biol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657538

RESUMO

PURPOSE: To develop an automated optimization strategy to facilitate collimator design for small-field radiotherapy systems. METHODS: We developed an objective function that links the dose profile characteristics (FWHM, penumbra, and central dose rate) and the treatment head geometric parameters (collimator thickness/radii, source-to-distal-collimator distance[SDC]) for small-field radiotherapy systems. We performed optimization using a downhill simplex algorithm. We applied this optimization strategy to a linac-based radiosurgery system to determine the optimal geometry of four pencil-beam collimators to produce 5, 10, 15, and 20mm diameter photon beams (from a 6.7MeV, 2.1mmFWHM electron beam). Two different optimizations were performed to prioritize minimum penumbra or maximum central dose rate for each beam size. We compared the optimized geometric parameters and dose distributions to an existing clinical system (CyberKnife). RESULTS: When minimum penumbra was prioritized, using the same collimator thickness and SDC (40cm) as a CyberKnife system, the optimized collimator upstream and downstream radii agreed with the CyberKnife system within 3-14%, the optimized output factors agreed within 0-8%, and the optimized transverse and percentage depth dose profiles matched those of the CyberKnife with the penumbras agreeing within 2%. However, when maximum dose rate was prioritized, allowing both the collimator thickness and SDC to change, the central dose rate for larger collimator sizes (10, 15, 20mm) could be increased by about 1.5-2 times at the cost of 1.5-2 times larger penumbras. No further improvement in central dose rate for the 5mm beam size could be achieved. CONCLUSIONS: We developed an automated optimization strategy to design the collimator geometry for small-field radiation therapy systems. Using this strategy, the penumbra-prioritized dose distribution and geometric parameters agree well with the CyberKnife system as an example, suggesting that this system was designed to prioritize sharp penumbra. This represents proof-of-principle that an automated optimization strategy may apply to more complex collimator designs with multiple optimization parameters.

4.
J Thorac Oncol ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33588109

RESUMO

INTRODUCTION: In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown. METHODS: We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab. RESULTS: Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib. CONCLUSIONS: In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33545301

RESUMO

PURPOSE: The differential response of normal and tumor tissues to ultrahigh-dose-rate radiation (FLASH) has raised new hope for treating solid tumors but, to date, the mechanism remains elusive. One leading hypothesis is that FLASH radiochemically depletes oxygen from irradiated tissues faster than it is replenished through diffusion. The purpose of this study was to investigate these effects within hypoxic multicellular tumor spheroids through simulations and experiments. METHODS AND MATERIALS: Physicobiological equations were derived to model (1) the diffusion and metabolism of oxygen within spheroids; (2) its depletion through reactions involving radiation-induced radicals; and (3) the increase in radioresistance of spheroids, modeled according to the classical oxygen enhancement ratio and linear-quadratic response. These predictions were then tested experimentally in A549 spheroids exposed to electron irradiation at conventional (0.075 Gy/s) or FLASH (90 Gy/s) dose rates. Clonogenic survival, cell viability, and spheroid growth were scored postradiation. Clonogenic survival of 2 other cell lines was also investigated. RESULTS: The existence of a hypoxic core in unirradiated tumor spheroids is predicted by simulations and visualized by fluorescence microscopy. Upon FLASH irradiation, this hypoxic core transiently expands, engulfing a large number of well-oxygenated cells. In contrast, oxygen is steadily replenished during slower conventional irradiation. Experimentally, clonogenic survival was around 3-fold higher in FLASH-irradiated spheroids compared with conventional irradiation, but no significant difference was observed for well-oxygenated 2-dimensional cultured cells. This differential survival is consistent with the predictions of the computational model. FLASH irradiation of spheroids resulted in a dose-modifying factor of around 1.3 for doses above 10 Gy. CONCLUSIONS: Tumor spheroids can be used as a model to study FLASH irradiation in vitro. The improved survival of tumor spheroids receiving FLASH radiation confirms that ultrafast radiochemical oxygen depletion and its slow replenishment are critical components of the FLASH effect.

