Thida Win

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy)

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalised in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.

Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG.

The aim was to assess the relevant distribution of the novel PET tracer 68Ga‐DOTATATE in neuroendocrine tumors (NETs) with combined positron emission tomography / computed tomography (PET/CT) and compare its performance with that of 18F‐FDG PET/CT.

Guidelines on the radical management of patients with lung cancer.

A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.

A Comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in Pulmonary Neuroendocrine Tumors

Our purpose was to compare the performance of 68Ga-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe1,Tyr3-octreotate (DOTATATE), a novel selective somatostatin receptor 2 PET ligand, and 18F-FDG in the detection of pulmonary neuroendocrine tumors using PET/CT, with correlation of uptake and tumor grade on histology. Methods: The imaging findings of the first 18 consecutive patients (8 men and 10 women) with pulmonary neuroendocrine tumors (11 typical carcinoids, 2 atypical carcinoids, 1 large cell neuroendocrine tumor, 1 small cell neuroendocrine carcinoma, 1 non–small cell lung cancer with neuroendocrine differentiation, and 2 cases of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia) who underwent 68Ga-DOTATATE and 18F-FDG PET/CT were reviewed. In all cases, the diagnosis was established on histology. Results: Of 18 patients, 15 had primary tumors (median size, 2.7 cm; range, 0.5–8 cm) and 3 had recurrent tumors. All typical carcinoids showed high uptake of 68Ga-DOTATATE (maximum standardized uptake value [SUVmax] ≥ 8.2), but 4 of 11 showed negative or minimal 18F-FDG uptake (SUVmax = 1.7–2.9). All tumors of higher grade showed high uptake of 18F-FDG (SUVmax ≥ 11.7), but 3 of 5 showed only minimal accumulation of 68Ga-DOTATATE (SUVmax = 2.2–2.8). Neither case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia showed uptake of 68Ga-DOTATATE or 18F-FDG. Typical carcinoids showed significantly higher uptake of 68Ga-DOTATATE and significantly less uptake of 18F-FDG than did tumors of higher grade (P = 0.002 and 0.005). There was no instance of false-positive uptake of 68Ga-DOTATATE, but there were 3 sites of 18F-FDG uptake secondary to inflammation. 68Ga-DOTATATE was superior to 18F-FDG in discriminating endobronchial tumor from distal collapsed lung (P = 0.02). Conclusion: Typical bronchial carcinoids showed higher and more selective uptake of 68Ga-DOTATATE than of 18F-FDG. Atypical carcinoids and higher grades had less 68Ga-DOTATATE avidity but were 18F-FDG–avid.

Tumor heterogeneity and permeability as measured on the CT component of PET/CT predict survival in patients with non-small cell lung cancer.

Purpose: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non–small cell lung cancer (NSCLC). Experimental Design: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan–Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. Results: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0·001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment. Conclusions: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC. Clin Cancer Res; 19(13); 3591–9. ©2013 AACR.

Non-[18F]FDG PET in clinical oncology

PET is an exquisitely sensitive molecular imaging technique using positron-emitting radioisotopes coupled to specific ligands. Many biological targets of great interest can be imaged with these radiolabelled ligands. This review describes the current status of non-18-fluorodeoxyglucose PET tracers that have a potential clinical effect in oncology. With the help of these tracers, knowledge is being acquired on the molecular characterisation of specific tumours, their biological signature, and postinterventional response. The potential role of these imaging probes for tumour detection and monitoring is progressively being recognised by clinical oncologists, biologists, and pharmacologists.

Comparison of shuttle walk with measured peak oxygen consumption in patients with operable lung cancer

Background: The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported. A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting. Methods: 125 consecutive patients with potentially operable lung cancer were prospectively recruited. Each performed same day shuttle walking and treadmill walking tests. Results: Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min. The shuttle walk distance significantly correlated with peak oxygen consumption (r = 0.67, p<0.001). All 55 patients who achieved more than 400 m on the shuttle test had a peak oxygen consumption of at least 15 ml/kg/min. Seventy of 125 patients failed to achieve 400 m on the shuttle walk test; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min. Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min. Conclusion: The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function. However, it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption. Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption. In patients failing to achieve this distance we recommend assessment of peak oxygen consumption, particularly in those unable to walk 250 m, because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption.

