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1.
Radiat Oncol ; 17(1): 4, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991637

RESUMO

BACKGROUND: Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy). METHODS: The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/ß of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer. RESULTS: Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2-3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting. CONCLUSIONS: This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.

3.
Chronobiol Int ; : 1-13, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34983277

RESUMO

The hippocampus, an extension of the temporal part of the cerebral cortex, plays a crucial role in learning and memory. Structural and functional complexity within the hippocampus is greatly affected by a variety of external environmental stimuli including alteration in the light-dark (LD) cycle. The effect of altered LD cycle in learning and memory associated cognitive impairment has been reported in rodents. However, a comparative study of underlying neuronal changes between nocturnal and diurnal species is not well explored. The objective of the present study was to explore the morphological changes in hippocampal CA1 and DG neurons in response to prolonged constant condition viz. constant light (LL) and constant darkness (DD) in diurnal squirrels and nocturnal mice. Animals (n = 5/group) were placed in chronocubicle under 12:12 h LD, LL and DD. After four weeks, brain tissues were collected and processed for Golgi-Cox staining to analyze morphological changes in CA1 and DG neurons. The total and basal dendritic length, basal dendrite number, branch end, the diameter of apical dendrite and spine density were analyzed. The results showed a significant reduction in structural complexity of CA1 and DG neurons of squirrels exposed to prolonged constant darkness, whereas mice showed a significant increase as compared to LD. However, a significantly reduced neuronal complexity was observed in both squirrels and mice exposed to prolonged constant light. The results obtained were further confirmed by Sholl analysis of CA1 and DG neurons. The present study suggests that prolonged constant light may cause adverse effects on the neuronal complexity of both diurnal and nocturnal animals, but constant darkness may cause adverse effects mainly to the diurnal animals.

4.
J Colloid Interface Sci ; 607(Pt 2): 978-991, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34571316

RESUMO

Lipid cubic phase (LCP) formulations enhance the intestinal solubility and bioavailability of hydrophobic drugs by reducing precipitation and facilitating their mass transport to the intestinal surface for absorption. LCPs with an ester linkage connecting the acyl chain to the glycerol backbone (monoacylglycerols), are susceptible to chemical digestion by several lipolytic enzymes including lipases, accelerating the release of hydrophobic agents from the lipid bilayers of the matrix. Unlike regular enzymes that transform soluble substrates, lipolytic enzymes act at the interface of water and insoluble lipid. Therefore, compounds that bind to this interface can enhance or inhibit the activity of enzymes to varying extent. Here, we explore how the lipolysis rate can be tuned by the interfacial interaction of porcine pancreatic lipase with monoolein LCPs containing a known lipase inhibitor, tetrahydrolipstatin. Release of the Biopharmaceutical Classification System (BCS) class IV drug, paclitaxel, from the inhibitor-modified LCP was examined in the presence of lipase and its effectors colipase and calcium. By combining experimental dynamic digestion studies, thermodynamic measurements and molecular dynamics simulations of the competitive inhibition of lipase by tetrahydrolipstatin, we reveal the role and mode of action of lipase effectors in creating a precisely-balanced degradation-controlled LCP release system for the poorly soluble paclitaxel drug.


Assuntos
Lipase , Paclitaxel , Animais , Interações Hidrofóbicas e Hidrofílicas , Lipase/metabolismo , Lipídeos , Lipólise , Pâncreas/metabolismo , Suínos
5.
Front Oncol ; 11: 754838, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868962

RESUMO

Purpose: This retrospective observational study examined patients who experienced radiotherapy (RT) interruption during the Wuhan lockdown for the novel coronavirus disease 2019 (COVID-19) pandemic. Materials and Methods: The data of all patients whose RT was interrupted during the Wuhan lockdown from January 23 to April 8, 2020 were collected. Patient-, cancer-, and treatment-related characteristics were analyzed, along with interruption time, disease progression type, and survival status. The methods employed in order to compensate for RT interruption were also described. Results: There were altogether 129 cancer patients whose RT was interrupted. Nineteen (14.7%) patients experienced a total interruption time of at most 7 days; the interruption time was 8-14 days for 27 (20.9%) patients, and 15 or more days for 47 (36.4%) patients. The remaining 36 (27.9%) patients did not come back to our hospital for further RT. We first describe our experience with re-immobilization and/or re-planning (n = 17) as well as dose compensation/adjustment. Of the 40 definitive radiotherapy patients, 37 had squamous cell carcinoma of nasopharyngeal, lung, or cervical origin. Most patients (85/93, 91.4%) were followed up for more than one year. Among the 40 patients who received definitive radiotherapy, nine patients experienced disease progression and five patients died. Three of the seven (42.9%) patients who did not finish radiotherapy after interruption died, as compared to only two of the 33 (6.1%) patients who completed radiotherapy. EQD2 (equivalent dose in 2 Gy fractions) at the time point of RT interruption was calculated. Five of the six patients (83.3%) who received EQD2 ≤10 Gy suffered from disease progression, compared with four of the 34 (11.8%) patients who received EQD2 >10 Gy. For the seven definitive radiotherapy cases who did not finish radiotherapy, three received systemic anti-cancer treatments and three died (all of whom did not receive further systemic therapies). Conclusions: This study provides the longest follow-up for the outcomes of RT interruption during COVID-19 pandemic to date. It cannot imply causation but implies that completing RT is important, along with the utility of having patients remain on systemic therapies if RT is to be interrupted.

