Diagnostic Chest CT Research Articles

The role of lung cancer risk and comorbidity in lung cancer screening use

Although lung cancer screening (LCS) with low dose computed tomography has been shown to reduce lung cancer mortality, benefits and harms of screening vary among eligible adults. The goal of this study was to evaluate whether LCS is more commonly used among populations most likely to benefit, namely adults with high lung cancer risk and low comorbidity. In this cohort study of patients eligible for LCS, we used data from the electronic health record to evaluate the relationship between lung cancer risk, comorbidity, and receipt of LCS. We also evaluated use of diagnostic chest CT. Analyses used a nonparametric test for trend across quartiles of lung cancer risk and comorbidity. The study sample included 551 LCS-eligible adults who were followed for a mean 2.9 years (SD 1.6 years). A cumulative 190 (34 %) received at least 1 LCS, and 141 (26 %) had a diagnostic chest CT. Receipt of LCS increased across quartiles of lung cancer risk (5 per 100 person years in the lowest quartile vs 13 per 100 person-years in the highest, p < 0.001 for test of trend). LCS receipt decreased across increasing quartiles of comorbidity (14 vs 8 per 100 person-years, p = 0.008). Diagnostic CT was more common in among patient with higher levels of comorbidity (15 vs 5 per 100 person-years, p < 0.001). In conclusion, lung cancer screening was more commonly used in patients with greater lung cancer risk and lower comorbidity. Results suggest that both patient characteristics and use of diagnostic imaging may shape current patterns of LCS use.

Hospitalization as an opportunity to engage underserved individuals in shared decision-making for lung cancer screening: results from two randomized pilot trials.

Medicare requires tobacco dependence counseling and shared decision-making (SDM) for lung cancer screening (LCS) reimbursement. We hypothesized that initiating SDM during inpatient tobacco treatment visits would increase LCS among patients with barriers to proactively seeking outpatient preventive care. We collected baseline assessments and performed two pilot randomized trials at our safety-net hospital. Pilot 1 tested feasibility, acceptability, and preliminary efficacy of a nurse practitioner initiating SDM for LCS during hospitalization (Inpatient SDM). We collected qualitative data on barriers encountered during Pilot 1. Pilot 2 added a community health worker (CHW) to address barriers to LCS completion (Inpatient SDM + CHW-navigation). For both studies, preliminary efficacy was an intention-to-treat analysis of LCS completion at 3months between intervention and comparator (furnishing of LCS decision aid only) groups. Baseline assessments showed that patients preferred in-person LCS discussions versus self-reviewing materials; overall 20% had difficulty understanding written information. In Pilot 1, 4% (2/52) in Inpatient SDM versus 2% (1/48, comparator) completed LCS (p = 0.6), despite 89% (89/100) desiring LCS. Primary care providers noted that competing priorities and patient factors (e.g., social barriers to keeping appointments) prevented the intervention from working as intended. In Pilot 2, 50% (5/10) in Inpatient SDM + CHW-navigation versus 9% (1/11, comparator) completed LCS (p < 0.05). Many patients were ineligible due to recent diagnostic chest CT (Pilot 1: 255/659; Pilot 2: 239/527). Inpatient SDM + CHW-navigation shows promise to improve LCS rates among underserved patients who smoke, but feasibility is limited by recent diagnostic chest CT among inpatients. Implementing CHW-navigation in other clinical settings may facilitate LCS for underserved patients. ClinicalTrials.gov Identifier: NCT03276806 (8 September 2017); NCT03793894 (4 January 2019).

Utility of Noncancerous Chest CT Features for Predicting Overall Survival and Noncancer Death in Patients With Stage I Lung Cancer Treated With Stereotactic Body Radiotherapy.

