Fast and accurate staging is essential for choosing treatment for non–small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET–CT) on preoperative staging of NSCLC. We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET–CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause within 1 year after randomization. From January 2002 through February 2007, we randomly assigned 98 patients to the PET–CT group and 91 to the conventional-staging group. Mediastinoscopy was performed in 94% of the patients. After PET–CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. Sixty patients in the PET–CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET–CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups. The use of PET–CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. (ClinicalTrials.gov number, NCT00867412.)

Background The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial. Methods 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice. Results Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs 24, p<0.001), and more were low stage (48 vs 21 stage I–IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA–IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428). Conclusion CT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

Rationale: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. Objectives: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. Methods: A total of 4,104 participants aged 50–70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). Measurements and Main Results: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66–1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82–1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. Conclusions: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with ¹¹¹In-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with ¹²³I-metaiodobenzylguanidine (MIBG), and ¹⁸F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, ¹²³I-MIBG scintigraphy, and ¹⁸F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, ¹²³I-MIBG scintigraphy, and ¹⁸F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were ¹⁸F-FDG PET-positive, of which 3 were also ¹²³I-MIBG scintigraphy–positive, giving a combined overall sensitivity of 96%. SRS also exceeded ¹²³I-MIBG scintigraphy and ¹⁸F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. ¹²³I-MIBG scintigraphy was superior to ¹⁸F-FDG PET for ileal neuroendocrine tumors, and ¹⁸F-FDG PET was superior to ¹²³I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of ¹⁸F-FDG PET (92%) exceeded that of both SRS (69%) and ¹²³I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of ¹²³I-MIBG scintigraphy and ¹⁸F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, ¹⁸F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, ¹⁸F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.

Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up and treatment planning of neuroendocrine tumor (NET) patients. Positron emission tomography (PET) based tracers using ⁶⁸Ga as the radioisotope have in most centers replaced single-photon emission tomography (SPECT) based tracers as the gold standard. ⁶⁴Cu-DOTATATE is a new PET tracer that has been shown to be far superior compared to the SPECT tracer ¹¹¹In-DTPA-octreotide. Due to advantages of ⁶⁴Cu compared to ⁶⁸Ga, we hypothesize that the tracer could have a higher sensitivity than ⁶⁸Ga-based tracers. To test this hypothesis, we compared on a head-to-head basis the diagnostic performance of ⁶⁴Cu-DOTATATE with that of ⁶⁸Ga -DOTATOC in NET patients. Methods: Fifty-nine NET patients were scanned both with ⁶⁴Cu-DOTATATE and ⁶⁸Ga-DOTATOC PET and computed tomography (CT) and compared on a head-to-head basis. Discordant lesions were verified during at least 30 months of follow-up. Results: A total of 701 lesions were concordantly detected on both ⁶⁴Cu-DOTATATE and ⁶⁸Ga-DOTATOC PET/CT scans while an additional 68 lesions were found by only one of the scans. ⁶⁴Cu-DOTATATE showed 42 lesions not found on ⁶⁸Ga-DOTATOC of which 33 were found to be true positive on follow up. ⁶⁸Ga-DOTATOC showed 26 lesions not found on ⁶⁴Cu-DOTATATE of which 7 were found to be true positive on follow up. False positives were mainly lymph node lesions. Accordingly, 83% of the additional true lesions only found on one of the scans were found by ⁶⁴Cu-DOTATATE. On a patient-basis additional true lesions were found by ⁶⁴Cu-DOTATATE and ⁶⁸Ga-DOTATOC in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusion: ⁶⁴Cu-DOTATATE possesses advantages in the detection of lesions in NET patients compared to ⁶⁸Ga-DOTATOC. Although patient based sensitivity was the same for ⁶⁴Cu-DOTATATE and ⁶⁸Ga-DOTATOC in this cohort, significant more lesions were detected by ⁶⁴Cu-DOTATATE. Furthermore, the shelf life of more than 24 hours and the scan window of at least 3 hours make ⁶⁴Cu-DOTATATE very favorable and easy to use in the clinical setting.