7.
Acta Oncol ; : 1-6, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34913815

RESUMO

PURPOSE: It is essential to evaluate the risk of occult lymph node (LN) disease in early-stage non-small cell lung cancer (NSCLC), especially because delivering stereotactic ablative radiotherapy (SABR) assumes no occult spread. This study was designed to assist clinicians in roughly quantifying this risk for cN0 NSCLC. METHODS: The National Cancer Data Base was queried for cN0 cM0 lung squamous cell or adenocarcinoma who underwent surgery and LN dissection without neoadjuvant therapy. Statistics included multivariable logistic regression to evaluate factors associated with pN + disease. RESULTS: 109,964 patients were included. For tumors with size ≤1.0, 1.1-2.0, 2.1-3.0, 3.1-4.0, 4.1-5.0, 5.1-6.0, 6.1-7.0, and >7.0 cm, the pN + rate was 4.4, 7.7, 12.9, 18.0, 20.2, 22.5, 24.4, and 26.4%, respectively. When examining patients with more complete LN dissections (defined as removal of at least 10 LNs), the respective values were 6.6, 11.5, 17.6, 25.3, 26.8, 29.7, 30.7, and 31.6%. Moderately-poorly differentiated disease and adenocarcinomas were associated with a higher rate of pN + disease (p < .001 for both). For every cm increase in tumor size, the relative occult nodal risk increased by 10-14% (p < .001). For every elapsed day from initial diagnosis, the relative risk increased by ∼1% (p < .001). Graphs with best-fit lines were created based on tumor size, histology, and differentiation to aid physicians in estimating the pN + risk. CONCLUSIONS: This nationwide study can allow clinicians to roughly estimate the rate of occult LN disease in cN0 NSCLC. These data can also assist in guiding enrollment on randomized trials of SABR ± immunotherapy, individualizing follow-up imaging surveillance, and patient counseling to avoid post-diagnosis delays.

8.
Pain ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34913882

RESUMO

ABSTRACT: The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.

9.
Front Immunol ; 12: 774807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925345

RESUMO

Radiation-induced lung injury (RILI) is a form of radiation damage to normal lung tissue caused by radiotherapy (RT) for thoracic cancers, which is most commonly comprised of radiation pneumonitis (RP) and radiation pulmonary fibrosis (RPF). Moreover, with the widespread utilization of immunotherapies such as immune checkpoint inhibitors as first- and second-line treatments for various cancers, the incidence of immunotherapy-related lung injury (IRLI), a severe immune-related adverse event (irAE), has rapidly increased. To date, we know relatively little about the underlying mechanisms and signaling pathways of these complications. A better understanding of the signaling pathways may facilitate the prevention of lung injury and exploration of potential therapeutic targets. Therefore, this review provides an overview of the signaling pathways of RILI and IRLI and focuses on their crosstalk in diverse signaling pathways as well as on possible mechanisms of adverse events resulting from combined radiotherapy and immunotherapy. Furthermore, this review proposes potential therapeutic targets and avenues of further research based on signaling pathways. Many new studies on pyroptosis have renewed appreciation for the value and importance of pyroptosis in lung injury. Therefore, the authors posit that pyroptosis may be the common downstream pathway of RILI and IRLI; discussion is also conducted regarding further perspectives on pyroptosis as a crucial signaling pathway in lung injury treatment.