BACKGROUND. Noncancerous imaging markers can be readily derived from pre-treatment diagnostic and radiotherapy planning chest CT examinations. OBJECTIVE. The purpose of this article was to explore the ability of noncancerous features on chest CT to predict overall survival (OS) and noncancer-related death in patients with stage I lung cancer treated with stereotactic body radiation therapy (SBRT). METHODS. This retrospective study included 282 patients (168 female, 114 male; median age, 75 years) with stage I lung cancer treated with SBRT between January 2009 and June 2017. Pretreatment chest CT was used to quantify coronary artery calcium (CAC) score, pulmonary artery (PA)-to-aorta ratio, emphysema, and body composition in terms of the cross-sectional area and attenuation of skeletal muscle and subcutaneous adipose tissue at the T5, T8, and T10 vertebral levels. Associations of clinical and imaging features with OS were quantified using a multivariable Cox proportional hazards (PH) model. Penalized multivariable Cox PH models to predict OS were constructed using clinical features only and using both clinical and imaging features. The models' discriminatory ability was assessed by constructing time-varying ROC curves and computing AUC at prespecified times. RESULTS. After a median OS of 60.8 months (95% CI, 55.8-68.0), 148 (52.5%) patients had died, including 83 (56.1%) with noncancer deaths. Higher CAC score (11-399: hazard ratio [HR], 1.83 [95% CI, 1.15-2.91], p = .01; ≥ 400: HR, 1.63 [95% CI, 1.01-2.63], p = .04), higher PA-to-aorta ratio (HR, 1.33 [95% CI, 1.16-1.52], p < .001, per 0.1-unit increase), and lower thoracic skeletal muscle index (HR, 0.88 [95% CI, 0.79-0.98], p = .02, per 10-cm2/m2 increase) were independently associated with shorter OS. Discriminatory ability for 5-year OS was greater for the model including clinical and imaging features than for the model including clinical features only (AUC, 0.75 [95% CI, 0.68-0.83] vs 0.61 [95% CI, 0.53-0.70]; p < .01). The model's most important clinical or imaging feature according to mean standardized regression coefficients was the PA-to-aorta ratio. CONCLUSION. In patients undergoing SBRT for stage I lung cancer, higher CAC score, higher PA-to-aorta ratio, and lower thoracic skeletal muscle index independently predicted worse OS. CLINICAL IMPACT. Noncancerous imaging features on chest CT performed before SBRT improve survival prediction compared with clinical features alone.

Use of Diagnostic CT and Patient Retention in a Lung Cancer Screening Program.

The aims of this study were to assess the rate of subsequent diagnostic chest CT examinations in a lung cancer screening (LCS) program and examine the effect on retention of patients in the program. Patients who underwent LCS CT between June 2011 and August 2018 were included. The occurrence of patients' being subsequently imaged with diagnostic CT versus LCS CT and the effect this had on patients' returning for LCS CT (patient retention) were evaluated. Multivariable logistic regression was used to evaluate variables associated with undergoing diagnostic CT and risk factors associated with loss of patient retention. Of the 5,912 patients who underwent LCS CT, 2,756 underwent subsequent diagnostic or LCS chest CT. Increasing Lung-RADS® score was more likely to lead to subsequent diagnostic chest CT (P < .0001). A total of 1,240 patients underwent at least three chest CT examinations in the time interval. For the 711 patients whose subsequent CT studies were for LCS, 585 (82%) were retained, whereas of the 529 patients who underwent subsequent diagnostic CT, only 208 (39%) were retained (P < .0001). For the 197 subsequent diagnostic CT examinations performed for pulmonary nodule or screening indications, 81 patients (41%) returned for LCS CT, compared with 498 of 612 patients (81%) who underwent subsequent LCS CT (P < .0001). In multivariable analysis, subsequent diagnostic chest CT and increasing Lung-RADS score were associated with loss of retention. A higher Lung-RADS score is a risk factor for subsequent diagnostic chest CT, and this is an independent risk factor for loss from the LCS program.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BackgroundThe combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19.MethodsThis was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1.ResultsBetween July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95–1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77–1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality.ConclusionsWe observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Feasibility of Implementing Thoracic Radiation Therapy for COVID-19 Pneumonia

