Purpose
To investigate whether imaging features from pretreatment planning CT scans are associated with overall survival (OS), recurrence‐free survival (RFS), and loco‐regional recurrence‐free ...survival (LR‐RFS) after stereotactic body radiotherapy (SBRT) among nonsmall‐cell lung cancer (NSCLC) patients.
Patients and methods
A total of 92 patients (median age: 73 yr) with stage I or IIA NSCLC were qualified for this study. A total dose of 50 Gy in five fractions was the standard treatment. Besides clinical characteristics, 24 “semantic” image features were manually scored based on a point scale (up to 5) and 219 computer‐derived “radiomic” features were extracted based on whole tumor segmentation. Statistical analysis was performed using Cox proportional hazards model and Harrell's C‐index, and the robustness of final prognostic model was assessed using tenfold cross validation by dichotomizing patients according to the survival or recurrence status at 24 months.
Results
Two‐year OS, RFS and LR‐RFS were 69.95%, 41.3%, and 51.85%, respectively. There was an improvement of Harrell's C‐index when adding imaging features to a clinical model. The model for OS contained the Eastern Cooperative Oncology Group (ECOG) performance status Hazard Ratio (HR) = 2.78, 95% Confidence Interval (CI): 1.37–5.65, pleural retraction (HR = 0.27, 95% CI: 0.08–0.92), F2 (short axis × longest diameter, HR = 1.72, 95% CI: 1.21–2.44) and F186 (Hist‐Energy‐L1, HR = 1.27, 95% CI: 1.00–1.61); The prognostic model for RFS contained vessel attachment (HR = 2.13, 95% CI: 1.24–3.64) and F2 (HR = 1.69, 95% CI: 1.33–2.15); and the model for LR‐RFS contained the ECOG performance status (HR = 2.01, 95% CI: 1.12–3.60) and F2 (HR = 1.67, 95% CI: 1.29–2.18).
Conclusions
Imaging features derived from planning CT demonstrate prognostic value for recurrence following SBRT treatment, and might be helpful in patient stratification.
Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients ...receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified. Radiation was administered prior to, during and after anti-PD-1/PD-L1 therapy in 22 lesions (45%), 13 lesions (27%), and 14 lesions (29%), respectively. The 6 months Kaplan–Meier (KM) distant brain control rate was 48% following stereotactic radiation. Six and 12 month KM rates of OS from the date of stereotactic radiation and the date of cranial metastases diagnosis were 48/41% and 81/51%, respectively. The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). A Karnofsky Performance Status (KPS) of <90 was found to be predictive of worse OS following radiation treatment on both univariate and multivariate analyses (MVA, p = 0.01). In our series, stereotactic radiation to NSCLC brain metastases was well tolerated in patients who received anti-PD-1/PD-L1 therapy. Prospective evaluation to determine how these two modalities can be used synergistically to improve distant brain control and OS is warranted.
TITAN (TRIUMF's Ion Trap for Atomic and Nuclear science) is a system of multiple ion traps installed at the radioactive ion beam facility ISAC. The uniqueness of the system lies in the combination of ...different kinds of ion traps nowhere else available, and the coupling of this system to ISAC as a source of the most intense radioactive beams of very exotic nuclei worldwide. ISAC is now been operational for more than 5 years, and has been proven to be able to deliver a broad variety of radioactive species with unsurpassed production yields, making it the facility of choice for a next generation ion trap facility, like TITAN.
The physics goals of TITAN are manifold, but the emphasis lies on the test of the Standard Model via the determination of the
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ud CKM matrix element, nuclear structure and halo-nuclei investigations, and nuclear astrophysics by providing precise and accurate mass measurements.
Outcome modeling plays an important role in personalizing radiotherapy and finds applications in specialized areas such as adaptive radiotherapy. Conventional outcome models that are based on a ...simplified understanding of radiobiological effects or empirical fitting often only consider dosimetric information. However, it is recognized that response to radiotherapy is multi-factorial and involves a complex interaction of radiation therapy, patient and treatment factors, and the tumor microenvironment. Recently, large pools of patient-specific biological and imaging data have become available with the development of advanced biotechnology and multi-modality imaging techniques. Given this complexity, artificial intelligence (AI) and machine learning (ML) are valuable to make sense of such a plethora of heterogeneous data and to aid clinicians in their decision-making process. The role of AI/ML has been demonstrated in many retrospective studies and more recently prospective evidence has been emerging as well to support AI/ML for personalized and precision radiotherapy.
Multiple-reflection time-of-flight mass spectrometers (MR-TOF-MS) have been demonstrated to have a mass resolving power in the range of few hundreds of thousand. The TITAN MR-TOF-MS has been used to ...separate isobaric impurities and measure masses of many rare isotopes. Recently we have measured the mass and half-lives of neutron-rich Rubidium isotopes with the MR-TOF-MS. This technique is capable of measuring the half-life of rare isotopes in the range of few tens of millisecond. In this proceeding, we present the measurement of half-life of 100Rb that was found to be 50±5 ms, in good agreement with literature value of 48±3 ms.
Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced ...non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab.
Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-"dry" IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR).
From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board-approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications.
Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.
An ion beam cooler and buncher has been developed for the manipulation of radioactive ion beams. The gas-filled linear radiofrequency ion trap system is installed at the Penning trap mass ...spectrometer ISOLTRAP at ISOLDE/CERN. Its purpose is to accumulate the 60-keV continuous ISOLDE ion beam with high efficiency and to convert it into low-energy low-emittance ion pulses. The efficiency was found to exceed 10% in agreement with simulations. A more than 10-fold reduction of the ISOLDE beam emittance can be achieved. The system has been used successfully for first on-line experiments. Its principle, setup and performance will be discussed.
Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and ...nivolumab (NIVO) after TRT would improve outcomes for patients with extensive stage small cell lung cancer.
Eligibility required stable disease or better after platinum doublet chemotherapy. Study therapy included consolidative TRT to 30 Gy in 10 fractions, targeting residual primary tumor and initially involved regional lymph nodes. Two weeks after TRT, patients received concurrent IPI (3 mg/kg) and NIVO (1 mg/kg) every 3 weeks for 4 doses followed by NIVO monotherapy (480 mg) every 4 weeks until progression or up to 1 year.
The study enrolled 21 patients, with 6-month progression-free survival (PFS) of 24% (90% confidence interval CI, 11%-40%) and a median PFS of 4.5 months (95% CI, 2.7%-4.6%). The 12-month overall survival (OS) was 48% (95% CI, 29%-64%) with a median OS of 11.7 months (95% CI, 4.7%-16.0%). Fifty-two percent of patients had ≥1 possibly related grade 3 to 4 immune-related adverse event. Grade 3 pulmonary and gastrointestinal immune-related adverse events were recorded in 19% and 24% of patients, respectively. Exploratory analysis showed increased cytotoxic T cell (CD3+CD8+) tumor infiltration was associated with favorable PFS (P = .01) and OS (P = .02). Reduction in peripheral blood CD3+CD8+ from baseline to after first dose of IPI/NIVO was associated with improved PFS (P = .02) and OS (P = .02).
Consolidative IPI and NIVO after platinum-based chemotherapy and TRT demonstrated a toxicity profile consistent with the known adverse events attributable to IPI and NIVO. Although the study regimen did not significantly improve PFS, the OS was higher than historic expectations. CD3+CD8+ tumor infiltration and migration may identify patients most likely to have improved outcomes in small cell lung cancer.
The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant ...(also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.
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