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Purpose: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites., Methods and Materials: Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database. We retrospectively compared overall survival (OS) and progression-free survival (PFS) for medically operable or inoperable patients and patients undergoing total or subtotal metastatic ablation. Secondary endpoints were patterns of failure, high-grade treatment toxic effects (Common Terminology Criteria for Adverse Events version 4.0), and freedom from systemic therapy. The threshold dose per fraction considered ablative was 8 Gy., Results: A total of 401 patients with 530 treated oligometastases were included, with a median follow-up of 3 years. Three hundred and two and 99 patients had metachronous and synchronous presentations of oligometastatic disease, respectively. Common histologies included prostate (24%), lung (18%), gastrointestinal (19%), and breast (11%). More than 90% of doses delivered were Biologically Effective Dose [BED 10 ] ≥60 Gy. Cumulative incidence at 5 years of local-only failure was 6%, local and distant 2%, and distant-only 58%. The 3- and 5-year OS [95% confidence intervals {CIs}] were 68% [62-73] and 54% [47-61], and PFS was 20% [15-25] and 14% [10-20]. The 3- and 5-year freedom from systemic therapy [95% CIs] were 40% [34-46] and 31% [24-37], respectively. Seventy-six patients were inoperable and 325 were operable. Operability status was not prognostic for OS (adjusted hazard ratio [HR], 1.0; 95% CI, 0.6-1.7; P = .9) or for PFS (adjusted HR, 1.1; 95% CI, 0.8-1.6; P = .5). Total metastatic ablation was prognostic for OS (adjusted HR, 0.8; 95% CI, 0.4-0.9; P = .032) and for PFS (adjusted HR, 0.6; 95% CI, 0.4-0.8; P = .003)., Conclusions: Medical operability was not prognostic in patients with oligometastatic disease treated with SABR. Total metastatic ablation was associated with superior OS and PFS compared with subtotal metastatic ablation. Our data support ablation of all sites of oligometastases wherever feasible., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS)., Methods: Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1-5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural; B) diffuse (involving more than a segment); and C) peripheral (diffusely surrounding a photopenic region)., Results: Follow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days; interquartile range, 79-93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.6-2.5; p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7; 95% CI, 1.2-2.2; p < 0.001)., Conclusion: PET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.

The optimal methodology for defining response with 18 F-FDG PET after curative-intent chemoradiation for non-small cell lung cancer (NSCLC) is unknown. We compared survival outcomes according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC), PERCIST 1.0, the Peter Mac metabolic visual criteria, and the Deauville criteria, respectively. Methods: Three prospective trials of chemoradiation for NSCLC, involving baseline and posttreatment 18 F-FDG PET/CT imaging, were conducted between 2004 and 2016. Responses were categorized as complete metabolic response (CMR), partial metabolic response, stable metabolic disease, or progressive metabolic disease. Cox proportional-hazards models and log-rank tests assessed the impact of each response on overall survival (OS). Results: Eighty-seven patients underwent 18 F-FDG PET/CT before and after radical chemoradiation for NSCLC. Follow-up 18 F-FDG PET/CT scans were performed at a median of 89 d (interquartile range, 79-93 d) after radiotherapy. Median follow-up and OS after PET response imaging were 49 and 28 mo, respectively. Interobserver agreements for EORTC, PERCIST, Peter Mac, and Deauville had κ values of 0.76, 0.76, 0.87, and 0.84, respectively. All 4 response criteria were significantly associated with OS. Peter Mac and Deauville showed better fit than EORTC and PERCIST and distinguished better between CMR and non-CMR. Conclusion: All 4 response criteria were highly predictive of OS, but visual criteria showed greater interobserver agreement and stronger discrimination between CMR and non-CMR, highlighting the importance of visual assessment to recognize radiation pneumonitis, changes in lung configuration, and patterns of response., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: There is growing interest in developing individually tailored cancer radiation therapy (RT), wherein patients with high intrinsic radiosensitivity are identified before commencing treatment, to minimize severe adverse reactions. In a previous retrospective study of severely radiosensitive RT patients, we established a functional assay with a high predictive capability. The assay involves ex vivo irradiation of peripheral blood mononuclear cells and analysis of DNA repair using the γ-H2AX assay. It is unknown whether RS is a fixed phenomenon or is modulated under different conditions. We now report the impact of RT on the apparent radiosensitivity, as reflected by the assay., Methods and Materials: Peripheral blood mononuclear cells of 11 patients with non-small cell lung cancer were collected before, during, and after RT. Quantitative parameters derived from the nonlinear regression analysis of γ-H2AX foci were applied to examine the cellular radiation response., Results: Although the repair rate and foci yield remained constant during and after RT, the "unrepairable" component of γ-H2AX foci decreased over the course of treatment in 7 patients, signifying a generally enhanced DNA repair capacity. Interestingly, enhanced repair capacity tended to be associated with a poorer response to RT., Conclusions: Although generalization of these results into normal and tumor tissues warrants further investigation, the findings of this study have important implications in future strategies for identifying radiosensitive individuals before exposure to RT. We can anticipate that the threshold values that will discriminate radiosensitive patients in a future prospective trial will differ from those established in the retrospective study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC.In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy (± systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT.Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1-5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%-51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, including 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5 mm (range 7-9) versus 12 mm (range 6-21), P = 0.005.A significant proportion of patients considered for definitive radiotherapy (+/-chemotherapy) undergoing systematic mediastinal evaluation with EBUS-TBNA in this study have an extent of mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free.