Purpose/Objective(s)The value of low dose whole thoracic radiation therapy (LD-WTRT) for SARS-CoV-2 (COVID-19) pneumonia is unknown. Should ongoing clinical trials demonstrate LD-WTRT proves effective for COVID-19 pneumonia recovery, widespread rapid implementation will be helpful globally. Our aim was to outline a pragmatic process that could be implemented successfully in a community hospital.Materials/MethodsTo identify appropriate patients admitted to the hospital with COVID-19 pneumonia, we worked with Nursing Informatics to screen all currently admitted COVID+ patients requiring oxygen supplementation. For patients meeting criteria of the PreVent protocol per chart review, radiation oncologists contacted the hospitalist physician for telehealth consultation with the patient to discuss single dose LD-WTRT. After a patient had confirmed interest in treatment, at time of physical exam, we obtained consent and digitally transferred the signed consent form via secure text to avoid contaminated forms. Chest radiographs were used to estimate AP/PA field size and separation at the carina; diagnostic chest CT data was imported into the treatment planning system for field size and MU calculation before patient arrival, without using the department's CT simulator. Inpatient Nursing transported patients for treatment after clinic hours on a route pre-approved by Infection Control. The treating radiation oncologist and one ‘hot’ radiation therapist assisted with patient set-up supine or prone on the linear accelerator couch. After decontamination, the physician and a ‘cold’ therapist confirmed field size and MU calculations to prepare for treatment delivery. Nursing monitored patient O2 saturation and stayed gowned with the ‘hot’ therapist. After patient departure, Radiation Oncology contacted Facilities for decontamination of the vault before treating cancer patients the following day.ResultsFor the first treated patient, telehealth consultation lasted 40 minutes. In-person exam, evaluation and consent took 60 minutes, of which 30 were for the protocol-required consent form. With the diagnostic CT scan, field design and MU calculations took 20 minutes. Patient arrival to departure took 40 minutes. Once the patient was positioned on the couch, localization, MU confirmation and entry and treatment delivery took 16 minutes.ConclusionWe have developed a process to efficiently provide LD-WTRT for patients with COVID pneumonia that minimizes staff exposure, departmental equipment, and room contamination. Should clinical trials indicate that LD-WTRT helps treat COVID pneumonia patients, this process can work in most hospital-based radiation oncology departments to provide LD-WTRT efficiently and safely. Staff and cancer patient vaccination will further lower the risks of implementing LD-WTRT but is not necessary with careful planning and consultation with infection control.

A Subtype of Papillary Thyroid Carcinoma Bone Metastasis With Excellent Response to RAI-Therapy

Introduction: Bone metastases from differentiated thyroid cancer are generally resistant to radioactive iodine (RAI) therapy and are associated with poor prognosis, except for RAI-avid bone metastases with no structural correlate on imaging studies. Case: A 59 y/o woman presented for the evaluation of non-toxic multinodular goiter. Thyroid US showed a 2.7 cm nodule meeting FNAB criteria and no suspicious cervical lymph nodes. Cytology reported a Bethesda IV category with ThyroSeq V3 positive for chromosomal copy number alterations and a high Na+/I− symporter (NIS) expression (27%) with an ~ 60% probability of cancer. The patient underwent left lobectomy with isthmusectomy without neck dissection. Surgical pathology showed a 3.5 cm papillary thyroid carcinoma with extensive angioinvasion (≥4 vessels), negative margins, no ETE, and did not contain a BRAF V600E mutation. Completion thyroidectomy, in anticipation of RAI treatment, showed no additional tumor. Post-operative Tg after 6 weeks was unexpectedly high at 69 ng/mL (negative Tg Ab, TSH 5.7 uIU/ml) which prompted a rhTSH I-123 RAI WBS with SPECT/ CT and a diagnostic chest CT to uncover possible distant metastases. There was RAI uptake in the thyroid bed and right anterolateral 9thrib without a CT correlate (no osteolytic lesion) but with a signal abnormality on MRI. She was categorized as T2NxM1, 8th Edition AJCC Stage IVB, and ATA high risk. She was treated with 148.3 mCi I-131. Unfortunately, 6 months later the Tg was elevated and rising (Tg 38.4 ng/mL, negative Tg Ab, TSH 0.05 uIU/ml). A second diagnostic I-123 WBS with SPECT/ CT showed a new recurrence in the neck but no uptake in the rib lesion on planar images or other distant sites. Because of the unusually high Tg without any RAI-avid metastatic disease, an 18-FDG PET/CT was ordered to search for non-RAI avid disease. This showed disease confined to the neck and increased sclerosis of the rib lesion without increased FDG-uptake consistent with treated disease status post-RAI. There were no other distant hypermetabolic lesions. The left thyroid bed lesion was biopsied and consistent with Bethesda VI cytology and she will soon undergo left central neck dissection with tumor resection. Discussion: RAI-avid bone metastases without structural correlate on high-resolution imaging are a subtype of bone metastases located in the marrow. They do not present as the typical lytic lesions from cortical destruction. They often resolve following RAI treatment, do not cause skeletal-related complications, and do not significantly affect prognosis. The combination of high NIS expression and increased vascularity in the bone marrow (as opposed to the protected microenvironment in the bone cortex) makes them vulnerable to RAI treatment. Recognition of this subset of bone lesions may prevent overtreatment with high doses of RAI treatment and avoid the use of bisphosphonates or external beam radiation.

PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis.

To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed noduleson clinical management in primary abdominal malignancies. This retrospective IRB-approved study included [18F]-FDGPET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDGavidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2mm); their impact on management was alsoinvestigated. A total of 505 nodules (mean 4mm, range 1-23mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influencepatients' management. Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Althoughthis did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients withoutextra-thoracic spread.

