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D.F. Yankelevitz
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MINI 36 - Imaging and Diagnostic Workup (ID 163)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
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MINI36.11 - Pre-Operative Fine Needle Aspiration (FNA) for Diagnosis of Suspected Early Stage Lung Cancer Reduces Non-Malignant Resection Rate (ID 2124)
19:30 - 19:35 | Author(s): D.F. Yankelevitz
- Abstract
- Presentation
Background:
Rates of resection of non-malignant lung nodules suspected pre-operatively to be lung cancer vary widely and are reported to be as high as 40%. Commonly used modalities in the pre-operative workup of new lung nodules suspicious for lung cancer include positron emission tomography (PET), bronchoscopy, and computed tomography (CT)-guided fine needle aspiration (FNA). We evaluated the non-malignant resection rate (NMRR) and the frequency of benign resections among patients with pre-operative FNA in our lung cancer center.
Methods:
The study population was identified using databases of the Mount Sinai Departments of Thoracic Surgery and Radiology. Eligible patients included those with a CT-guided FNA and/or surgical resection performed during the 12-month period between July 2013 – July 2014 for known or suspected first primary early stage lung cancer presenting with a lung nodule or mass. Cases were included if patients were >18 years of age with no history of cancer treated within 5 years. Patient data were abstracted from the electronic medical records.
Results:
A total of 283 nodules from 264 patients met inclusion criteria. Of these, FNA was performed in 217 (77%) of the 264 patients, with 131 results (60%) categorized as malignant. Similarly, 228 nodules (81%) were PET imaged, and 141 (62%) of these were positive (Standard Uptake Value >2). Sensitivity and specificity of FNA and PET for diagnosis are reported in Table 1. Post-FNA pneumothorax requiring a chest tube occurred in 11/193 FNAs performed at Mount Sinai (6%). Of 208 surgically resected nodules, 27 cases (13.0%) had a non-malignant diagnosis on pathologic examination. The non-malignant resection rate (NMRR) ranged from 0% to 39% by different surgeons and did not correlate with surgical case volume. Among the 142 resections preceded by FNA, 11 (7.7%) were found to have non-malignant pathology. In contrast, among the remaining 66 resections without a pre-operative FNA, 16 (24.2%) were benign (OR 3.81, 95%CI 1.52-9.69; p = 0.001). Figure 1
Conclusion:
In this single center retrospective analysis, the overall NMRR was lower than in previously published reports. Furthermore, the NMRR was significantly lower in thoracic operations preceded by a CT-guided FNA compared with those without a pre-operative FNA. Diagnostic accuracy of FNA in this cohort of patients at moderate to high risk for lung cancer is higher than that of PET, with an acceptably low complication rate. These findings suggest that pre-operative diagnostic confirmation by FNA results in a low rate of non-malignant resection.
