Liver Injury in Patients With Distal Esophageal Carcinoma After Precision Radiation Therapy: Systematic Review of FDG-PET/CT Patterns.

OBJECTIVE: To determine the incidence and various patterns of radiation-induced liver injury (RILI) and its temporal evolution on fluorodeoxiglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemoradiation using precision radiation in patients with esophageal carcinoma. MATERIAL AND METHODS: We evaluated 639 patients with locally advanced esophageal carcinoma who had serial FDG-PET/CTs after neoadjuvant chemoradiation. Two readers reviewed the imaging studies in consensus and recorded the cases where new foci of increased FDG uptake were identified within the radiated liver parenchyma. RILI was confirmed by follow-up imaging or percutaneous biopsy. RESULTS: FDG-avid RILI developed in 39/639 (6%) of patients. The caudate and left hepatic lobe were involved in all cases. There were various patterns of increased FDG uptake: 38% of patients had a single focus of increased FDG uptake and 62% had 2 regions of increased FDG uptake, which were focal nodular or diffuse or a combination of focal nodular and diffuse FDG uptake. On CT, 72% of patients had a poorly-marginated region of low attenuation and 28% had a well-defined region of low attenuation with sharp, well-defined linear borders in the location of the radiation, as confirmed by the treatment plan. CONCLUSION: The caudate and left hepatic lobes were involved in all cases of RILI. The various imaging patterns of RILI on FDG-PET/CT include 1 or 2 regions of increased FDG uptake with a nodular, diffuse, or combined appearance. Awareness of this potential complication of radiation therapy and knowledge of the imaging manifestations of RILI is important to avoid misinterpretation as a metastasis.

Clinical Significance of [18F] Fluoro-2-Deoxy-d-Glucose/Computed Tomographic Avid Hilar Lymph Nodes in Esophageal Carcinoma Patients.

BACKGROUND: The assumption that increased [18F] fluoro-2-deoxy-d-glucose (FDG) uptake in hilar nodes on positron emission tomography/computed tomography (PET/CT) imaging is indicative of distant metastasis can result in palliative rather than curative care in patients with esophageal cancer. This study aimed to determine the significance of increased FDG uptake in hilar nodes in patients with potentially curable, locally advanced disease at initial staging. METHODS: We included patients with biopsy specimen-proven esophageal carcinoma who had pretreatment FDG-PET/CT at initial staging and follow-up imaging >1 year. We excluded patients with distant hematogeneous metastases. Hilar nodes were considered concerning for metastatic disease when the maximum standardized uptake value was >2.5 or FDG uptake was visually greater than the mediastinal background. RESULTS: We reviewed FDG-PET CT scans from 806 patients treated for esophageal cancer from 2010 to 2018 and identified 42 patients with FDG-avid hilar adenopathy. Thirteen patients underwent histologic assessment, and 29 were monitored with imaging. None of the 42 patients had distant metastatic disease on the initial workup, and all were treated curatively. In follow-up, 2 of 42 patients eventually manifested hilar nodal metastases after treatment; 1 who had a biopsy specimen-negative hilar node at initial staging and another who did not have a biopsy of the hilar node. CONCLUSIONS: Increased FDG uptake in hilar nodes in patients with localized esophageal cancer was not indicative of nonregional nodal metastasis. Patients in these situations should be approached with curative intent. The need for biopsy of FDG-avid hilar nodes in this cohort should be carefully considered due to the low diagnostic utility.

Pitfalls and Pearls in Esophageal Carcinoma.

The management of patients with esophageal carcinoma (EC) requires accurate clinical staging and post-therapeutic evaluation. Currently, esophagogastroduodenoscopy/endoscopic ultrasound (EGD/EUS), endoscopic ultrasound-fine needle aspiration (EUS-FNA), computed tomography (CT), 18F- fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance (MR) imaging are used for the initial clinical staging, evaluation of therapeutic response and follow-up in patients with EC. However, there are limitations and pitfalls that are commonly encountered when imaging these patients that can limit accurate assessment. Knowledge of the limitations and pitfalls associated with the use of these different imaging modalities is essential in avoiding misinterpretation and guaranteeing the appropriate management for patient with EC.

Ultra-Low Dose Chest CT with Denoising for Lung Nodule Detection.

BACKGROUND: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction. OBJECTIVES: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS). METHODS: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4. RESULTS: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54-88). ULD scan radiation exposure was comparable on average to 3.6-4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04--0.08 vs. 0.08-0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization. CONCLUSIONS: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.

Thymic Epithelial Neoplasms: Tumor-Node-Metastasis Staging.