Evaluation of the Effect of Sofosbuvir and Daclatasvir in Hospitalised COVID-19 Patients: A Randomized Double-Blind Clinical Trial (DISCOVER)

Background: The combination of sofosbuvir (SOF) and daclatasvir (DCV) has shown preliminary efficacy for patients with COVID-19 in five open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir and daclatasvir to standard care improved clinical endpoints in hospitalized patients with moderate or severe COVID-19. Methods: This was a placebo-controlled, randomized clinical trial in adults with moderate or severe COVID-19 admitted to 19 hospitals in Iran. Patients were randomized to SOF/DCV 400/60mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O 2 saturation Results: Between July and October 2020, 1083 patients were allocated to either the SOF/DCV treatment arm (n=541) or matching placebo (n=542). The primary endpoint was achieved by 358 / 541 (66%) in the SOF/DCV arm and 370 /542 (68%) in controls (relative risk = 0.97, 95% CI = 0.89-1.05). The in-hospital death rates were 58/541 (11%) in the SOF/DCV group versus 53/542 (10%) in the placebo group (relative risk = 1.1, 95% CI = 0.77 to 1.56). Conclusions: We observed no significant effect of SOF/DCV versus placebo on the rate of hospital discharge or survival in hospitalized COVID-19 patients. However, the patient population was generally severe cases that may have been too advanced for antiviral drugs to be effective. Trial Registration: Iran Registry of Clinical Trials under IRCT20200624047908N1 available at https://www.irct.ir/trial/49198.Funding: This trial was sponsored by Abadan University of Medical Sciences and funded by the International Treatment Preparedness Coalition (grant number ITPC-2020)Declaration of Interests: S.Merat has received travel grants from and is a stockholder of Fanavaran Rojan Mohaghegh Daru Co. ANB and HNB are stockholders of Fanavaran Rojan Mohaghegh Daru Co. All other authors: none to declare.Ethics Approval Statement: The study protocol has been approved by the Abadan Faculty of Medicine Sciences Institutional Review Board and the Iranian Registry of Clinical Trials (IRCT) registry team.

Chest CT for triage during COVID-19 on the emergency department: myth or truth?

PurposeWe aimed to investigate the diagnostic performance of chest CT compared with first RT-PCR results in adult patients suspected of COVID-19 infection in an ED setting. We also constructed a predictive machine learning model based on chest CT and additional data to improve the diagnostic accuracy of chest CT.MethodsThis study’s cohort consisted of 319 patients who underwent chest CT and RT-PCR testing at the ED. Patient characteristics, demographics, symptoms, vital signs, laboratory tests, and chest CT results (CO-RADS) were collected. With first RT-PCR as reference standard, the diagnostic performance of chest CT using the CO-RADS score was assessed. Additionally, a predictive machine learning model was constructed using logistic regression.ResultsChest CT, with first RT-PCR as a reference, had a sensitivity, specificity, PPV, and NPV of 90.2%, 88.2%, 84.5%, and 92.7%, respectively. The prediction model with CO-RADS, ferritin, leucocyte count, CK, days of complaints, and diarrhea as predictors had a sensitivity, specificity, PPV, and NPV of 89.3%, 93.4%, 90.8%, and 92.3%, respectively.ConclusionChest CT, using the CO-RADS scoring system, is a sensitive and specific method that can aid in the diagnosis of COVID-19, especially if RT-PCR tests are scarce during an outbreak. Combining a predictive machine learning model could further improve the accuracy of diagnostic chest CT for COVID-19. Further candidate predictors should be analyzed to improve our model. However, RT-PCR should remain the primary standard of testing as up to 9% of RT-PCR positive patients are not diagnosed by chest CT or our machine learning model.Electronic supplementary materialThe online version of this article (10.1007/s10140-020-01821-1) contains supplementary material, which is available to authorized users.

