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The aims of the present study were (a) to evaluate mediastinal staging in patients with lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) using a coincidence gamma camera (hybrid PET) in comparison with dedicated positron emission tomography (PET) and computed tomography (CT), and (b) to assess the feasibility to determine standardized uptake values (SUV) with hybrid PET. Forty patients were included in the study. Hybrid PET was performed without and with attenuation correction. Data were rebinned with single-slice (SSRB) or Fourier rebinning (FORE). The SUVs of primary tumors were calculated with hybrid PET and compared with SUVs determined by dedicated PET. Diagnostic accuracy for hybrid with or without attenuation correction was 80 or 74% compared with 82% for dedicated PET, and 63% for CT. Attenuation-corrected hybrid PET revealed a higher specificity than CT (83 vs 52%; p<0.05). The SUVs of primary tumors were similar to those of hybrid PET and dedicated PET with a mean relative difference of 20.8+/-16.4%. The FORE improved the agreement of SUVs with a mean relative difference of 13.8+/-9.9 vs 36.0+/-17.9% for SSRB ( p<0.001). Hybrid PET with attenuation correction is more specific than CT for mediastinal staging in patients with lung cancer ( p<0.05). It reveals similar results in comparison with dedicated PET. Calculation of SUVs with hybrid PET is feasible. [ABSTRACT FROM AUTHOR]

Purpose: With this modeling study, we wanted to estimate the potential gain from incorporating fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning in the radiotherapy treatment planning of CT Stage N2-N3M0 non–small-cell lung cancer (NSCLC) patients. Methods and materials: Twenty-one consecutive patients with clinical CT Stage N2-N3M0 NSCLC were studied. For each patient, two three-dimensional conformal treatment plans were made: one with a CT-based planning target volume (PTV) and one with a PET-CT–based PTV, both to deliver 60 Gy in 30 fractions. From the dose–volume histograms and dose distributions on each plan, the dosimetric factors predicting esophageal and lung toxicity were analyzed and compared. For each patient, the maximal tolerable prescribed radiation dose for the CT PTV vs. PET-CT PTV was calculated according to the constraints for the lung, esophagus, and spinal cord. From these results, the tumor control probability (TCP) was estimated, assuming a clinical dose–response curve with a median toxic dose of 84.5 Gy and a γ50 of 2.0. Dose–response curves were modeled, taking into account geographic misses according to the accuracy of CT and PET in our institutions. Results: The gross tumor volume of the nodes decreased from 13.7 ± 3.8 cm3 on the CT scan to 9.9 ± 4.0 cm3 on the PET-CT scan (p = 0.011). All dose–volume characteristics for the esophagus and lungs decreased in favor of PET-CT. The esophageal V45 (the volume of the esophagus receiving 45 Gy) decreased from 45.2% ± 4.9% to 34.0% ± 5.8% (p = 0.003), esophageal V55 (the volume of the esophagus receiving 55 Gy) from 30.6% ± 3.2% to 21.9% ± 3.8% (p = 0.004), mean esophageal dose from 29.8 ± 2.5 Gy to 23.7 ± 3.1 Gy (p = 0.004), lung V20 (the volume of the lungs minus the PTV receiving 20 Gy) from 24.9% ± 2.3% to 22.3% ± 2.2% (p = 0.012), and mean lung dose from 14.7 ± 1.3 Gy to 13.6 ± 1.3 Gy (p = 0.004). For the same toxicity levels of the lung, esophagus, and spinal cord, the dose could be increased from 56.0 ± 5.4 Gy with CT planning to 71.0 ± 13.7 Gy with PET planning (p = 0.038). The TCP corresponding to these doses was estimated to be 14.2% ± 5.6% for CT and 22.8% ± 7.1% for PET-CT planning (p = 0.026). Adjusting for geographic misses by PET-CT vs. CT planning yielded TCP estimates of 12.5% and 18.3% (p = 0.009) for CT and PET-CT planning, respectively. Conclusion: In this group of clinical CT Stage N2-N3 NSCLC patients, use of FDG-PET scanning information in radiotherapy planning reduced the radiation exposure of the esophagus and lung, and thus allowed significant radiation dose escalation while respecting all relevant normal tissue constraints. This, together with a reduced risk of geographic misses using PET-CT, led to an estimated increase in TCP from 13% to 18%. The results of this modeling study support clinical trials investigating incorporation of FDG-PET information in CT-based radiotherapy planning. [Copyright &y& Elsevier]