Thymic epithelial neoplasms are a group of malignant tumors that includes thymoma, thymic carcinoma, and thymic neuroendocrine tumors. Although several staging systems have been developed over the years for use with these cancers, they have been interpreted and implemented in a nonuniform manner. Recently, the International Association for the study of Lung Cancer and the International Thymic Malignancy Interest Group developed a tumor-node-metastasis staging system that has been universally accepted and correlates with patient survival and outcomes. Although pathologic staging is determined by histologic examination of the resected tumor, imaging plays an important role in clinical staging and is important for informing therapeutic decisions.

Esophageal Cancer: Tumor-Node-Metastasis Staging.

Esophageal cancer is an uncommon malignancy that ranks sixth in terms of mortality worldwide. Squamous cell carcinoma is the predominant histologic subtype worldwide whereas adenocarcinoma represents the majority of cases in North America, Australia, and Europe. Esophageal cancer is staged using the American Joint Committee on Cancer and the International Union for Cancer Control TNM system and has separate classifications for the clinical, pathologic, and postneoadjuvant pathologic stage groups. The determination of clinical TNM is based on complementary imaging modalities, including esophagogastroduodenoscopy/endoscopic ultrasound; endoscopic ultrasound-fine-needle aspiration; computed tomography of the chest, abdomen, and pelvis; and fluorodeoxyglucose PET/computed tomography.

Outcomes and toxicities following stereotactic ablative radiotherapy for pulmonary metastases in patients with primary head and neck cancer.

BACKGROUND: Metastatic head and neck cancers (HNCs) predominantly affect the lungs and have a two-year overall survival (OS) of 15% to 50%, if amenable for pulmonary metastasectomy. METHODS: Retrospective review of the two-year local control (LC), local-regional control (LRC) within the same lobe, OS, and toxicity rates in consecutive patients with metastatic pulmonary HNC who underwent stereotactic ablative radiotherapy (SABR) January 2007 to May 2018. RESULTS: Evaluated 82 patients with 107 lung lesions, most commonly squamous cell carcinoma (SCC; 64%). Median follow-up was 20 months (range: 9.0-97.6). Systemic therapy administered in 34%. LC, LRC, and OS rates were 94%, 90%, and 62%. Patients with oligometastatic disease had a higher OS than polymetastatic disease, 72% vs 44% (HR = 0.30, 95% CI: 0.14-0.64; P = .008). OS in oligometastatic non-SCC and SCC were 100% and 66% (P = .03). There were no grade ≥3 toxicities. CONCLUSIONS: Metastatic pulmonary HNCs after SABR have a two-year OS rate comparable to pulmonary metastasectomy.

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure.

BACKGROUND & PURPOSE: Stereotactic ablative radiation therapy (SABR) is an emerging treatment option for patients with pulmonary metastases; identifying patients who would benefit from SABR can improve outcomes. MATERIALS & METHODS: We retrospectively analyzed local failure (LF), distant failure (DF), overall survival (OS), and toxicity in 317 patients with 406 pulmonary metastases treated with SABR in January 2006-September 2017 at a tertiary cancer center. RESULTS: Median follow-up time was 23 months. Primary adrenal, colorectal, sarcoma, or pancreatic ("less responsive") tumors led to high rates of LF. LF rates for patients with less responsive vs. responsive tumors were 4.6% vs. 1.6% at 12 months and 12.8% vs. 3.9% at 24 months (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.11-0.73; Log-Rank P = 0.0087). A nomogram for 24-month local control was created using Cox multivariate factors (surgical history, planning target volume, primary disease site, lung lobe location). Treating patients with ≤3 pulmonary metastases vs. >3 pulmonary metastases was associated with improved 24-month (74.2% vs. 59.3%) and 48-month (47.7% vs. 35.1%) OS (HR 0.66, 95% CI 0.47-0.95; Log-Rank P = 0.043), and reduced 12-month (22.5% vs. 50.8%) and 24-month (31.8% vs. 61.4%) intrathoracic DF (HR 0.53, 95% CI 0.38-0.74; Log-Rank P < 0.0001). The most common toxicity was asymptomatic pneumonitis (14.8%). Six patients had grade 3 events (5 pneumonitis, 1 brachial plexus). CONCLUSIONS: SABR for pulmonary metastases was effective and well tolerated. Irradiating limited intrathoracic sites of disease led to improved OS and intrathoracic DM. Higher SABR doses or surgery could be considered for less radio-responsive primary tumors.

Improved Alignment of PET and CT Images in Whole-Body PET/CT in Cases of Respiratory Motion During CT.