Effect of lung cancer surgery on quality of life

Background: Health related quality of life (HRQOL) after surgery is important, although very limited data are available on the QOL after lung cancer surgery. Methods: The effect of surgery on HRQOL was assessed in a prospective study of 110 patients undergoing potentially curative lung cancer surgery at Papworth Hospital, 30% of whom had borderline lung function as judged by forced expiratory volume in 1 second. All patients completed the EORTC QLQ-C30 and LC13 lung cancer module before surgery and again at 1, 3 and 6 months postoperatively. Results: On average, patients had high levels of functioning and low levels of symptoms. Global QOL had deteriorated significantly 1 month after surgery (p = 0.001) but had returned to preoperative levels by 3 months (p = 0.93). Symptoms had worsened significantly at 1 month after surgery but had returned to baseline levels by 6 months. Low values on the preoperative HRQOL scales were not significantly associated with poor surgical outcome. However, patients with low preoperative HRQOL functioning scales and high preoperative symptom scores were more likely to have poor postoperative (6 months) QOL. The only lung function measurement to show a marginally statistically significant association with quality of life at 6 months after surgery was percentage predicted carbon monoxide transfer factor (Tlco). Conclusion: Although surgery had short term negative effects on quality of life, by 6 months HRQOL had returned to preoperative values. Patients with low HRQOL functioning scales, high preoperative symptom scores, and preoperative percentage predicted Tlco may be associated with worse postoperative HRQOL.

The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated?

Idiopathic Pulmonary Fibrosis and Diffuse Parenchymal Lung Disease: Implications from Initial Experience with 18F-FDG PET/CT

The purpose of this study was to evaluate integrated 18F-FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF) and diffuse parenchymal lung disease (DPLD). Methods: Thirty-six consecutive patients (31 men and 5 women; mean age ± SD, 68.7 ± 9.4 y) with IPF (n = 18) or other forms of DPLD (n = 18) were recruited for PET/CT and high-resolution CT (HRCT), acquired on the same instrument. The maximal pulmonary 18F-FDG metabolism was measured as a standardized uptake value (SUVmax). At this site, the predominant lung parenchyma HRCT pattern was defined for each patient: ground-glass or reticulation/honeycombing. Patients underwent a global health assessment and pulmonary function tests. Results: Raised pulmonary 18F-FDG metabolism in 36 of 36 patients was observed. The parenchymal pattern on HRCT at the site of maximal 18F-FDG metabolism was predominantly ground-glass (7/36), reticulation/honeycombing (26/36), and mixed (3/36). The mean SUVmax in patients with ground-glass and mixed patterns was 2.0 ± 0.4, and in reticulation/honeycombing it was 3.0 ± 1.0 (Mann–Whitney U test, P = 0.007). The mean SUVmax in patients with IPF was 2.9 ± 1.1, and in other DPLD it was 2.7 ± 0.9 (Mann–Whitney U test, P = 0.862). The mean mediastinal lymph node SUVmax (2.7 ± 1.3) correlated with pulmonary SUVmax (r = 0.63, P < 0.001). Pulmonary 18F-FDG uptake correlated with the global health score (r = 0.50, P = 0.004), forced vital capacity (r = 0.41, P = 0.014), and transfer factor (r = 0.37, P = 0.042). Conclusion: Increased pulmonary 18F-FDG metabolism in all patients with IPF and other forms of DPLD was observed. Pulmonary 18F-FDG uptake predicts measurements of health and lung physiology in these patients. 18F-FDG metabolism was higher when the site of maximal uptake corresponded to areas of reticulation/honeycomb on HRCT than to those with ground-glass patterns.