Standardized Reporting and Management of Suspicious Findings on Chest CT Imaging Is Associated With Improved Lung Cancer Diagnosis in an Observational Study

Follow-up of chest CT scan findings suspicious for lung cancer may be delayed because of inadequate documentation. Standardized reporting and follow-up may reduce time to diagnosis and care for lung cancer. We implemented a reporting system that standardizes tagging of chest CT scan reports by classifying pulmonary findings. The system also automates referral of patients with findings suspicious for lung cancer to a multidisciplinary care team for rapid review and follow-up. The system was designed to reduce the time to diagnosis, particularly for early-stage lung cancer. We evaluated the effectiveness of this system, using a quasi-experimental stepped wedge cluster design, examining 99,148 patients who underwent diagnostic (nonscreening) chest CT imaging from 2015 to 2017 and who had not received a chest CT scan in the preceding 24months. We evaluated the association of the intervention with the incidence of diagnosis and surgical treatment of early-stage (I, II) and late-stage (III, IV) lung cancer within 120days of chest CT imaging. Forty percent of patients received the intervention. Among 2,856 patients (2.9%) who received diagnoses of lung cancer, 28%had early-stage disease. In multivariable analyses, the intervention was associated with 24%greater odds of early-stage diagnosis (OR, 1.24; 95%CI, 1.09-1.41) and no change in the odds of late-stage diagnosis (OR, 1.04; 95%CI, 0.95-1.14). The intervention was not associated with the rate of surgical treatment within 120days. In this large quasi-experimental community-based observational study, implementation of a system that combines standardized tagging of chest CT scan reports with clinical navigation was effective for increasing the diagnosis of early-stage lung cancer.

Organ dose and total effective dose of whole-body CT in multiple myeloma patients

ObjectiveTo evaluate organ dose and total effective dose of whole-body low-dose CT (WBLDCT) performed on different CT-scanner models in patients with multiple myeloma (MM) and to compare it to the effective dose of radiographic skeletal survey and representative diagnostic CTs.Material and methodsWe retrospectively analyzed data from 228 patients (47.4% females, mean age 67.9 ± 10.4 years, mean weight 81.8 ± 22.4 kg) who underwent WBLDCT for the work-up or surveillance of MM. Patients were scanned using one of six multi-detector CT-scanners. Organ doses and total effective doses per scan were calculated using a commercially available dose-management platform (Radimetrics, Bayer Healthcare, Leverkusen, Germany). The median effective dose was compared to radiographic skeletal survey and representative diagnostic CTs.ResultsThe mean effective dose of our WBLDCT-protocol was 4.82 mSv. A significantly higher effective dose was observed in females compared to males (4.95 vs. 4.70 mSv, P = 0.002). Mean organ dose ranged from 3.72 mSv (esophagus) to 13.09 mSv (skeleton). Mean effective dose varied amongst different CT-scanners (range 4.34–8.37 mSv). The median effective dose of WBLDCT was more than twice the dose of a skeletal survey (4.82 vs. 2.04 mSv), 23% higher than a diagnostic contrast-enhanced chest CT (3.9 mSv), 46% lower than a diagnostic contrast-enhanced abdomen/pelvis CT (9.0 mSv), and 45% lower than a lumbar spine CT (8.7 mSv).ConclusionsWBLDCT in MM has a higher effective dose than a radiographic skeletal survey, but a lower effective dose than diagnostic CTs of lumbar spine, abdomen and pelvis. This underlines the broad applicability of WBLDCT in the management of MM patients.

Use of Imaging and Diagnostic Procedures After Low-Dose CT Screening for Lung Cancer

Clinical trials have demonstrated a mortality benefit from lung cancer screening by low-dose CT (LDCT) in current or past tobacco smokers who meet criteria. Potential harms of screening mostly relate to downstream evaluation of abnormal screens. Few data exist on the rates outside of clinical trials of imaging and diagnostic procedures following screening LDCT. We describe rates in the community setting of follow-up imaging and diagnostic procedures after screening LDCT. We used Clinformatics Data Mart national database to identify enrollees age 55 to 80 year who underwent screening LDCT from January 1, 2016, to December 31, 2016. We assessed rates of follow-up imaging (diagnostic chest CT scan, MRI, and PET) and follow-up procedures (bronchoscopy, percutaneous biopsy, thoracotomy, mediastinoscopy, and thoracoscopy) in the 12months following LDCT for lung cancer screening. We also assessed these rates in an age-, sex-, and number of comorbidities-matched population that did not undergo LDCT to estimate rates unrelated to the screening LDCT. We then reported the adjusted rate of follow-up testing as the observed rate in the screening LDCT population minus the rate in the non-LDCT population. Among 11,520 enrollees aged 55 to 80 years who underwent LDCT in 2016, the adjusted rates of follow up 12months after LDCT examinations were low (17.7%for imaging and 3.1%for procedures). Among procedures, the adjusted rates were 2.0%for bronchoscopy, 1.3%for percutaneous biopsy, 0.9%for thoracoscopy, 0.2%for mediastinoscopy, and 0.4%for thoracotomy. Adjusted rates of follow-up procedures were higher in enrollees undergoing an initial screening LDCT (3.3%) than in those after a second screening examination (2.2%). In general, imaging and rates of procedures after screening LDCT was low in this commercially insured population.