Purpose: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non–small-cell lung cancer (NSCLC). Patients and Methods: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V20 <25%, V20 25–37%, and V20 >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment 18F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. Results: A total of 48 Stage I–IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V20 <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V20 35–37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%–40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. Conclusions: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V20 up to 37% is feasible. [Copyright &y& Elsevier]

Purpose: The current tumor, node, metastasis system needs refinement to improve its ability to predict survival of patients with non–small-cell lung cancer (NSCLC) treated with (chemo)radiation. In this study, we investigated the prognostic value of tumor volume and N status, assessed by using fluorodeoxyglucose-positron emission tomography (PET). Patients and Methods: Clinical data from 270 consecutive patients with inoperable NSCLC Stages I–IIIB treated radically with (chemo)radiation were collected retrospectively. Diagnostic imaging was performed using either integrated PET-computed tomography or computed tomography and PET separately. The Kaplan-Meier method, as well as Cox regression, was used to analyze data. Results: Univariate survival analysis showed that number of positive lymph node stations (PLNSs), as well as N stage on PET, was associated significantly with survival. The final multivariate Cox model consisted of number of PLNSs, gross tumor volume (i.e., volume of the primary tumor plus lymph nodes), sex, World Health Organization performance status, and equivalent radiation dose corrected for time; N stage was no longer significant. Conclusions: Number of PLNSs, assessed by means of fluorodeoxyglucose-PET, was a significant factor for survival of patients with inoperable NSCLC treated with (chemo)radiation. Risk stratification for this group of patients should be based on gross tumor volume, number of PLNSs, sex, World Health Organization performance status, and equivalent radiation dose corrected for time. [Copyright &y& Elsevier]

Purpose: To compare source-to-background ratio (SBR)-based PET-CT auto-delineation with pathology in non–small-cell lung cancer (NSCLC) and to investigate whether auto-delineation reduces the interobserver variability compared with manual PET-CT–based gross tumor volume (GTV) delineation. Methods and Materials: Source-to-background ratio–based auto-delineation was compared with macroscopic tumor dimensions to assess its validity in 23 tumors. Thereafter, GTVs were delineated manually on 33 PET-CT scans by five observers for the primary tumor (GTV-1) and the involved lymph nodes (GTV-2). The delineation was repeated after 6 months with the auto-contour provided. This contour was edited by the observers. For comparison, the concordance index (CI) was calculated, defined as the ratio of intersection and the union of two volumes (A∩B)/(A∪B). Results: The maximal tumor diameter of the SBR-based auto-contour correlated strongly with the macroscopic diameter of primary tumors (correlation coefficient = 0.90) and was shown to be accurate for involved lymph nodes (sensitivity 67%, specificity 95%). The median auto-contour–based target volumes were smaller than those defined by manual delineation for GTV-1 (31.8 and 34.6 cm3, respectively; p = 0.001) and GTV-2 (16.3 and 21.8 cm3, respectively; p = 0.02). The auto-contour–based method showed higher CIs than the manual method for GTV-1 (0.74 and 0.70 cm3, respectively; p < 0.001) and GTV-2 (0.60 and 0.51 cm3, respectively; p = 0.11). Conclusion: Source-to-background ratio–based auto-delineation showed a good correlation with pathology, decreased the delineated volumes of the GTVs, and reduced the interobserver variability. Auto-contouring may further improve the quality of target delineation in NSCLC patients. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to investigate the relation between the standardised uptake value (SUV) on 18F-fluoro-2-deoxy-glucose-positron emission tomography scan and hypoxia related markers (HIF-1α and CAIX), a proliferation-related marker (Ki-67) and glucose transporters (GLUT-1 and GLUT-3) in non-small cell lung cancer (NSCLC). One hundred and two patients, scheduled for complete resection, received a PET scan in Leuven or Maastricht/Aachen. The maximal SUV (SUVmax) was correlated with survival and immunohistochemical staining patterns. The actuarial survival was worse for patients showing a high SUVmax, the best discriminative value being 8.0 (Leuven, p =0.032) and 11.0 (Maastricht, p =0.007). Tumours with a high SUVmax expressed in a higher proportion HIF-1α (63.1% versus 37.9%, p =0.024) and GLUT-1 (82.9% versus 62.5%, p =0.025), than tumours with a low SUVmax. No significant difference was found in the expression of CAIX, Ki-67 and GLUT-3. This study supports preclinical data that hypoxia is associated with a higher uptake of FDG. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the patterns of recurrence when elective node irradiation was omitted in patients with limited disease small cell lung cancer (LD-SCLC). Methods: A prospective phase II study was undertaken in 27 patients with LD-SCLC without detectable distant metastases on CT scan. Chest radiotherapy to a dose of 45Gy in 30 fractions in 3 weeks (1.5Gy BID with 6–8h interval) was delivered concurrently with carboplatin and etoposide chemotherapy. Chest radiation started after a mean time of 17.7 days±9.7 days (SD) (range: 0–33 days) after the beginning of chemotherapy. Only the primary tumour and the positive nodal areas on the pre-treatment CT scan were irradiated. A total of five chemotherapy cycles were administered, followed by prophylactic cranial irradiation (PCI) in patients without disease progression. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. Results: After a median time of 18 months post-radiotherapy, 7 patients (26%, 95% CI 19.5–42.5%) developed a local recurrence. Three patients (crude rate 11%, 95% CI 2.4–29%), developed an isolated nodal failure, all of them in the ipsilateral supraclavicular fossa. The median actuarial overall survival was 21 months (95% CI 15.3–26.7), and the median actuarial progression free survival was 16 months (95% CI 6.5–25.5). Eight patients developed an acute, reversible grade 3 (CTC 3.0) radiation oesophagitis (30%, 95% CI 14–50%). Conclusions: Because of the small sample size, no definitive conclusions can be drawn. However, the omission of elective nodal irradiation on the basis of CT scans in patients with LD-SCLC resulted in a higher than expected rate of isolated nodal failures in the ipsilateral supraclavicular fossa. The incidence of acute, reversible oesophagitis was in the same range as reported with elective nodal fields. The safety of selective nodal irradiation in NSCLC should not be extrapolated to patients with LD-SCLC until more data are available. In the mean time, elective nodal irradiation should only be omitted in clinical trials. [Copyright &y& Elsevier]