6.
Sci Rep ; 10(1): 21600, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303827

RESUMO

Radiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33186615

RESUMO

PURPOSE: To investigate whether the vascular collapse in tumors by conventional dose rate (CONV) irradiation (IR) would also occur by the ultra-high dose rate FLASH IR. METHODS AND MATERIALS: Lewis lung carcinoma (LLC) were subcutaneously implanted in mice followed by CONV or FLASH IR at 15 Gy. Tumors were harvested at 6 or 48 hr post-IR and stained for CD31, phosphorylated myosin-light chain (p-MLC), γH2AX, intracellular reactive oxygen species (ROS), or immune cells such as myeloid and CD8α T cells. Cell lines were irradiated with CONV IR for Western blot analyses. ML-7 was intraperitoneally administered daily to LLC-bearing mice for 7 days prior to 15 Gy CONV IR. Tumors were similarly harvested and analyzed as above. RESULTS: By immunostaining, we observed that CONV IR at 6 hr post-IR resulted in constricted vessel morphology, increased expression of phosphorylated myosin light chain (p-MLC), and much higher numbers of γH2AX (surrogate marker for DNA double strand break)-positive cells in tumors, which were not observed with FLASH IR. Mechanistically, we found that MLC activation by reactive oxygen species (ROS) is unlikely since FLASH IR produced significantly higher ROS than CONV IR in tumors. In vitro studies demonstrated that ML-7, an inhibitor of MLC kinase abrogated IR-induced γH2AX formation and disappearance kinetics. Lastly, we observed that CONV IR when combined with ML-7 produced some effects similar to FLASH IR including the reduction in the vasculature collapse, fewer γH2AX-positive cells, and increased immune cell influx to the tumors. CONCLUSIONS: FLASH IR produced novel changes in the tumor microenvironment that were not observed with CONV IR. We believe that MLC activation in tumors may be responsible for some of those microenvironmental changes differentially regulated between CONV and FLASH IR.

8.
Cancer Discov ; 10(12): 1826-1841, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33071215

RESUMO

Tumor genotyping is not routinely performed in localized non-small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in tumors with KEAP1/NFE2L2 mutations, indicating that they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1-mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations. SIGNIFICANCE: This study shows that mutations in KEAP1 and NFE2L2 predict for LR after radiotherapy but not surgery in patients with NSCLC. Approximately half of all LRs are associated with these mutations and glutaminase inhibition may allow personalized radiosensitization of KEAP1/NFE2L2-mutant tumors.This article is highlighted in the In This Issue feature, p. 1775.

9.
Radiat Res ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991725

RESUMO

In this work, we investigated the delivery of a clinically acceptable pediatric whole brain radiotherapy plan at FLASH dose rates using two lateral opposing 40-MeV electron beams produced by a practically realizable linear accelerator system. The EGSnrc Monte Carlo software modules, BEAMnrc and DOSXYZnrc, were used to generate whole brain radiotherapy plans for a pediatric patient using two lateral opposing 40-MeV electron beams. Electron beam phase space files were simulated using a model of a diverging beam with a diameter of 10 cm at 50 cm SAD (defined at brain midline). The electron beams were collimated using a 10-cm-thick block composed of 5 cm of aluminum oxide and 5 cm of tungsten. For comparison, a 6-MV photon plan was calculated with the Varian AAA algorithm. Electron beam parameters were based on a novel linear accelerator designed for the PHASER system and powered by a commercial 6-MW klystron. Calculations of the linear accelerator's performance indicated an average beam current of at least 6.25 µA, providing a dose rate of 115 Gy/s at isocenter, high enough for cognition-sparing FLASH effects. The electron plan was less homogenous with a homogeneity index of 0.133 compared to the photon plan's index of 0.087. Overall, the dosimetric characteristics of the 40-MeV electron plan were suitable for treatment. In conclusion, Monte Carlo simulations performed in this work indicate that two lateral opposing 40-MeV electron beams can be used for pediatric whole brain irradiation at FLASH dose rates of 115 Gy/s and serve as motivation for a practical clinical FLASH radiotherapy system, which can be implemented in the near future.

10.
J Thorac Cardiovasc Surg ; 160(5): 1331-1345.e1, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32798022

RESUMO

OBJECTIVE: Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non-small cell lung cancer. METHODS: Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non-small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here. RESULTS: One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9). CONCLUSIONS: Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pneumonectomia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos
11.
Radiat Res ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853385

RESUMO

Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival >180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.

12.
Radiat Res ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32857849

RESUMO

The observation of an enhanced therapeutic index for FLASH radiotherapy in mice has created interest in practical laboratory-based FLASH irradiators. To date, systems capable of 3D conformal FLASH irradiation in mice have been lacking. We are developing such a system, incorporating a high-current linear accelerator to produce a collimated X-ray beam in a stationary beamline design, rotating the mouse about a longitudinal axis to achieve conformal irradiation from multiple beam directions. The purpose of this work was to evaluate the reproducibility of mouse anatomy under rotation at speeds compatible with conformal FLASH delivery. Three short-hair mice and two hairless mice were immobilized under anesthesia in body weight-specific contoured plastic molds, and subjected to three rotational (up to 3 revolutions/s) and two non-rotational movement interventions. MicroCT images were acquired before and after each intervention. The displacements of 11 anatomic landmarks were measured on the image pairs. The displacement of the anatomical landmarks with any of the interventions was 0.5 mm or less for 92.4% of measurements, with a single measurement out of 275 (11 landmarks × 5 interventions × 5 mice) reaching 1 mm. There was no significant difference in the displacements associated with rotation compared to those associated with moving the immobilized mouse in and out of a scanner or with leaving the mouse in place for 5 min with no motion. There were no significant differences in displacements between mice with or without hair, although the analysis is limited by small numbers, or between different anatomic landmarks. These results show that anatomic reproducibility under rotation speed corresponding to FLASH irradiation times appears to be compatible with conformal/stereotactic irradiation in mice.