10.
Front Med (Lausanne) ; 8: 723396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616754

RESUMO

Introduction: Lung metastasis is usually associated with poor outcomes in cancer patients. This study was performed to characterize and analyze the population of patients with de novo (synchronous) lung metastases using the Surveillance, Epidemiology and End Results (SEER) database. Materials and Methods: Baseline characteristics of lung metastasis patients were obtained from SEER case listings. Incidence rates and counts of synchronous lung metastasis were also obtained using the SEER*Stat software. Survival outcomes were analyzed using univariate and multivariable Cox regressions, controlling for confounders. An alpha threshold of 0.05 was used for statistical significance and p-values were subject to correction for multiple comparisons. Results: The age-adjusted incidence rate of synchronous lung metastasis was 17.92 per 100,000 between 2010 and 2015. Synchronous lung metastases most commonly arose from primary lung cancers, colorectal cancers, kidney cancers, pancreatic cancers and breast cancers. During this time period, 4% of all cancer cases presented with synchronous lung metastasis. The percentage of patients presenting with synchronous lung metastasis ranged from 0.5% of all prostate cancers to 13% of all primary lung cancers. The percentage of all cancer cases presenting with synchronous lung metastasis increased over time. De novo metastatic patients with lung metastases had worse overall survival [hazard ratio = 1.22 (1.21-1.23), p < 0.001] compared to those with only extrapulmonary metastases, controlling for potential confounders. Conclusions: Synchronous lung metastasis occurs frequently and is an independent predictors of poor patient outcomes. As treatment for lung metastases becomes more complicated, patients with synchronous lung metastasis represent a high-risk population.

11.
Cancer Commun (Lond) ; 41(11): 1086-1099, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34658186

RESUMO

The efficacy of immunotherapy for advanced non-small cell lung cancer (NSCLC) remains unsatisfactory, as the majority of patients either do not experience an objective response or acquire secondary resistance. As a result, several methods to enhance the systemic efficacy of immunotherapy have been investigated, including a large area of active research by combining immunotherapy with radiation therapy (RT). Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit, we review the progress in this field thus far and explore further avenues for enhancing this combination. This review commences with a discussion of the only two existing randomized trials (and a pooled analysis) showing that the addition of RT to immunotherapy improves the abscopal response rate, progression-free survival, and overall survival in metastatic NSCLC patients. We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT, such as low programmed cell death protein ligand 1 (PD-L1) status, tumor mutational burden (TMB), and patient's immune function. Next, the implementation of RT to overcome immunotherapy resistance is discussed, including a mechanistic discussion and methods with which these mechanisms could be exploited. Lastly, the emerging role of low-dose RT is discussed, which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration. Taken together, given the current state of this rapidly expanding realm, these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.

12.
Front Oncol ; 11: 737425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497773

RESUMO

Radiation therapy (RT) is emerging as an interventional modality in the cancer-immunity cycle, augmenting the activation of an adaptive immune response against tumors. RT, particularly in combination with immunotherapy, can enhance immune memory effects and shape the tumor-directed T-cell populations. However, a single cycle of RT delivered to a limited number of polymetastatic lesions is rarely sufficient to achieve systemic control. We hypothesize that several rounds of RT, akin to several rounds of immunotherapeutic drugs, is likely to provide greater clinical benefit to patients with metastatic disease. We propose that the repeated exposure to tumor antigens released by "pulsed-RT" (i.e., treating 2-4 tumor lesions with 3 irradiation cycles given one month apart) may amplify the adaptive immune response by expanding the tumor-specific T-cell receptor repertoire, the production of high-affinity tumor antibodies, and the generation of memory lymphocytes and thereby improve immune control of systemic disease.

13.
Sci Rep ; 11(1): 17801, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493749

RESUMO

Urinary tract infections (UTI) are the most common infectious diseases in the world. It is becoming increasingly tough to treat because of emergence of antibiotic resistance. So, there is an exigency to develop novel anti-virulence therapeutics to combat multi-drug resistance pathogenic strains. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) discovery has revolutionized the gene editing technology for targeted approach. The greatest obstacle for CRISPR/Cas9 is cargo delivery systems and both viral and plasmid methods have disadvantages. Here, we report a highly efficient novel CRISPR based gene editing strategy, CRISPR-dots for targeting virulence factor Fimbrial Adhesion (papG gene), the bacterial adhesion molecule. Carbon quantum dots (CQD) were used as a delivery vehicle for Cas9 and gRNA into CFT073, a UPEC strain. CQDs were covalently conjugated to cas9 and papG-targeted guide RNA (gRNA) forming a nanocomplex CRISPR-dots (Cri-dots) as confirmed by DLS and transmission electron microscopy. Cri-dots-papG significantly targeted papG as demonstrated by decrease in the expression of papG.Further papG deficient UPEC had significantly reduced adherence ability and biofilm forming ability as demonstrated by fluorescence microscopy and scanning electron microscopy. Also, papG deficient UPEC had reduced virulence as shown by significantly increased survival of Caenorhabditis elegans (C. elegans) worms compared to UPEC. Our findings suggest that targeting of papG gene using Cri-dots nanocomplexes significantly reduced the pathogenicity of UPEC. Thus, Cri-dots nanocomplex offer a novel anti-bacterial strategy against multi-drug resistant UPEC.