Respiratory motion during the CT and PET parts of a PET/CT scan leads to imperfect alignment of anatomic features seen by the 2 modalities. In this work, we concentrate on the effects of motion during CT. We propose a novel approach for improving the alignment. Methods: Respiratory waveform data were gathered during the CT and PET parts of 28 PET/CT scans of cancer patients with 40 lesions up to 3 cm in size in the lung or upper abdomen. PET list-mode data were reconstructed by 3 reconstruction methods: PET/static (the standard method with no motion correction); PET/ex (a method that calculates a range of expiratory amplitudes from the lowest one to the highest one); and PET/matched (a novel method that uses both waveforms). The 3 methods were compared. The distance between tumor positions in PET and CT were characterized in visual interpretation by physicians as well as quantitatively. Tumor SUVs (SUVmax and SUVpeak) were determined relative to SUV based on the static method. Image noise was evaluated in the liver and compared with PET/static. Results: In visual interpretation, the rate of good alignment was 13 of 21, 13 of 23, and 18 of 21 for the PET/static, PET/ex, and PET/matched methods, respectively, and the mean PET/CT distances were 3.5, 5.1, and 2.8 mm. In visual comparison with PET/ex, the rate of good alignment was increased in 1 of 10 and 7 of 10 cases for PET/static and PET/matched, respectively. SUVmax was on average 21% higher than PET/static when either PET/ex or PET/matched was used. SUVpeak was 12% higher. Image noise in the liver was 15% higher than PET/static for the PET/ex method, and 40% higher for PET/matched; that is, noise was much lower than in gated PET. Conclusion: Acquiring respiratory waveforms both in PET (as in the current state of the art) and in CT (an unusual key step in this approach) has the potential to improve the alignment of PET and CT images. A proposed method for using this information was tested. Improved alignment was demonstrated.

Thoracic Manifestations of Genitourinary Neoplasms and Treatment-related Complications.

Genitourinary (GU) malignancies are a diverse group of common and uncommon neoplasms that may be associated with significant mortality. Metastases from GU neoplasms are frequently encountered in the chest, and virtually all thoracic structures can be involved. Although the most common imaging manifestations include hematogenous dissemination manifesting with peripheral predominant bilateral pulmonary nodules and lymphatic metastases manifesting with mediastinal and hilar lymphadenopathy, some GU malignancies exhibit unique features. We review the general patterns, pathways, and thoracic imaging features of renal, adrenal, urothelial, prostatic, and testicular metastatic neoplasms, as well as provide a discussion of treatment-related complications that might manifest in the chest. Detailed reporting of these patterns will allow the imager to assist the referring clinicians and surgeons in accurate determination of the stage, prognosis, and treatment options available for the patient. Awareness of specific treatment-related complications further allows the imager to enhance patient safety through accurate and timely reporting of potentially life-threatening consequences of therapies.

Recognizing Radiation Therapy-related Complications in the Chest.

Radiation therapy is one of the cornerstones for the treatment of thoracic malignancies. Although advances in radiation therapy technology have improved the delivery of radiation considerably, adverse effects are still common. Postirradiation changes affect the organ or tissue treated and the neighboring structures. Advances in external-beam radiation delivery techniques and how these techniques affect the expected thoracic radiation-induced changes are described. In addition, how to distinguish these expected changes from complications such as infection and radiation-induced malignancy, and identify treatment failure, that is, local tumor recurrence, is reviewed. ©RSNA, 2019.

Determining extent of invasion and follow-up of thymic epithelial malignancies.

Thymic malignancies may exhibit aggressive behavior such as invasion of adjacent structures and involvement of the pleura and pericardium. The role of imaging in the evaluation of primary thymic neoplasms is to properly assess tumor staging, with emphasis on the detection of local invasion and distant spread of disease, correctly identifying candidates for preoperative neoadjuvant therapy. Different imaging modalities are used in the initial investigation of thymic malignancies including chest radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET), in particular with [18F] fluorodeoxyglucose (FDG). At this moment, CT is the most common imaging modality on the assessment of thymic malignancies. MRI has the benefit of no emission of damaging ionizing radiation reducing the radiation dose to the patient when compared with CT. For this reason, MRI has been playing an important role in the evaluation of tumor invasion and follow up imaging studies which becomes even more relevant in young patients or those patients with prior history of radiation therapy.

Pitfalls and Misinterpretations of Cardiac Findings on PET/CT Imaging: A Careful Look at the Heart in Oncology Patients.