13.
Semin Radiat Oncol ; 30(2): 194-200, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32381299

RESUMO

Radiation therapy benefits the majority of patients across the spectrum of cancer types. However, both local and distant tumor recurrences limit its clinical success. While departing from the established tenet of fractionation in clinical radiotherapy, ablative-intensity hypofractionated radiotherapy, especially stereotactic radiosurgery and stereotactic ablative radiotherapy, has emerged as an alternative paradigm achieving unprecedented rates of local tumor control. Direct tumor cell killing has been assumed to be the primary therapeutic mode of action of such ablative radiation. But with increasing recognition that tumor responses also depend on the immunostimulatory or immunosuppressive status of the tumor microenvironment, the immunologic effect of ablative radiotherapy is emerging as a key contributor to antitumor response. More recently, novel radiation modalities, such as spatially fractionated radiotherapy and ultrahigh dose rate FLASH irradiation, that venture even further from conventional paradigms have shown promise of increasing the therapeutic index of radiation therapy with the potential of immunomodulation. Here, we review the immunomodulatory impact of novel radiation therapy paradigms, heretofore considered radiobiological heresies, a deeper understanding of which is imperative to realizing fully their potential for more curative cancer therapy.

14.
Radiat Oncol ; 15(1): 114, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429982

RESUMO

BACKGROUND: We evaluated whether pre- and mid-treatment metabolic tumor volume (MTV) predicts per lesion local recurrence (LR) in patients treated with definitive radiation therapy (RT, dose≥60 Gy) for locally advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed records of patients with stage III NSCLC treated from 2006 to 2018 with pre- and mid-RT PET-CT. We measured the MTV of treated lesions on the pre-RT (MTVpre) and mid-RT (MTVmid) PET-CT. LR was defined per lesion as recurrence within the planning target volume. Receiver operating characteristic (ROC) curves, cumulative incidence rates, and uni- and multivariable (MVA) competing risk regressions were used to evaluate the association between MTV and LR. RESULTS: We identified 111 patients with 387 lesions (112 lung tumors and 275 lymph nodes). Median age was 68 years, 69.4% were male, 46.8% had adenocarcinoma, 39.6% had squamous cell carcinoma, and 95.5% received concurrent chemotherapy. Median follow-up was 38.7 months. 3-year overall survival was 42.3%. 3-year cumulative incidence of LR was 26.8% per patient and 11.9% per lesion. Both MTVpre and MTVmid were predictive of LR by ROC (AUC = 0.71 and 0.76, respectively) and were significantly associated with LR on MVA (P = 0.004 and P = 7.1e-5, respectively). Among lesions at lower risk of LR based on MTVpre, higher MTVmid was associated with LR (P = 0.001). CONCLUSION: Per-lesion, larger MTVpre and MTVmid predicted for increased risk of LR. MTVmid was more highly predictive of LR than MTVpre and if validated may allow for further discrimination of high-risk lesions at mid-RT informing dose painting strategies.

15.
Int J Radiat Oncol Biol Phys ; 107(4): 766-778, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32298811

RESUMO

The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.

16.
Nature ; 580(7802): 245-251, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32269342

RESUMO

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.


Assuntos
DNA Tumoral Circulante/análise , DNA Tumoral Circulante/genética , Detecção Precoce de Câncer/métodos , Genoma Humano/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação , Estudos de Coortes , Feminino , Hematopoese/genética , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
17.
J Appl Clin Med Phys ; 21(3): 162-166, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32107845

RESUMO

PURPOSE: As C-arm linac radiation therapy evolves toward faster, more efficient delivery, and more conformal dosimetry, treatments with increasingly complex couch motions are emerging. Monitoring the patient motion independently of the couch motion during non-coplanar, non-isocentric, or dynamic couch treatments is a key bottleneck to their clinical implementation. The goal of this study is to develop a prototype real-time monitoring system for unconventional beam trajectories to ensure a safe and accurate treatment delivery. METHODS: An in-house algorithm was developed for tracking using a couch-mounted three-dimensional (3D) depth camera. The accuracy of patient motion detection on the couch was tested on a 3D printed phantom created from the body surface contour exported from the treatment planning system. The technique was evaluated against a commercial optical surface monitoring system with known phantom displacements of 3, 5, and 7 mm in lateral, longitudinal, and vertical directions by placing a head phantom on a dynamic platform on the treatment couch. The stability of the monitoring system was evaluated during dynamic couch trajectories, at speeds between 10.6 and 65 cm/min. RESULTS: The proposed monitoring system agreed with the ceiling mounted optical surface monitoring system in longitudinal, lateral, and vertical directions within 0.5 mm. The uncertainty caused by couch vibration increased with couch speed but remained sub-millimeter for speeds up to 32 cm/min. For couch speeds of 10.6, 32.2, and 65 cm/min, the uncertainty ranges were 0.27- 0.73 mm, 0.15-0.87 mm, and 0.28-1.29 mm, respectively. CONCLUSION: By mounting a 3D camera in the same frame-of-reference as the patient and eliminating dead spots, this proof of concept demonstrates real-time patient monitoring during couch motion. For treatments with non-coplanar beams, multiple isocenters, or dynamic couch motion, this provides additional safety without additional radiation dose and avoids some of the complexity and limitations of room mounted systems.