Summary: Although lung cancer is a highly prevalent type of cancer, the effects of an inpatient multidisciplinary rehabilitation program on pulmonary function and exercise capacity have never been studied in these patients. Pulmonary function, 6-min walking distance and peak exercise capacity of 10 patients with a severely impaired pulmonary function following treatment of lung cancer were assessed in this pilot study before and after an 8-week inpatient multidisciplinary rehabilitation program. At baseline, patients had a restrictive pulmonary function and an apparent exercise intolerance (median 6-min walking distance: 63.6% predicted; median peak cycling load: 58.5% predicted). Despite the lack of change in median pulmonary function [FEV1: −0.01L, p =0.5469], functional exercise capacity [145m; 43.2% of the initial values, p =0.0020] and peak exercise capacity [26W; 34.4% of the initial values, p =0.0078] improved significantly compared to baseline. Future trials have to corroborate the present findings. Nevertheless, patients with lung cancer have a clear indication to start a comprehensive rehabilitation program following intensive treatment of their disease. In fact, based on the results of the present pilot study it appears that these patients are good candidates for pulmonary rehabilitation programs. [Copyright &y& Elsevier]

Purpose: To evaluate the patterns of recurrence when selective mediastinal node irradiation based on FDG-PET scan data is used in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: A prospective Phase I/II study was undertaken on 44 patients with NSCLC without detectable distant metastases on CT and FDG-PET scan, delivering either 61.2 Gy in 34 fractions over 23 days or 64.8 Gy in 36 fractions over 24 days (1.8 Gy b.i.d. with 8-h interval). Only the primary tumor and the positive mediastinal areas on the pretreatment FDG-PET scan were irradiated. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. Results: The CT and FDG-PET stage distribution was as follows: Stage I: 8 patients (18%) and 13 patients (29%); Stage II: 6 patients (14%) and 10 patients (23%); Stage IIIA: 15 patients (34%) and 7 patients (16%); Stage IIIB: 15 patients (34%) and 14 patients (32%), respectively. After a median follow-up time of 16 months (95% confidence interval [CI], 11-21 months) postradiotherapy, 11 patients (25%) developed a local recurrence. Only 1 patient (crude rate, 2.3%; upper bound of 95% CI, 10.3%), with a Stage II tumor on both CT and PET, developed an isolated nodal failure. The median actuarial overall survival was 21 months (95% CI, 14-28 months), and the median actuarial progression-free survival was 18 months (95% CI, 12-24 months). Conclusions: Selective mediastinal node irradiation based on FDG-PET scan data in patients with NSCLC results in low isolated nodal failure rates. In the Phase I component of this trial, radiation dose escalation up to 64.8 Gy in 36 fractions over 24 days is feasible. [ABSTRACT FROM AUTHOR]