Time-of-flight (TOF) positron emission tomography (PET) can improve signal-to-noise ratio (SNR) relative to conventional PET by improving coincidence localization and reducing random coincidences. Several time-of-flight positron emission tomographs were developed in the 1980s and early 1990s. However, interest in time-of-flight waned because of the low stopping power and light yield of the scintillators available at that time. Now newly discovered scintillators with greater light yield and/or stopping power, along with advances in photomultiplier tubes and electronics, are rekindling interest in TOF. To facilitate investigations into the utility of TOF, we have modified the SimSET simulation to track and bin TOF differences between coincidence photons. Images were reconstructed from simulated data using confidence-weighted backprojection and filtered backprojection. These images were used to investigate the effect of TOF on SNR. SNR improves dramatically with improved TOF resolution. However, the improvement is somewhat less than that predicted by a widely used theoretical model.
to higher dose, at least 50Gy in 4 fractions. The primary endpoint was pergroup cumulative incidence of local recurrence at 1 year (recurrence of treated tumor within same lobe), with distant recurrence and death as competing risks. Treated tumor recurrence (recurrence with epicenter within 1cm of PTV) and toxicity were also analyzed. Results: A total of 217 patients were enrolled from 2011-2018 (some patients were enrolled multiple times). Median age was 72, 59% were male, and 69% were current/former smokers. There were 240 treatment courses and 285 tumors treated (range 1-3 tumors per course). 211 tumors were peripheral and 74 were central. Tumor size distribution was: ≤10cc, 74%; 10-30cc, 19%; > 30cc, 7%. The most common dose was 25Gy in one fraction (158 tumors). Median follow-up was 30 months (range 2-95). Median overall survival was 57 months. Local recurrence data are currently being updated and will be presented at the meeting. The rate of grade 2 or higher pneumonitis was 16/217 (7%) and grade 3 or higher pneumonitis was 3/217 (1%). The rate of grade 2 or higher chest wall pain was 13/217 (6%). One patient had a grade 5 adverse event, developing pulmonary hemorrhage that was possibly related to radiotherapy, 17 months after treatment of a large central NSCLC. Conclusion: Individualized SABR to lung cancers resulted in excellent local control and favorable toxicity profile.
Background: Using quantitative FDG PET to measure glucose metabolism and perfusion, and dynamic contrast-enhanced (DCE) MRI to measure perfusion, we previously identified a metabolic signature for breast cancer resistant to NAC. This imaging signature is (1) persistent or increased tumor perfusion despite treatment, (2) an altered pattern of glucose kinetics in response to therapy, and (3) pre-therapy mismatch between tumor metabolism (MRFDG) and glucose delivery (K1) (high ratio of MRFDG/K1). These patterns predict poor response, early relapse and death independent of established prognostic factors, including pathologic response. Identification of factors associated with resistance or response to therapy is the translational goal of "Quantitative Dynamic PET and MRI in Breast Cancer Therapy," part of the Seattle Breast SPORE (1P50CA138293). Methods: Patients (Pts) undergoing NAC for histologically confirmed breast cancer (stage II-III) were approached for this trial (CCIRB# 7587). FDG PET and DCE-MRI were obtained pre-therapy, 2-12 weeks after start of NAC (mid-therapy) and after completion of NAC. Breast biopsies were obtained pre-therapy and post-NAC. FDG PET included a dynamic scan with kinetic analysis. PET measures included SUVmax, MRFDG, K1, Ki, and Patlak. 3T DCE-MRI measurements included semi-quantitative vascular parameters of peak enhancement (PE), signal enhancement ratio (SER), washout fraction, functional tumor volume, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI (DWI). Breast biopsies were assayed by immunohistochemistry and gene expression profiling. NAC was per physician's choice with most pts receiving weekly paclitaxel (with trastuzumab if HER2+) followed by doxorubicin/cyclophosphamide. Results: 32 pts have completed the study. Pathologic complete response (pCR), defined as absence of invasive cancer in the breast, was observed in 9 (28%); near pCR defined as only microscopic residual invasive cancer in 3 (9%) more pts. Mid-therapy decline in SUVmax and K1 was associated with near pCR; (p-value 0.06, 0.04, respectively). Pre-therapy PET measures of MRFDG and K1 were not predictive of pCR. On MRI, pre-therapy PE (p=0.009), SER (p=0.01), washout fraction (p=0.02), ADC (p=0.08, trend) and mid-therapy change in volume (p=0.05) were each predictive of pCR. Gene profiling of pre-therapy biopsies showed correlation between high MRFDG/K1 ratio in basal and luminal B tumors. Conclusions: Assessment of serial changes in tumor metabolism and perfusion by FDG PET and DCE-MRI is feasible in the clinic. Mid-therapy decline in metabolism and glucose delivery was predictive of pCR; consistent with prior retrospective series. Baseline DCE-MRI and DWI measures show promise to predict response, and associations of mid-therapy change in MR functional tumor volume with pCR agree with findings of another multisite clinical trial (ISPY). These imaging parameters may serve as useful biomarkers to inform future neoadjuvant trials. Integration of imaging data with gene expression profiling revealed that the pattern of metabolism in luminal B tumors was closer to that of the basal subtype compared to other ER-positive tumors. Citation Format: Specht JM, Partridge S, Chai X, Novakova A, Peterson L, Shields A, Guenthoer J, Linden HM, Gralow JR, Gadi V, Korde L, Hills D, Hsu L, Hockenbery DM, Kinahan P, Mankoff DA, Porter PL. Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-02.
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