18.
Pract Radiat Oncol ; 10(4): e272-e279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935524

RESUMO

PURPOSE: Pediatric radiation therapy (RT) requires optimal immobilization that often necessitates daily anesthesia. To decrease anesthesia use, we implemented a novel audiovisual-assisted therapeutic ambience in RT (AVATAR) system that projects video onto a radiolucent screen within the child's line of vision to provide attentional diversion. We investigated its reduction on anesthesia use, payer charges, and treatment time, in addition to its impact on radiation delivery. METHODS AND MATERIALS: A 6-year retrospective analysis was performed among children undergoing RT (n = 224) 3 years before and 3 years after the introduction of AVATAR. The frequency of anesthesia use before and after AVATAR implementation, in addition to RT treatment times, were compared. The number of spared anesthesia treatments allowed for a charge to payer analysis. To document the lack of surface dose perturbation by AVATAR, a phantom craniospinal treatment course was delivered both with and without AVATAR. Additionally, an ion chamber course was delivered to document changes to the dose at depth. RESULTS: More children were able to avoid anesthesia use entirely in the post-AVATAR cohort compared with the pre-AVATAR cohort (73.2% vs 63.4%; P = .03), and fewer required anesthesia for each treatment (18.8% vs 33%; P = .03). AVATAR introduction reduced anesthesia use for all ages studied. Treatment time per session was reduced by 38% using AVATAR compared with anesthesia. There were 326 fewer anesthesia sessions delivered over 3 years after AVATAR was introduced, with an estimated savings of >$500,000. Optically stimulated luminescent dosimeters revealed a small increase in dose of 0.8% to 9.5% with AVATAR, whereas the use of a thermomolded face mask increased skin dose by as much as 58%. CONCLUSIONS: AVATAR introduction decreased anesthesia use in children undergoing RT. More children avoided anesthesia entirely, and fewer needed anesthesia for every treatment, resulting in a reduction in treatment time and savings of nearly $550,000 in approximately 3 years, with minimal perturbation of RT dose delivery.

19.
Pract Radiat Oncol ; 10(2): e91-e94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31574319

RESUMO

PURPOSE: Because children cannot reliably remain immobile during radiation therapy (RT) for cancer anatomy targeting requiring millimeter precision, daily anesthesia plays a large role in each RT session. Unfortunately, anesthesia is a source of financial burden for patients' families and is invasive and traumatic. This study attempts to assess the cost-savings benefit of audiovisual-assisted therapeutic ambiance in radiation therapy (AVATAR)-aided omission of pediatric anesthesia in RT. METHODS AND MATERIALS: The baseline time of anesthesia during RT was derived from documented anesthesia billing time during RT simulation at our institution and from the published literature. Current Procedural Terminology and relative value unit codes encompassing anesthesia-related charges from radiation oncology and anesthesia were analyzed in concert with this value to calculate the total cost of pediatric anesthesia per RT session. RESULTS: The mean number of RT fractions administered per patient with AVATAR-directed anesthesia omission at our institution was 19.0, similar to the 17.6 previously reported. At a mean anesthesia time exceeding 30 minutes (with mean RT duration of 4 weeks), the cost of pediatric anesthesia per RT fraction in non-AVATAR sessions was $1,904.35, yielding a total RT treatment anesthesia cost of $38,087.00 per patient (including simulation). Patients at our institution were not billed for AVATAR-assisted RT. CONCLUSIONS: The ability of AVATAR to obviate the need for daily anesthesia in pediatric RT provides substantial cost-savings. These findings argue for increased utilization of AVATAR and for analyses of RT targeting the accuracy of AVATAR versus conventional anesthesia-guided treatment of pediatric malignancies.


Assuntos
Recursos Audiovisuais/normas , Custos de Cuidados de Saúde/normas , Neoplasias/economia , Neoplasias/radioterapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
20.
J Natl Compr Canc Netw ; 17(12): 1464-1472, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805526

RESUMO

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...