A 3-Dimensional CT-Based Analysis of Dosimetric Coverage on the Patterns of Locoregional Recurrence in High-Risk Breast Cancer Patients Treated with Regional Nodal Irradiation

Maximizing dose to regions-at-risk is counterbalanced by efforts to minimize dose to adjacent organs during the treatment planning of locally advanced breast cancer patients. Our goal was to evaluate the association of dosimetric coverage of the target tissues (breast, chest wall, regional nodes) with the incidence of locoregional recurrence (LRR) in breast cancer patients who had been previously treated with RNI. From an institutional database, we identified 57 patients treated for Stage II-III breast cancer between 2000-2014 at single center who developed an isolated LRR following surgery and adjuvant radiation to the breast/chest wall and regional nodes. Eligibility criteria included receipt of conformal RT to the lymph nodes, available DVH data, and radiographic identification of recurrent tumor on imaging scans obtained within 3 months of LRR. Patients with prior distant metastases, recurrence without correlative imaging and prior metastases were excluded. In order to determine the dose coverage in the area of recurrence, we fused the diagnostic chest CT demonstrating recurrence to the original treatment planning CT to create a gross tumor volume-LRR (GTV-LRR). The mean doses to the breast or chest wall, supraclavicular (SCV), Level 1-3 axillary (Ax) and internal mammary nodes (IMN), heart dose (MHD), left anterior descending dose and lung (MLD) were evaluated by DVH. The log-rank test evaluated the association between target coverage and time to the development of LRR. Cox multivariate analysis was adjusted for receptor subtype, receipt of systemic therapy and pathologic stage. A total of 48% of the cohort was comprised of in-breast or chest wall recurrences (BR) and 52% isolated nodal recurrences (NR). Among the NR group, 38% patients received a mean <30 Gy to the GTV-LRR and 62% received mean >30 Gy to the GTV-LRR. The majority of GTV-LRRs in the NR group were in the IMN chain (38%) and axilla (38%), followed by SCV (24%). In the BR group, the association between GTV-LRR and time to LRR was not significant. In contrast, in the NR group, the median time to LRR in patients who received mean<30 Gy GTV-LRR was 7 months , compared to the mean >30 Gy GTV-LRR cohort who failed at a median of 21 months (p=0.03). The mean heart dose in the <30 Gy group was significantly lower, compared to the >30 Gy cohort (p=0.02), indicating that sparing of the heart was prioritized over coverage of target tissues. In this CT-based mapping analysis of LRRs in breast cancer patients previously treated with RNI, the time to development of a nodal recurrence was prolonged by 3-fold when the area had received mean<30 Gy relative to those who had received >30 Gy to the area of eventual recurrence. This study provides proof-of-concept that dosimetric coverage of nodal areas-at-risk should be prioritized in high-risk breast cancer patients receiving radiotherapy.

Abstract 3317: Development of a lung nodule cohort with integrated clinical, molecular and imaging biomarkers