Background: Ga-68-macroaggregated albumin ((68)Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC)., Methods: This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The "perfused" lung volume was defined as all lung parenchyma taking up radiotracer, and the "well-perfused" lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUV max). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters., Results: Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values <.05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P < .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05)., Conclusions: This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans adapted to well-perfused but not perfused functional lung volumes allow for reduction in dose to functional lung using 3D conformal radiotherapy., (© The Author(s) 2015.)

Purpose: To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT)., Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC)., Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment., Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Purpose: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer., Methods: (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients., Results: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P < .001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P = .001) and 1.4 mm for posttreatment (P > .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration., Conclusions: DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose-response assessment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Lung tumor delineation is frequently performed using 3D positron emission tomography (PET)/computed tomography (CT), particularly in the radiotherapy treatment planning position, by generating an internal target volume (ITV) from the slow acquisition PET. We investigate the dosimetric consequences of stereotactic ablative body radiotherapy (SABR) planning on 3D PET/CT in comparison with gated (4D) PET/CT., Methods: In a prospective clinical trial, patients with lung metastases were prescribed 26 Gy single-fraction SABR to the covering isodose. Contemporaneous 3D PET/CT and 4D PET/CT was performed in the same patient position. An ITV was generated from each data set, with the planning target volume (PTV) being a 5-mm isotropic expansion. Dosimetric parameters from the SABR plan derived using the 3D volumes were evaluated against the same plan applied to 4D volumes., Results: Ten lung targets were evaluated. All 3D plans were successfully optimized to cover 99% of the PTV by the 26 Gy prescription. In all cases, the calculated dose delivered to the 4D target was less than the expected dose to the PTV based on 3D planning. Coverage of the 4D-PTV by the prescription isodose ranged from 74.48% to 98.58% (mean of 90.05%). The minimum dose to the 4D-ITV derived by the 3D treatment plan (mean = 93.11%) was significantly lower than the expected dose to ITV based on 3D PET/CT calculation (mean = 111.28%), p < 0.01. In all but one case, the planned prescription dose did not cover the 4D-PET/CT derived ITV., Conclusions: Target delineation using 3D PET/CT without additional respiratory compensation techniques results in significant target underdosing in the context of SABR.

Background and Purpose: To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation/perfusion (V/Q) PET/CT., Materials and Methods: In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters., Results: The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values<0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively., Conclusion: IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Fiducial markers act as visible surrogates of tumor position during image-guided radiotherapy. Marker placement has been attempted percutaneously but is associated with high rates of pneumothorax and chest drain placement., Methods: Patients undergoing radical radiation treatment for non-small-cell lung cancer underwent bronchoscopic implantation of gold fiducials using radial probe endobronchial ultrasound (EBUS) with virtual bronchoscopy and fluoroscopic guidance to achieve tumor localization and placement within/adjacent to peripheral lung tumors. For tumors not localized using radial EBUS, fiducial placement was achieved by electromagnetic navigation to the vicinity of the tumor., Results: Eighteen fiducials were placed to mark 16 lesions in 15 patients. In nine patients (60%), fiducials were implanted at the time of diagnostic bronchoscopy. No procedural complications occurred. EBUS localization allowed marker implantation within the target lesion in 12 cases. In four lesions, electromagnetic navigation bronchoscopy-guided implantation achieved a median fiducial-lesion distance of 6 mm (mean 12 mm). No marker migration occurred after the implantation of two-band markers; however, early migration was observed in two of eight (25%) of the smaller linear fiducials. No migration during the course of radiation therapy was observed., Conclusion: Fiducial marker placement is easily and safely performed bronchoscopically, including at the time of diagnostic bronchoscopy. Marker geometry appears important in stability of bronchoscopically inserted fiducials. Future studies are required to confirm the optimal marker size, geometry, and spatial relationship with the target lesion.