Positron emission tomography (PET) computed tomography (CT) with 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) has been established as an effective modality for evaluation of cancer. Interpretations of patterns of physiologic 18F-FDG uptake by the heart is particularly difficult given the wide normal variations of 18F-FDG metabolic activity observed. Atypical patterns of focal or diffuse physiologic cardiac 18F-FDG uptake and post-therapeutic effects after radiation therapy, systemic diseases, or cardiomyopathy may also be confused with malignant disease on 18F-FDG PET/CT. In this article, we review the variations of normal cardiac 18F-FDG uptake observed in oncology patients and the appearances of other patterns of pathologic metabolic activity, related or not related to the malignancy being investigated, that may lead to false-negative and false-positive results.

Evaluation of a novel elastic respiratory motion correction algorithm on quantification and image quality in abdomino-thoracic PET/CT.

Our aim is to evaluate in phantom and patient studies a recently developed elastic motion debluring (EMDB) technique which makes use of all the acquired PET data and compare its performance to other conventional techniques such as phase based gating (PBG) and HDChest (HDC) both of which use fractions of the acquired data. Comparisons were made with respect to static whole-body (SWB) images with no motion correction. Methods: A phantom simulating respiratory motion of the thorax with lung lesions (5 spheres with ID=10- 28 mm) was scanned with 0, 1, 2, and 3 cm motion. Four reconstructions were performed: SWB, PBG, HDC, and EMDB. For PBG, the average (PBGave) and maximum bin (PBGmax) were used. To compare the reconstructions, the ratios of SUVmax (RSmax), SUVpeak (RSpeak), and CNR (RCNR) were calculated with respect to SWB. Additionally, 46 patients with lung or liver tumors < 3 cm diameter were also studied. Measurements of SUVmax, SUVpeak, and contrast-to-noise ratio (CNR) were made for 46 lung and 19 liver lesions. To evaluate image noise, the SUV standard deviation was measured in healthy lung and liver tissue and in the phantom background. Finally, subjective image quality of patient exams was scored on a 5 point scale by four radiologists. Results: In the phantom, EMDB increased SUVmax/SUVpeak over SWB but to a lesser extent than the other reconstruction methodologies. The RCNR for EMDB however was higher than all other reconstructions (0.68 EMDB > 0.54 HDC > 0.41 PBGmax > 0.31 PBGave). Similar results were seen in patient studies. The SUVmax/SUVpeak were higher by 19.3/11.1% EMDB, 21.6/13.9% HDC, 22.8/12.8% PBGave, and 45.6/26.8% PBGmax compared to SWB. Lung/liver noise increased EMDB (3/15%), HDC (35/56%), PBGave (100/170%), and PBGmax (146/219%). CNR increased in lung/liver tumors only for EMDB (18/13%), and decreased for HDC (-14/-23%), PBGave (-39/-63%), and PBGmax (-18/-46%). Average radiologist scores of image quality were SWB (4.0 ± 0.8) > EMDB (3.7 ± 1.0) > HDC (3.1 ± 1.0) > PBG (1.5 ± 0.7). Conclusion: The EMDB algorithm had the least increase in image noise, improved lesion CNR, and had the highest overall image quality score.

Imaging of Radiation Treatment of Lung Cancer.

Radiation therapy is an important modality in the treatment of patients with lung cancer. Recent advances in delivering radiotherapy were designed to improve loco-regional tumor control by focusing higher doses on the tumor. More sophisticated techniques in treatment planning include 3-dimensional conformal radiation therapy, intensity-modulated radiotherapy, stereotactic body radiotherapy, and proton therapy. These methods may result in nontraditional patterns of radiation injury and various radiologic appearances that can be mistaken for recurrence, infection and other lung diseases. Knowledge of radiological manifestations, awareness of new radiation delivery techniques and correlation with radiation treatment plans are essential in order to correctly interpret imaging in these patients.

Lung Cancer: Posttreatment Imaging: Radiation Therapy and Imaging Findings.

In this review, we discuss the different radiation delivery techniques available to treat non-small cell lung cancer, typical radiologic manifestations of conventional radiotherapy, and different patterns of lung injury and temporal evolution of the newer radiotherapy techniques. More sophisticated techniques include intensity-modulated radiotherapy, stereotactic body radiotherapy, proton therapy, and respiration-correlated computed tomography or 4-dimensional computed tomography for radiotherapy planning. Knowledge of the radiation treatment plan and technique, the completion date of radiotherapy, and the temporal evolution of radiation-induced lung injury is important to identify expected manifestations of radiation-induced lung injury and differentiate them from tumor recurrence or infection.

Diagnosing conduit leak after esophagectomy for esophageal cancer by computed tomography leak protocol and standard esophagram: Is old school still the best?