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MS 24 - CT Screening: Minimize Harm/Cost and Risk Assessment (ID 42)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:D. Midthun, J.H. Pedersen
- Coordinates: 9/09/2015, 14:15 - 15:45, Four Seasons Ballroom F3+F4
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MS24.01 - Definition of Positive Cases and False Positives (ID 1954)
14:20 - 14:40 | Author(s): D.F. Yankelevitz
- Abstract
- Presentation
Abstract:
With the ever increasing acceptance of CT screening the need to now minimize harms becomes even greater. One of the harms which occurs with the greatest frequency are “false positives” as they can lead to unnecessary additional work up, sometimes invasive, added cost, and cause anxiety for the person being screened. The term “false positive” is somewhat confusing and is defined differently by different groups. In the computer aided diagnosis domain, it refers to a finding that does not represent a nodule and is mistakenly labelled by the computer to represent nodule. Most frequently this is a blood vessel. Thus, positive results are nodules (often described as actionable based on a size criteria) and false positives are findings not representing nodules. In the clinical domain, when interpreting a CT scan, a positive finding is something that meets a specified definition to be considered a positive result. A positive finding is not something that is inherent to the image but requires certain criteria to be met. Thus, a nodule by itself is not necessarily a positive finding, but must meet certain criteria to be considered positive. Typically it is a non-calcified nodule of a specific size. Thus, in the National Lung Screening Trial the cutoff was at 4 mm, while in I-ELCAP it was at 5 mm for non-calcified nodules. Given a positive result, the confusion now occurs in terms of whether the nodule actually turns out to be a cancer or not. Some prefer to call these cases “false positive” even though they are truly nodules and positive in the sense that they meet the definition of positive based on the CT criteria. Others merely refer to the rate at which positive results occur considering them all positive regardless of their final disposition with the view that imaging does not determine malignancy. Regardless of the linguistics and their potential for causing some confusion, the main concern is to limit the excess amount of work up on those cases which are not cancer. This can be accomplished primarily in two ways. First, to be certain that the population being screened is at high risk for cancer, and secondly, to identify those criteria most associated with cancer and use that in the definition of a positive result. By far, the most dominant of those criteria is size defined either volumetrically or by diameter. An important consideration when defining size cutoffs for positive results, is that the frequency of nodules decreases with increasing size, and the frequency of cancer increases with increasing size. Also, with increasing size of the cancer, the chance for cure decreases. The extent to which all this occurs is not fully known and has many additional considerations. As a start however, and especially in the era of increased scanner resolution, the frequency of positive results would approach 100% if the size criteria is made small enough and the overwhelming majority would be benign. One approach to determining an optimal size criteria is to perform a sensitivity analysis on a screening population balancing the positive rate against what might be considered an acceptable “miss” rate. Using the I-ELCAP database, the frequency of positive results in the baseline round using the 5 mm size cutoff for positive result (any parenchymal, solid or part-solid, noncalcified nodule ≥5.0 mm) was 16% (3396/21 136). When alternative threshold values of 6.0, 7.0, 8.0 and 9.0 mm were used, the frequencies of positive results were 10.2% (95% CI, 9.8% to 10.6%), 7.1% (CI, 6.7% to 7.4%), 5.1% (CI, 4.8% to 5.4%), and 4.0% (CI, 3.7% to 4.2%), respectively. Use of these alternative definitions would have reduced the work-up by 36%, 56%, 68%, and 75%, respectively. Concomitantly, lung cancer diagnostics would have been delayed by at most 9 months for 0%, 5.0% (CI, 1.1% to 9.0%), 5.9% (CI, 1.7 to 10.1%), and 6.7% (CI, 2.2% to 11.2%) of the cases of cancer, respectively. This type of analysis was also performed on the NLST data which using their 4 mm size cutoff had reported a 26.6% positive rate on baseline. The frequency of positive results using the definition of a positive result of any parenchymal, solid or part-solid, noncalcified nodule of 5.0 mm or larger was 15.8%. Using alternative thresholds of 6.0, 7.0, 8.0, and 9.0 mm, the frequencies of positive results were 10.5% (2700 of 25 813, 7.2% , 5.3% , and 4.1% , respectively, and the corresponding proportional reduction in additional CT scans would have been 33.8% , 54.7% , 66.6% , and 73.8% , respectively. Concomitantly, the proportion of lung cancer diagnoses determined within the first 12 months would be delayed up to 9 months for 0.9% (two of 232), 2.6% (six of 232), 6.0% (14 of 232), and 9.9% (23 of 232) of the patients, respectively. The use of the 6 mm size threshold has now gained widespread acceptance in the context of screening having been endorsed by the NCCN, Lung-Rads and I-ELCAP. Nevertheless, it must still be recognized that the tradeoff is the delay in diagnosis of some small cancers for an additional nine months when the next annual screen would occur. While these cancers are unlikely to substantially change in size, the potential for progression is still present and this is the main consideration in balancing against the decrease in positive rate. While size does remain the dominant feature in defining a positive result in this high risk population, there are other approaches that consider additional features of the nodules that also have prognostic significance and may be useful in defining positive results.
