Jennifer J. Kwak

Cancer Immunotherapy: Imaging Assessment of Novel Treatment Response Patterns and Immune-related Adverse Events

Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression.

Validation of Software Gating: A Practical Technology for Respiratory Motion Correction in PET

Purpose To assess the performance of hardware- and software-gating technologies in terms of qualitative and quantitative characteristics of respiratory motion in positron emission tomography (PET) imaging. Materials and Methods Between 2010 and 2013, 219 fluorine 18 fluorodeoxyglucose PET examinations were performed in 116 patients for assessment of pulmonary nodules. All patients provided informed consent in this institutional review board-approved study. Acquisitions were reconstructed as respiratory-gated images by using hardware-derived respiratory triggers and software-derived signal (via an automated postprocessing method). Asymmetry was evaluated in the joint distribution of reader preference, and linear mixed models were used to evaluate differences in outcomes according to gating type. Results In blind reviews of reconstructed gated images, software was selected as superior 16.9% of the time (111 of 657 image sets; 95% confidence interval [CI]: 14.0%, 19.8%), and hardware was selected as superior 6.2% of the time (41 of 657 image sets; 95% CI: 4.4%, 8.1%). Of the image sets, 76.9% (505 of 657; 95% CI: 73.6%, 80.1%) were judged as having indistinguishable motion quality. Quantitative analysis demonstrated that the two gating strategies exhibited similar performance, and the performance of both was significantly different from that of nongated images. The mean increase ± standard deviation in lesion maximum standardized uptake value was 42.2% ± 38.9 between nongated and software-gated images, and lesion full width at half maximum values decreased by 9.9% ± 9.6. Conclusion Compared with vendor-supplied respiratory-gating hardware methods, software gating performed favorably, both qualitatively and quantitatively. Fully automated gating is a feasible approach to motion correction of PET images. (©) RSNA, 2016 Online supplemental material is available for this article.

Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma.

PurposeMetabolic response to treatment measured by fluorine-18 fluorodeoxyglucose (18F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on 18F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy. Materials and methodsOverall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with 18F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax. ResultsThe mean time to follow-up 18F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06–1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42–97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23–189.42, P=0.002). ConclusionChange in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.

PD-1 Blockade in Mediastinal Gray-Zone Lymphoma

Mediastinal gray-zone lymphoma is intermediate between classic Hodgkin’s lymphoma and primary mediastinal B-cell lymphoma. Three patients whose disease had become refractory to chemotherapy had impressive responses to PD-1 blockade.

Novel Imaging of Prostate Cancer with MRI, MRI/US, and PET

Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PET on the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer.

Frequency based gating: An alternative, conformal, approach to 4D PET data utilization

PURPOSE Respiratory gating is a strategy for overcoming image degradation caused by patient motion in Positron Emission Tomography (PET) imaging. Traditional methods for sorting data, namely, phase-based gating or amplitude-based gating, come with an inherent trade-off between resolution improvements and added noise present in the subjugated data. If the goal of motion correction in PET is realigned from creating 4D images that attempt to mimic nongated images, towards ideal utilization of the information available, then new paths for data management emerge. In this work, the authors examine the application of a method in a new class of frequency based data subjugation algorithms, termed gating +. This strategy utilizes data driven information to locally adapt signal to its optimal segregation, thereby creating a new approach to 4D data utilization PET. METHODS 189 (18)F-fluorodeoxyglucose (FDG) PET scans were acquired at a single bed position centered on the thorax region. 4D gated image sets were reconstructed using data driven gating. The gating+ signal optimization algorithm, previously presented in small animal PET images and simulations, was used to segregate data in frequency space to generate optimized 4D images in the population-the first application and analysis of gating+ in human PET scans. The nongated, phase gated, and gating+ representations of the data were compared using FDG uptake analysis in the identified lesions and noise measurements from background regions. RESULTS Optimized processing required less than 1 min per scan on a standard PC (plus standard reconstruction time), and yielded entire 4D optimized volumes plus motion maps. Optimized scans had noise characteristics similar to nongated images, yet also contained much of the resolution and motion information found in the gated images. The average SUVmax increase in the lesion sample between gated/nongated and gating+/nongated (±SD in population) was 35.8% ± 34.6% and 28.6% ± 27.9%, respectively. The average percent standard deviation (%SD ± SD in population) in liver volumes of interest (VOIs) across the sample for the nongated, gated, and gating+ scans was 6.7% ± 2.4%, 13.6% ± 3.3%, and 7.1% ± 2.5%, respectively. In all cases, the noise in the gating+ liver VOIs was closer to the nongated measurements than to the gated. CONCLUSIONS The gating+ algorithm introduces the notion of conforming 4D data segregation to the local information and statistics that support it. By segregating data in frequency space, the authors are able to generate low noise motion information rich image sets, derived solely from selective use of raw data. Their work shows that the gating+ algorithm can be robustly applied in populations, and across varying qualities of motion and scans statistics, and be integrated as part of a fully automated motion correction workflow. Furthermore, the idea of smart signal utilization underpins a new concept of low risk or even risk-free motion correction application in PET.

