几何不确定性鲁棒优化在肝癌立体定向放疗中的应用

目的:分析基于几何不确定性的鲁棒优化计划对肝癌立体定向放疗（SBRT）剂量分布的影响。方法:选取12例肝癌SBRT患者，对每例制作3个调强计划:①基于PTV（ITV-PTV 5 mm）的常规优化（PTV-Based Plan）；②基于ITV非均匀几何不确定性（本中心计算的不确定性值:进出方向7 mm，左右和前后方向4 mm）的鲁棒优化（Robust Planactual）；③基于ITV均匀5 mm几何不确定性的鲁棒优化（Robust Plan5 mm）。所有计划都以95%的PTV满足处方剂量作为目标，以等中心均匀偏移4、5、7 mm计算扰动剂量评估鲁棒性。结果:计划①②③的均匀性指数（HI）分别为0.083±0.027、0.099±0.035、0.096±0.026，不具有统计学意义；计划①②③的适形性指数（CI）分别为0.98±0.02、1.02±0.05、1.00±0.04，计划②③相对于计划①的CI具有统计学意义。计划③的正常肝组织平均受量和V2500相对于计划①②分别下降了4.1%、2.5%和5.4%、3.0%，且具有统计学意义（P=0.034、P=0.021和P=0.004、P=0.004），计划②相对于计划①的正常肝组织平均受量和V2500不具有统计学意义（P=0.308和P=0.182），但下降了1.6%和2.5%。对于其鲁棒性，计划②③的5 mm-D99%、5 mm-D98%、5 mm-D95%的剂量-体积直方图带宽（DVHBW）差值相对于计划①更小，随着摆位不确定度的增大，其DVHBW差值越大。结论:在肝脏SBRT治疗中，采用鲁棒优化能够提高靶区剂量分布质量，即使在摆位不确定度有所增加的情况下，仍可以保证ITV的剂量覆盖同时不增加正常组织的照射剂量。     

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Microwave Ablation versus Stereotactic Body Radiotherapy for Stage I Non–Small Cell Lung Cancer: A Cost-Effectiveness Analysis

PurposeTo assess the cost effectiveness of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) for patients with inoperable stage I non–small cell lung cancer (NSCLC).Materials and MethodsA literature search was performed in MEDLINE with broad search clusters. A decision-analytic model was constructed over a 5-year period. The model incorporated treatment-related complications and long-term recurrence. All clinical parameters were derived from the literature with preference to long-term prospective trials. A healthcare payers’ perspective was adopted. Outcomes were measured in quality-adjusted life years (QALYs) extracted from prior studies and U.S. dollars from Medicare reimbursements and prior studies. Base case calculations, probabilistic sensitivity analysis with 10,000 Monte Carlo simulations, and multiple 1- and 2-way sensitivity analyses were performed.ResultsMWA yielded a health benefit of 2.31 QALYs at a cost of $195,331, whereas SBRT yielded a health benefit of 2.33 QALYs at a cost of $225,271. The incremental cost-effectiveness ratio was $1,480,597/QALY, indicating that MWA is the more cost-effective strategy. The conclusion remains unchanged in probabilistic sensitivity analysis with MWA being the optimal cost strategy in 99.84% simulations. One-way sensitivity analyses revealed that MWA remains cost effective when its annual recurrence risk is <18.4% averaged over 5 years, when the SBRT annual recurrence risk is >1.44% averaged over 5 years, or when MWA is at least $7,500 cheaper than SBRT.ConclusionsMWA appears to be more cost effective than SBRT for patients with inoperable stage I NSCLC.     

Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go?

Following adoption of moderately hypofractionated radiotherapy as a standard for localised prostate cancer, ultrahypofractioned radiotherapy delivered in five to seven fractions is rapidly being embraced by clinical practice and international guidelines. However, the question remains: how low can we go? Can radiotherapy for prostate cancer be delivered in fewer than five fractions? The current review summarises the evidence that radiotherapy for localised prostate cancer can be safely and effectively delivered in fewer than five fractions using high dose rate brachytherapy or stereotactic body radiotherapy. We also discuss important lessons learned from the single-fraction high dose rate brachytherapy experience.     

Executive summary from American Radium Society’s appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases

BackgroundThe American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines.MethodsThe panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.ResultsThe panel agreed that SRS alone is usually appropriate for those with good performance status and 2–10 asymptomatic BM, and usually not appropriate for >20 BM. For 11–15 and 16–20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2–4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options.ConclusionsFor patients with 2–10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.     

肺癌脑转移放射治疗方式及进展

肺癌是发病率和死亡率最高的恶性肿瘤，其脑转移发生率高且预后差。近年来随着靶向以及免疫治疗药物相继研制成功，肺癌原发灶局部控制率得以提升，因此对其脑转移的治疗更加关注。放射治疗是肺癌脑转移治疗的重要手段之一，现将肺癌脑转移放射治疗方式及进展进行综述。     

New evidence supporting lung cancer screening with low dose CT & surgical implications

IntroductionLung cancer is the leading cause of cancer-death worldwide. The U.S. Preventative Services Task Force (USPTSF) approved screening for current or former smokers aged 55–80 based on the results of the National Lung Screening trial (NLST). Following the NLST, new evidence has emerged from clinical trials and updates to previous trials prior to the anticipated update to the USPSTF guideline. We review the new evidence on lung cancer screening with low dose computed tomography (LDCT) and the surgical implications.MethodsA review of new literature was performed pertaining to lung cancer screening since implementation of UPSTF guidelines. Articles for inclusion were identified by both authors’, then search of the Pubmed and Cochrane database was performed from January 1st, 2013 through February 4th, 2020 using the MeSH search terms: “lung cancer”; “screening”; “low dose CT”. The results of these studies are summarized.ResultsWe identified multiple prospective randomized control trials and meta-analysis since the NLST supporting lung cancer-specific mortality with screening. We identified new nodule classification systems and the development of risk-models which may reduce false positive rates and identify high risk patients not currently eligible for screening. Finally, we discussed the surgical implications of screening.ConclusionNew data supports NLST findings and show ongoing benefit to LDCT for lung cancer screening. Standardized LDCT screening classification has been shown to reduce harm and lower false positive rates. Further study is needed regarding use of risk-modeling. Screening will require an increase in the thoracic workforce to accommodate the amount of surgically operable cancers.