The imaging modalities available to evaluate anastomotic leak complicating esophagectomy include CT-Esophageal Protocol (CTEP) and esophagram. The purpose of this study was to compare the performance of these two modalities, alone or in combination, with the final diagnosis of leak established by endoscopy, surgery and/or the clinical course and evaluate management implications.

18FDG-PET/CT is useful in the follow-up of surgically treated patients with oesophageal adenocarcinoma.

OBJECTIVE: The purpose of this study was to evaluate fludeoxyglucose-positron emission ;tomography/CT's (FDG-PET/CT) performance in the follow ;up of patients with surgically treated oesophageal adenocarcinoma. METHODS: The follow-up FDG-PET/CT scans of 162 consecutive patients with surgically treated oesophageal adenocarcinoma were retrospectively reviewed. Histopathological and/or imaging examinations confirmed recurrent disease. The accuracy, sensitivity, specificity and negative and positive predictive values were calculated. RESULTS: Recurrence occurred in 71 (43%) patients, usually within the first year following surgery (60%) and in more than one site (76%). The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of FDG-PET/CT for anastomotic recurrence were 77, 76, 16, 98 and 76%; for regional nodal recurrence were 88, 85, 43, 97 and 86%; and for distant metastatic recurrence were: 97, 96, 91, 99 and 96%. In 5 of the 42 patients (12%) with distant metastases, the metastatic sites were outside the area covered by a conventional follow-up chest-abdomen CT and in 4 patients (9%) metastases were barely perceptible on the CT component of the FDG-PET/CT and consequently were unlikely to be detected without the aid of the FDG uptake. CONCLUSION: FDG PET/CT is accurate in detecting oesophageal adenocarcinoma recurrence, especially within the first post-operative year when most recurrences occur, and is useful in identifying patients with a solitary metastasis. Advances in knowledge: FDG-PET/CT should be considered as a valuable tool in the routine follow ;up of surgically treated oesophageal cancer patients within the first 2 years after surgery.

Phase I Dose-Escalation Study of Anti-CTLA-4 Antibody Ipilimumab and Lenalidomide in Patients with Advanced Cancers.

Preclinical data suggest that combining a checkpoint inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose-escalation study using a 3 + 3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase II dose (R2PD) and dose-limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3 mg/kg intravenously every 28 days × 4) and lenalidomide (10-25 mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers. Total of 36 patients (Hodgkin lymphoma, 7; melanoma, 5; leiomyosarcoma, 4; renal cancer, 3; thyroid cancer, 3; other cancers, 14; median of 3 prior therapies) were enrolled. The MTD has not been reached and ipilimumab 3 mg/kg and lenalidomide 25 mg have been declared as R2PD. DLT were grade (G) 3 rash (3 patients) and G3 pancreatitis (1 patient). G3/4 drug-related toxicities other than DLT were G3 anemia (5 patients), G3 thromboembolism (2 patients), G3 thrombocytopenia, G3 rash, G3 hypopituitarism, G3 pneumonitis, G3 transaminitis, and G4 hypopituitarism (all in 1 patient). Eight patients had tumor shrinkage per immune-related response criteria (-79% to -2%) including a PR (-79% for 7.2+ months) in a refractory Hodgkin lymphoma. Using comprehensive genomic profiling, a total mutation burden (mutations/Mb) was evaluated in 17 patients, with one of the patients achieving a PR demonstrated intermediate mutation burden. In conclusion, combination of ipilimumab and lenalidomide is well tolerated and demonstrated preliminary signals of activity in patients with refractory Hodgkin lymphoma and other advanced cancers. Mol Cancer Ther; 17(3); 671-6. ©2017 AACR.

Positron Emission Tomography/Computed Tomography in Esophageal Carcinoma: Applications and Limitations.

Squamous cell carcinoma and adenocarcinoma represent approximately 98% of esophageal malignant tumors. During the last 30 years, the incidence of adenocarcinoma has increased in Western countries (including the USA) where adenocarcinoma currently represents more than 60% of esophageal malignancies, although, worldwide, squamous cell carcinoma continues to be the predominant histologic type. Integrated positron emission tomography or computed tomography with 2-[fluorine18] fluro-2-deoxy-d-glucose is used in many institutions routinely as a tool in the initial staging and then repeated after therapy for the assessment of response to neoadjuvant therapy and detection of recurrent disease in patients with esophageal carcinoma. As with any other imaging modality, 2-[fluorine18] fluro-2-deoxy-d-glucose-positron emission tomography or computed tomography has strengths and limitations that should be understood in order to maximize its utility.