Abstract Background: We are facing an epidemic of indeterminate pulmonary nodules (IPN). Current diagnostic strategies lack accuracy such that the management of IPNs 6-30 mm leads to an unacceptable rate of invasive biopsies and of missed opportunities for cure. Based on the critical need of evaluating candidate biomarkers across heterogeneous populations, we intended to assemble a large cohort of fully annotated IPNs from five collaborative institutions. Methods: Standard operating procedures (SOPs) were developed to capture subject demographics and assign consistent identifiers across clinical, bio-specimens, and imaging data. REDCap database was created for clinical, imaging and biospecimen data capture. Sample collection, processing, storage and shipping SOPs were created and shared among institutions to assure for consistency and quality accuracy. DICOM files, demographic and clinical data, blood and tissue samples were collected prospectively through IRB approved studies at each institution (VUMC, Nashville VAMC, Moffitt Cancer Center, and UPMC). Imaging studies and specimens were de-identified locally using custom JavaScript program in a secure web browser and assigned as specific identifier. De-identified thin slice, non-contrast chest CT studies were tested for quality control and transmitted to an imaging repository (eXtensible Neuroimaging Repository-XNAT) that can be mined by all collaborators. Results: To date, a cohort of 845 subjects, 507 (60%) males and 338 (40%) females, with lung nodules was assembled. 36 % are current smokers, 56 % former smokers and 8% never smokers, with an average of 46 pack year smoking history. Clinical data including risk prediction models such as the Mayo and PLCO m2012 are reported. Pathological confirmation of nodules is available for 322 benign and 444 malignant nodules. The cohort 283 lung adenocarcinomas, 71 squamous cell carcinomas, 53 small cell carcinoma, 17 non-small cell lung cancer, 9 carcinoid, and 79 subjects considered benign based on CT follow without growth. Serum, plasma and peripheral blood monocyte related DNA is available on all. All diagnostic chest CT are available in our thoracic imaging repository (XNAT) in a de-identified format. Conclusions: We assembled a unique cohort of incidental and screening detected lung nodules prospectively enrolled at four institutions for which full clinical data capture, chest CT DICOM files and blood specimens were collected. This repository allows the derivation and independent validation of candidate molecular and imaging biomarkers for the management of IPNs. This work is supported by UO1 152662, UO1CA186145 and UO1CA196405 Citation Format: Sanja Antic, Travis Osterman, Aneri Balar, Dhairya Lakhani, Rina Nguyen, Sara Block, Kimberly Fileds, Brandon Winston, Anel Muterspaugh, Yuankai Huo, Riqiang Gao, Joseph Leader, David Wilson, Viswam Nair, Robert Gillies, Matthew Schabath, Chirayu Shah, Bennett Landman, Pierre Massion. Development of a lung nodule cohort with integrated clinical, molecular and imaging biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3317.

Calculation of lung mean dose and quantification of error for 90 Y-microsphere radioembolization using 99m Tc-MAA SPECT/CT and diagnostic chest CT.

Current treatment planning for 90 Y radioembolization estimates lung mean dose (LMD) by measuring the lung shunt fraction (LSF) from 99m Tc-macroaggregated albumin (MAA) planar imaging and assuming a 1-kg lung mass. This methodology, however, overestimates LSF and LMD and could therefore unnecessarily limit the dose to target volume(s). We propose an improved LMD calculation that derives LSF from 99m Tc-MAA SPECT/CT and the patient-specific lung mass from diagnostic chest CT. Furthermore, we investigated the errors in lung mass, LSF, and LMD arising from contour variability in patient data in order to estimate the precision of our proposed methodology. Our proposed LMD (LMDnew ) calculation consisted of the following steps: (a) estimate liver counts from the MAA SPECT/CT liver contour; (b) estimate total lung counts by multiplying density (counts/g) from the MAA SPECT/CT left-lung contour by the total lung mass (g) from the diagnostic CT lung contours; (c) compute LSFnew from liver and lung counts; (d) calculate LMDnew using LSFnew and the total lung mass from the diagnostic CT (Mnew ). LMDnew , LSFnew , and Mnew estimates were compared to standard model values (LMDclin , LSFclin , and 1kg, respectively) in 52 consecutive patients with hepatocellular carcinoma who underwent radioembolization using 90 Y glass microspheres. The precision of our methodology was quantified by varying lung and liver contours in the same patient population and calculating the resulting relative errors in the liver count, lung count, and lung mass measurements. The median Mnew was 839g (range, 550-1178g) for men and 731g (range, 548-869g) for women. The median LSFnew was 0.02 (range, 0.01-0.11), while the median LMDnew was 4.9Gy (range, 0.3-25.5Gy). Mnew , LSFnew , and LMDnew were significantly lower than Mclin , LSFclin , and LMDclin , with respective relative mean (±SD) differences of -20% (±16%) for Mnew , -63% (±15%) for LSFnew , and -53% (±23%) for LMDnew . The estimated 1-sigma uncertainties in Mnew , LSFnew , and LMDnew were 9%, 10%, and 13%, respectively. We derived a method to calculate lung mass and LSF using routinely available diagnostic chest CT and 99m Tc-MAA SPECT/CT. More importantly, we systematically quantified the errors in our measurements to establish the precision of the estimated lung dose (13%). The proposed methodology provides a more accurate LMD and an estimate of its precision, which will improve treatment and retreatment planning for 90 Y radioembolizations.

Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trial

SummaryBackgroundWhole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC.MethodsThe Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete.FindingsBetween Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37–63) for WB-MRI and 54% (41–67) for standard pathways, a difference of 4% (−7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88–96]) and standard pathways (95% [91–98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12–14]) than for the standard pathway (19 days [17–21]); a 6-day (4–8) difference. The number of tests required was similar WB-MRI (one [1–1]) and standard pathways (one [1–2]). Mean per-patient costs were £317 (273–361) for WBI-MRI and £620 (574–666) for standard pathways.InterpretationWB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs.FundingUK National Institute for Health Research.