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ORAL 35 - Surgical Approaches in Localized Lung Cancer (ID 155)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:M. de Perrot, J. Mitchell
- Coordinates: 9/09/2015, 16:45 - 18:15, 601+603
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ORAL35.05 - The Role of Surgical Mediastinal Resection in CT Screen-Detected Lung Cancer Patients (ID 960)
17:28 - 17:39 | Author(s): D.F. Yankelevitz
- Abstract
- Presentation
Background:
Comparison of long-term survival of patients with clinical Stage I non-small-cell lung cancer (NSCLC) with and without mediastinal lymph node resection (MLNR) in the International Early Lung Cancer Action Program, a large prospective cohort in a low-dose CT screening program.
Methods:
All instances of thoracic surgery for first solitary primary non-small-cell lung cancer prompted by low-dose CT screening, performed under an IRB approved common protocol at each of the participating institutions since 1992 to 2014, are included. Follow-up time was calculated from diagnosis to death from lung cancer, last contact, or December 31, 2014, whichever came first. Univariate logistic regression analysis of the demographic, CT, and surgical findings for those with and without MLNR was performed. Kaplan-Meier (K-M) survival rates and Cox regression analysis was performed using all significant univariate variables.
Results:
The 10-year Kaplan-Meier (K-M) NSCLC-specific survival rate for the 225 patients manifesting as a subsolid nodule was 100%, regardless of whether they had MLNR (N = 169) or not (N = 56). For the 373 NSCLC patients manifesting as a solid nodule, for those who had MLNR (N = 285) and those who did not (N = 88), the K-M NSCLC-survival rate was not significantly different (86 % vs. 93%, P = 0.23). The rate was 95% vs. 96% (P = 0.86) for those whose pathologic tumor diameter was <= 10 mm; 83% vs. 94% (P = 0.19) for 11-20 mm, and 79% vs. 86% (P = 0.67) for 21-20 mm. Cox regression analysis comparing MLNR with no MLNR showed that survival rates were not significantly different (P = 0.33), but significantly survival decreased when the tumor diameter was above 20 mm (HR= 5.1, 95% CI: 1.6-15.7).
Conclusion:
Lymph node evaluation is not necessary for resection of subsolid nodules in patients with screen-detected lung cancer.
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P3.06 - Poster Session/ Screening and Early Detection (ID 220)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.06-006 - Extent of Progression for Small Cancers in a Screening Program Even with Proper Follow-Up (ID 3096)
09:30 - 09:30 | Author(s): D.F. Yankelevitz
- Abstract
Background:
Current guidelines for repeat CT imaging of small nodules detected during screening are a function of the size and consistency of the nodules and the round it was detected. They attempt to balance the frequency with which a change would genuinely occur (i.e. the frequency with which a nodule of a given size is a cancer) with the ability to actually measure the change should it have occurred. Recently the American College of Radiology has established a new set of guidelines for this purpose called LungRads. This study analyzes the change in nodule volumes and doubling times for small nodules if the LungRads guidelines are followed.
Methods:
The LungRads protocol focuses on providing categories for nodules based on their degree of suspiciousness and provides suggestions for follow-up. They also provide criteria so as to determine when growth is genuine —that is, the change in size is beyond what could have occurred solely as a result of measurement error. Genuine growth defined as increase in diameter of >1.5 mm. For purposes of estimating change in nodule volume and doubling times associated with them, we used the time intervals in LungRads for follow-up and derived the doubling times necessary for a nodule to reach the definitional growth threshold. We assumed a spherical model for the nodules and used a simple exponential growth rate. We focused on solid nodules where the range of growth rates is known to be large and they are most accurately measured.
