Phillip J. Koo

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.

On transcending the impasse of respiratory motion correction applications in routine clinical imaging - a consideration of a fully automated data driven motion control framework

Positron emission tomography (PET) is increasingly used for the detection, characterization, and follow-up of tumors located in the thorax. However, patient respiratory motion presents a unique limitation that hinders the application of high-resolution PET technology for this type of imaging. Efforts to transcend this limitation have been underway for more than a decade, yet PET remains for practical considerations a modality vulnerable to motion-induced image degradation. Respiratory motion control is not employed in routine clinical operations. In this article, we take an opportunity to highlight some of the recent advancements in data-driven motion control strategies and how they may form an underpinning for what we are presenting as a fully automated data-driven motion control framework. This framework represents an alternative direction for future endeavors in motion control and can conceptually connect individual focused studies with a strategy for addressing big picture challenges and goals.

Comparison of 4-Dimensional Computed Tomography Ventilation With Nuclear Medicine Ventilation-Perfusion Imaging: A Clinical Validation Study

PURPOSE Four-dimensional computed tomography (4DCT) ventilation imaging provides lung function information for lung cancer patients undergoing radiation therapy. Before 4DCT-ventilation can be implemented clinically it needs to be validated against an established imaging modality. The purpose of this work was to compare 4DCT-ventilation to nuclear medicine ventilation, using clinically relevant global metrics and radiologist observations. METHODS AND MATERIALS Fifteen lung cancer patients with 16 sets of 4DCT and nuclear medicine ventilation-perfusion (VQ) images were used for the study. The VQ-ventilation images were acquired in planar mode using Tc-99m-labeled diethylenetriamine-pentaacetic acid aerosol inhalation. 4DCT data, spatial registration, and a density-change-based model were used to compute a 4DCT-based ventilation map for each patient. The percent ventilation was calculated in each lung and each lung third for both the 4DCT and VQ-ventilation scans. A nuclear medicine radiologist assessed the VQ and 4DCT scans for the presence of ventilation defects. The VQ and 4DCT-based images were compared using regional percent ventilation and radiologist clinical observations. RESULTS Individual patient examples demonstrate good qualitative agreement between the 4DCT and VQ-ventilation scans. The correlation coefficients were 0.68 and 0.45, using the percent ventilation in each individual lung and lung third, respectively. Using radiologist-noted presence of ventilation defects and receiver operating characteristic analysis, the sensitivity, specificity, and accuracy of the 4DCT-ventilation were 90%, 64%, and 81%, respectively. CONCLUSIONS The current work compared 4DCT with VQ-based ventilation using clinically relevant global metrics and radiologist observations. We found good agreement between the radiologists assessment of the 4DCT and VQ-ventilation images as well as the percent ventilation in each lung. The agreement lessened when the data were analyzed on a regional level. Our study presents an important step for the integration of 4DCT-ventilation into thoracic clinical practice.

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.

Parathyroid Imaging: The Importance of Pinhole Collimation with Both Single- and Dual-Tracer Acquisition

Our objective was to rigorously compare pinhole and parallel-hole collimation in an intrapatient, intrastudy design in 2 parathyroid imaging protocols: the first was dual-phase 99mTc-sestamibi imaging, and the second was dual-phase 99mTc-sestamibi plus dual-tracer (99mTc-sestamibi and 123I) simultaneous-acquisition subtraction imaging. Methods: Thirty-three patients with 37 surgically proven nonectopic parathyroid adenomas were evaluated. Anterior pinhole and parallel-hole images of the neck were available for 99mTc-sestamibi at 15 min and 3 h, and for simultaneously acquired 99mTc-sestamibi and 123I subtraction at 15 min, all from a single study. The images were modified so that all had a square border and so that the thyroid filled approximately three quarters of the image. The images were evaluated by 2 experienced nuclear medicine physicians who did not know the surgical results or whether the images were acquired with pinhole or parallel-hole collimation. The observers indicated the location of any identified adenoma and graded the certainty of diagnosis on a 3-point scale. Results: The localization success rate for the 2 observers combined for the single-tracer dual-phase images was 66.2% with pinhole collimation and 43.2% with parallel-hole collimation (P < 0.0001). The localization success rate with the addition of the dual-tracer simultaneous-acquisition subtraction image was 83.8% with pinhole collimation and 62.2% with parallel-hole collimation (P = 0.0018). In addition, the degree of certainty of localization was greater with pinhole collimation with both imaging protocols (P < 0.001 in both cases). Conclusion: In the anterior projection, pinhole collimation is superior to parallel-hole collimation for parathyroid imaging with either dual-phase 99mTc-sestamibi or dual-phase 99mTc-sestamibi plus dual-tracer (99mTc-sestamibi and 123I) simultaneous-acquisition subtraction.