Assuntos
Adesinas de Escherichia coli/genética , Sistemas CRISPR-Cas , Infecções por Escherichia coli/microbiologia , Proteínas de Fímbrias/genética , Edição de Genes/métodos , Pontos Quânticos/administração & dosagem , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/genética , Animais , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Proteína 9 Associada à CRISPR/administração & dosagem , Proteína 9 Associada à CRISPR/genética , Caenorhabditis elegans/microbiologia , Carbono , Sistemas de Liberação de Medicamentos , Escherichia coli K12/efeitos dos fármacos , Escherichia coli K12/genética , Células HeLa , Hemaglutinação/efeitos dos fármacos , Humanos , Manose/farmacologia , Veículos Farmacêuticos , Pontos Quânticos/toxicidade , RNA Guia/administração & dosagem , RNA Guia/genética , Células THP-1 , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/isolamento & purificação , Escherichia coli Uropatogênica/patogenicidade , Virulência/genética
14.
PLoS One ; 16(9): e0257429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582481

RESUMO

BACKGROUND: The COVID-19 pandemic has brought to light the lacunae in the preparedness of healthcare systems across the globe. This preparedness also includes the safety of healthcare providers (HCPs) at various levels. Sudden spread of COVID-19 infection has created threatening and vulnerable conditions for the HCPs. The current pandemic situation has not only affected physical health of HCPs but also their mental health. OBJECTIVE: This study aims to understand the prevalence and severity of secondary traumatic stress, optimism parameters, along with states of mood experienced by the HCPs, viz., doctors, nurses and allied healthcare professionals (including Physiotherapist, Lab technicians, Phlebotomist, dieticians, administrative staff and clinical pharmacist), during the COVID-19 lockdown in India. METHODOLOGY: The assessment of level of secondary traumatic stress (STS), optimism/pessimism (via Life Orientation Test-Revised) and current mood states experienced by Indian HCPs in the present COVID-19 pandemic situation was done using a primary data of 2,008 HCPs from India during the first lockdown during April-May 2020. Data was collected through snow-ball sampling technique, reaching out to various medical health care professionals through social media platforms. RESULT: Amongst the study sample 88.2% of doctors, 79.2 of nurses and 58.6% of allied HCPs were found to have STS in varying severity. There was a female preponderance in the category of Severe STS. Higher optimism on the LOTR scale was observed among doctors at 39.3% followed by nurses at 26.7% and allied health care professionals 22.8%. The mood visual analogue scale which measures the "mood" during the survey indicated moderate mood states without any gender bias in the study sample. CONCLUSION: The current investigation sheds light on the magnitude of the STSS experienced by the HCPs in the Indian Subcontinent during the pandemic. This hitherto undiagnosed and unaddressed issue, calls for a dire need of creating better and accessible mental health programmes and facilities for the health care providers in India.


Assuntos
Fadiga por Compaixão/psicologia , Pessoal de Saúde/psicologia , Otimismo/psicologia , Ansiedade/epidemiologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Fadiga por Compaixão/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Saúde Mental , Pandemias , Prevalência , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
15.
Med Dosim ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34583857

RESUMO

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.

16.
Plant Cell Rep ; 40(11): 2021-2036, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34591154

RESUMO

KEY MESSAGE: An integrated research approach to ensure sustainable rice yield increase of a crop grown by 25% of the world's farmers in 10% of cropland is essential for global food security. Rice, being a global staple crop, feeds about 56% of the world population and sustains 40% of the world's poor. At ~ $200 billion, it also accounts for 13% of the annual crop value. With hunger and malnutrition rampant among the poor, rice research for development is unique in global food and nutrition security. A systems-based, sustainable increase in rice quantity and quality is imperative for environmental and biodiversity benefits. Upstream 'discovery' through biotechnology, midstream 'development' through breeding and agronomy, downstream 'dissemination and deployment' must be 'demand-driven' for 'distinct socio-economic transformational impacts'. Local agro-ecology and livelihood nexus must drive the research agenda for targeted benefits. This necessitates sustained long-term investments by government, non-government and private sectors to secure the future food, nutrition, environment, prosperity and equity status.

18.
Lancet Oncol ; 22(10): 1448-1457, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34529930

RESUMO

BACKGROUND: A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). METHODS: This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0-2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov, NCT02357992. FINDINGS: Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9-5·8). Overall survival was 91% (95% CI 85-98) at 3 years and 87% (79-95) at 5 years. SABR was tolerated well, with no grade 4-5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85-98) at 3 years and 84% (76-93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45-1·65], p=0·65) from a multivariable analysis. INTERPRETATION: Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. FUNDING: Varian Medical Systems and US National Cancer Institute (National Institutes of Health).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Radiocirurgia , Cirurgia Torácica Vídeoassistida , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Intervalo Livre de Progressão , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/mortalidade , Texas , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/mortalidade , Fatores de Tempo
19.
Artigo em Inglês | MEDLINE | ID: mdl-34571054

RESUMO

PURPOSE: Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer. METHODS AND MATERIALS: A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles. RESULTS: Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases. CONCLUSIONS: Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data.

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