Results:
For LungRads Category 2, where 6 month follow up CT is recommended, in order for a 4 mm nodule to grow sufficiently so as to pass the size threshold where change could be detected, it would need to have a doubling time faster than 129 days, anything slower would not achieve the necessary size change and it would only then be rescanned 6 months later at an annual repeat scan and it would then potentially reach a size of 8.0 mm. For category 4A, LungRads recommends repeat scanning in 3 months. According to the protocol, a 6 mm nodule would need a doubling time of 92 days for detection otherwise at one year it will reach a size of 15.1 mm.
Conclusion:
The change threshold for growth and time intervals between scans can have serious consequences downstream in terms of how large a tumor might become before it can reliably be diagnosed. The ability to better define the threshold for when change has occurred will always be beneficial as it will allow not only the very fast growing tumors to be diagnosed but those with more typical doubling times as well. The LungRads protocol keeps the smallest size category of tumors from growing beyond 15 mm when workup is initiated.
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P3.06-019 - Lung Cancer Deaths in the NLST Attributed to Nonsolid Nodules (ID 3022)
09:30 - 09:30 | Author(s): D.F. Yankelevitz
- Abstract
Background:
There has been increasing awareness of the more indolent course of cancers manifesting in nonsolid nodules, especially among those where the nodule is solitary or dominant. There have been reports of virtually 100% cure rates upon resection and most recently, the recommendation from the ACR in their Lung-RADS screening guidelines is for those nonsolid nodules less than 2 centimeters to be followed by annual screening without additional evaluation. In order to further evaluate the aggressiveness of these types of cancers in the screening setting, we determined how frequently they were the cause of death (COD) within the NLST.
Methods:
We searched the NLST database to identify all participants who had a diagnosis of lung cancer after a positive result on CT screening and whose death was attributed to lung cancer by the NLST endpoint verification process. Among them, 28 participants had at least one nonsolid nodule identified on CT in a screening round. Among these, all cases where the nonsolid nodule could not identified in the study year the cancer was first identified (cancyr) or in the location of the confirmed lung cancer were excluded. All images associated with the remaining 8 cases were downloaded from The Cancer Imaging Archive (TCIA) using the NLST Query Tool and reviewed by three radiologists (DY, DX, MH) to assess nodule consistency and location.
Results:
Among the 8 cases reviewed by the radiologists, only 5 cases had at least one nonsolid nodule. The remaining three cases had no CT evidence of a non-solid nodule (Table 1). Among the 5 cases with nonsolid nodules, 2 cases had another large solid nodule (average diameter of 54.5mm and 15 mm) in the same lobe which was the probable lung cancer that was the cause of death. In another case, the nodule was less than 5 mm in diameter and stable for 3 years, and in another the cause of death was small cell carcinoma which is not known to manifest as a nonsolid cancer. One case manifested on baseline scan with multiple nonsolid and part-solid nodules which all grew on successive annual scans. Table 1. Lung cancer deaths with non-solid nodules in NLST database
*ns-nonsolid; ps-part-solidCase Any NS nodules Size of largest NS Multiple/solitary Stage/Cell-type Comments 128534 Y 29 x 19 Solitary NS Solitary solid IIIA/Squamous cell Large solid nodule (57 x 52) 134088 Y 27 x 20 Multiple NS Multiple solid IV/Small-cell 212718 Y 26 x 26 Multiple NS Multiple PS IV/BAC Cancer reported in all lobes 116279 Y 5 x 4 Solitary NS IV/Carcinoma NOS NS nodule appears stable over 3 years 126576 Y Multiple NS Solitary solid IA/Adeno-mixed Growing solid nodule, 15 mm 117025 N Multiple solid IV/Adeno NOS 208792 N Solitary solid IIIA/Squamous cell 218307 N Solitary solid IIIA/Squamous cell
Conclusion:
It seems unlikely that within the NLST, there were cases of lung cancer specific death that were attributable to cancers manifesting as a solitary or dominant nonsolid nodule. This lends further support that lung cancers manifesting as nonsolid nodules have an indolent course.