Crizotinib Effects on Creatinine and Non-Creatinine–Based Measures of Glomerular Filtration Rate

Introduction: Rapid reductions in creatinine-based estimates of the glomerular filtration rate (GFR) have recently been reported secondary to crizotinib use. Whether these reflect drug-induced changes in the true GFR or the validity of creatinine as a measure of kidney function in the presence of crizotinib is unknown. Methods: Two anaplastic lymphoma kinase–rearranged non–small-cell lung cancer patients (one with pre-existing renal impairment) were identified during periods of time on and off crizotinib. Creatinine- and iothalamate-based estimates of renal function were conducted in the presence and absence of crizotinib. Results: Crizotinib is associated with both acute and chronic effects on kidney function. Chronic creatinine changes seem to reflect a true reduction in the GFR. In contrast, acute effects include a reduction in creatinine-based estimates of the GFR without a reduction in non-creatinine–based measurements (consistent with, e.g., an acute effect of crizotinib on creatinine secretion), in addition to some reduction in the true GFR (with this latter effect seeming to be more prominent in the presence of pre-existing renal impairment). Conclusion: If crizotinib-associated changes in creatinine-based kidney function suggest a change in dosing with either crizotinib or concomitant medications that are renally excreted, use of a non-creatinine–based assessment of kidney function, such as iothalamate assessments, should be considered before making a final decision.

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.

Anti-CTLA4 antibody therapy related complications on FDG PET/CT.

Anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody therapy is a new class of drug which has demonstrated increased overall survival in patients with metastatic melanoma. Anti-CTLA-4 antibody therapy inhibits the CTLA-4 inhibitory signal, thereby enhancing the anti-tumor response of the cytotoxic T lymphocytes. This response can lead to a variety of immune-related adverse events. Many of these events are present on follow-up PET/CT examinations performed to assess response to therapy. It is important for the interpreting physician to be aware of the findings on PET/CT to avoid diagnosing adverse events as progressive disease and to alert clinicians regarding these complications.

The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II)

OBJECTIVE To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific castration-resistant prostate cancer (CRPC) treatments. MATERIALS AND METHODS The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for metastatic CRPC based on available data and clinical experience. RESULTS A consensus was developed to address important questions on management of patients with metastatic CRPC. CONCLUSION In the absence of large-scale clinical trials, the Working Group recommends that patients may best be managed with a layered approach of approved therapies with unique or complimentary mechanisms of action.

Case 146: Benign Multicystic Mesothelioma

History A 27-year-old gravida 1, para 1 woman who had a history of pelvic inflammatory disease presented to the emergency department with lower abdominal pain, nausea, vomiting, and chills. She began menstruating the night before presentation and reported an acute exacerbation of her chronic abdominal pain, which typically worsened with her menses. Her surgical history included one caesarean section and laparoscopic excision of a tubo-ovarian abscess. She was afebrile. Physical examination revealed mild diffuse abdominal tenderness and tenderness of the cervix. Laboratory findings revealed a white blood cell count of 17 000 cells per cubic millimeter. (A normal white blood cell count is between 4800 and 11 000 cells per cubic millimeter.) Ultrasonography (US) of the pelvis was performed. A computed tomographic (CT) examination of the abdomen and pelvis was subsequently performed after intravenous administration of 125 mL of iohexol (Omnipaque; Amersham Health, Princeton, NJ). We acquired 5-mm axial sections and performed 3-mm coronal reconstruction.