Interim Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Pathologic Response to Preoperative Chemoradiotherapy and Prognosis in Patients With Locally Advanced Rectal Cancer.

INTRODUCTION The goal of the present study was to investigate the predictive and prognostic values of interim fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters for the prediction of a complete pathologic response (pCR) in patients with locally advanced rectal cancer (LARC) who had received preoperative chemoradiotherapy (PCRT). PATIENTS AND METHODS A total 103 patients with LARC were included in the present study. All the patients were evaluated by 18F FDG PET/CT before and after 45 Gy of radiotherapy with concurrent oral capecitabine chemotherapy. The quantitative, volumetric parameters and their percentage of change (Δ%) were used to predict the pCR and calculate the overall survival (OS). The predictive value for a pCR of 18F FDG PET/CT cutoff values were determined by receiver operating characteristic analysis. The prognostic significance was assessed using Kaplan-Meier analysis. RESULTS A pCR occurred in 22 patients (21.4%). Univariate and multivariate analyses demonstrated that the post-PCRT maximum standardized uptake value (SUVmax2) and change in the SUVmax (ΔSUVmax) as significant factors for the prediction of pCR, with a sensitivity of 68.2% and specificity of 87.7% and sensitivity of 90.9% and specificity of 80.3%, respectively. Kaplan-Meier analysis showed that a low SUVmax2 (< 2.5) and high ΔSUVmax (≥ 62.2%) were potent predictors for OS. CONCLUSION The present study has shown the capability of interim 18F FDG PET/CT parameters to predict the achievement of pCR after PCRT in patients with LARC. Of the parameters, SUVmax2 and ΔSUVmax were potent predictors for pCR and well associated with OS.

Implications of Sentinel Lymph Node Drainage to Multiple Basins in Head and Neck Melanoma

BackgroundSentinel lymph node biopsy (SLNB) for head and neck melanoma is challenging due to unpredictable drainage. We sought to determine the frequency of drainage to multiple lymphatic basins and asked if this was associated with prognosis in a large, single-center cohort.MethodsWe queried patients diagnosed with head and neck melanomas who had a SLNB performed from January 1998 to April 2016. Demographic and clinical characteristics were compared using Student’s t test, Pearson chi-square analysis, log-rank test, Wilcoxon-Mann–Whitney test, and Kaplan–Meier curves.ResultsWe identified 269 patients with head and neck melanoma that had SLNBs performed in the following locations: 223 neck, 92 parotid/preauricular, 29 occipital/posterior auricular, 1 axilla. There were 68 (25%) patients who had drainage to multiple basins. These patients were similar to those with single basin drainage in age, gender distribution, Breslow depth, and percent with a positive SLNB (all p > 0.05). Fewer patients with drainage to multiple basins had a completion lymph node dissection (CLND, p = 0.03). A trend toward increased 3-year locoregional recurrence was seen for patients with drainage to multiple basins in univariate analysis (27% vs. 18%, p = 0.10) but was lost in multivariate analysis (p = 0.49), possibly because of higher recurrence rates in patients with positive nodes but no CLND (p = 0.02). No difference was detected for distant recurrence or overall survival based on SLN drainage.ConclusionsHead and neck melanoma SLNB drainage to multiple basins is common. Drainage to multiple basins does not seem to be associated with increased sentinel lymph node positivity, locoregional recurrence, distant recurrence, or survival.

Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy

Aims: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). Methods: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. Results: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. Conclusion: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients.

Giant pulmonary chondroid hamartoma: imaging and pathology correlation of a rare tumor demonstrated with bone scintigraphy and 18F-FDG PET/CT

A 35-year-old man presented to the emergency department with a worsening cough and a history of unintended weight loss. Chest radiograph revealed a giant mass occupying the left hemithorax. On CT scan, the mass measured over 20 cm and shifted the heart into the right hemithorax. Bone scan demonstrated multifocal radiotracer uptake within coarse intratumoral calcifications. Biopsy revealed no malignant cells. However, malignancy was clinically suspected due to size, and FDG PET/CT was performed. Mild FDG uptake was present in the mass. The mass was excised, and pathologic examination revealed the rare diagnosis of a giant pulmonary chondroid hamartoma.