03:18 PM Abstract No. 327 A novel lung dose calculation methodology for Y90-radioembolization using diagnostic chest-CT and Tc99m-MAA SPECT/CT

03:18 PM Abstract No. 327 A novel lung dose calculation methodology for Y90-radioembolization using diagnostic chest-CT and Tc99m-MAA SPECT/CT

Chest CT findings among adult survivors of childhood and young adult cancer with a history of chest radiation.

103 Background: While survivors of childhood and young adult cancer with a history of radiation therapy (RT) to the chest are known to be at increased risk for lung cancer, whether a CT-based lung cancer screening program is appropriate for this population is unknown. We sought to describe CT findings in a clinic-based population of childhood and young adult cancer survivors. Methods: We performed a detailed review of all diagnostic chest CT scans performed among patients seen in the Adult Long-Term Follow-Up Program at Memorial Sloan Kettering between August 2005 and May 2016. Included survivors were at least 5 years from diagnosis and had a history of RT to the mediastinum, mantle, axilla, lung, thoracic spine, or total body irradiation fields. Results were reviewed by at least two authors (ET, DB, or AK) and discrepancies were resolved by consultation with a pulmonologist (RK). Results: We identified 620 survivors with a history of chest field RT who were at least 5 years from diagnosis. The population was 48% male, with a median age at diagnosis of 17.2 years. Approximately half were survivors of Hodgkin Lymphoma (N=306; 49.5%) and almost one-third had undergone hematopoietic cell transplant (N=188; 31%); other diagnoses included non-Hodgkin Lymphoma and sarcoma. The most frequently cited RT field was mantle (N=219; 36%), followed by total body irradiation (N=142; 24%) and whole lung (N=110;18%). Among 351 survivors with at least one chest CT, 206 (59%) had at least one pulmonary nodule, 174 (50%) had fibrosis, and 132 (38%) had a ground glass opacity. Among those with a pulmonary nodule, the large majority (91% of those with a nodule) were followed expectantly or underwent repeat imaging; these patients were spared biopsy or resection. Among 18 patients who underwent biopsy, wedge resection, fine needle aspiration, or bronchoscopy, 4 were diagnosed with lung adenocarcinoma, 3 with metastatic sarcoma, and one with marginal zone lymphoma (MALT). Conclusions: Benign pulmonary nodules among adults with a history of RT for childhood or young adult cancer are common. Any strategy for lung cancer screening in this population will need to account for a high likelihood of benign findings on chest CT.

A Study of the Feasibility of FDG-PET/CT to Systematically Detect and Quantify Differential Metabolic Effects of Chronic Tobacco Use in Organs of the Whole Body—A Prospective Pilot Study

The aim of this study was to assess the feasibility of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) to systematically detect and quantify differential effects of chronic tobacco use in organs of the whole body. Twenty healthy male subjects (10 nonsmokers and 10 chronic heavy smokers) were enrolled. Subjects underwent whole-body FDG-PET/CT, diagnostic unenhanced chest CT, mini-mental state examination, urine testing for oxidative stress, and serum testing. The organs of interest (thyroid, skin, skeletal muscle, aorta, heart, lung, adipose tissue, liver, spleen, brain, lumbar spinal bone marrow, and testis) were analyzed on FDG-PET/CT images to determine their metabolic activities using standardized uptake value (SUV) or metabolic volumetric product (MVP). Measurements were compared between subject groups using two-sample t tests or Wilcoxon rank-sum tests as determined by tests for normality. Correlational analyses were also performed. FDG-PET/CT revealed significantly decreased metabolic activity of lumbar spinal bone marrow (MVPmean: 29.8 ± 9.7 cc vs 40.8 ± 11.6 cc, P = 0.03) and liver (SUVmean: 1.8 ± 0.2 vs 2.0 ± 0.2, P = 0.049) and increased metabolic activity of visceral adipose tissue (SUVmean: 0.35 ± 0.10 vs 0.26 ± 0.06, P = 0.02) in chronic smokers compared to nonsmokers. Normalized visceral adipose tissue volume was also significantly decreased (P = 0.04) in chronic smokers. There were no statistically significant differences in the metabolic activity of other assessed organs. Subclinical organ effects of chronic tobacco use are detectable and quantifiable on FDG-PET/CT. FDG-PET/CT may, therefore, play a major role in the study of systemic toxic effects of tobacco use in organs of the whole body for clinical or research purposes.