Background: Response assessment after stereotactic ablative body radiotherapy (SABR) in lung can be confounded by radiation-induced inflammation, fibrosis and subsequent alteration of tumour motion. The purpose of this prospective pilot study was to evaluate the utility of four-dimensional (4D) FDG-PET/CT for post-SABR tumour and normal lung response assessment in pulmonary oligometastases., Material and Methods: Patients enrolled from February 2010 to December 2011 in this prospective ethics approved study had 1-2 pulmonary metastases on staging FDG-PET. Serial contemporaneous 3D and 4D FDG-PET/CT scans were performed at baseline, 14 days and 70 days after a single fraction of 26 Gy SABR. Tumour response was evaluated in 3D and 4D using SUVmax, RECIST and PERCIST criteria. Normal lung radiotoxicity was evaluated using SUVmean within 0-2 Gy, 2-5 Gy, 5-10 Gy, 10-20 Gy and 20 + Gy isodose volumes., Results: In total, 17 patients were enrolled of which seven were ineligible due to interval progression from staging PET to baseline 4D-PET. The mean time between scans was 62 days. At a median follow-up of 16 months, 10 patients with 13 metastases received SABR, with no patient having local progression. The vector of tumour motion was larger in patients with discordant 3D and 4D PET PERCIST response (p < 0.01), with a mean (± SEM) motion of 10.5 mm (± 0.96 mm) versus 6.14 mm (± 0.81 mm) in those patients with concordant 3D and 4D response. Surrounding normal lung FDG uptake at 70 days was strongly correlated to delivered radiation dose (r(2) = 0.99, p < 0.01), with significant elevations across all dose levels (p ≤ 0.05), except the < 2 Gy volume (p = 0.30)., Conclusions: We demonstrate high rates of interval progression between staging PET scans in patients with oligometastases. We found that tumour response on conventional 3D PET is not concordant with 4D PET for tumours with large motion. Normal lung metabolic uptake is strongly dose dependent after SABR, a novel finding that should be further validated.

Background: Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer deaths. Radiation therapy (RT), alone or in combination with chemotherapy, is the standard of care for curative intent treatment of patients with locally advanced or inoperable NSCLC. The ability to intensify treatment to achieve a better chance for cure is limited by the risk of injury to the surrounding lung., Methods/design: This is a prospective observational study of 60 patients with NSCLC receiving curative intent RT. Independent human ethics board approval was received from the Peter MacCallum Cancer Centre ethics committee. In this research, Galligas and Gallium-68 macroaggregated albumin (MAA) positron emission tomography (PET) imaging will be used to measure ventilation (V) and perfusion (Q) in the lungs. This is combined with computed tomography (CT) and both performed with a four dimensional (4D) technique that tracks respiratory motion. This state-of-the-art scan has superior resolution, accuracy and quantitative ability than previous techniques. The primary objective of this research is to observe changes in ventilation and perfusion secondary to RT as measured by 4D V/Q PET/CT. Additionally, we plan to model personalised RT plans based on an individual's lung capacity. Increasing radiation delivery through areas of poorly functioning lung may enable delivery of larger, more effective doses to tumours without increasing toxicity. By performing a second 4D V/Q PET/CT scan during treatment, we plan to simulate biologically adapted RT depending on the individual's accumulated radiation injury. Tertiary aims of the study are assess the prognostic significance of a novel combination of clinical, imaging and serum biomarkers in predicting for the risk of lung toxicity. These biomarkers include spirometry, (18)F-Fluorodeoxyglucose PET/CT, gamma-H2AX signals in hair and lymphocytes, as well as assessment of blood cytokines., Discussion: By correlating these biomarkers to toxicity outcomes, we aim to identify those patients early who will not tolerate RT intensification during treatment. This research is an essential step leading towards the design of future biologically adapted radiotherapy strategies to mitigate the risk of lung injury during dose escalation for patients with locally advanced lung cancer., Trials Registration: Universal Trial Number (UTN) U1111-1138-4421.

Unlabelled: We aimed to prospectively observe cellular metabolism and proliferation in patients with non-small-cell lung cancer (NSCLC) during radical chemoradiation therapy using serial PET/CT with (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT)., Methods: Twenty patients with stage I-III NSCLC and candidates for radical chemoradiation therapy (60 Gy in 30 fractions over 6 wk) were recruited. (18)F-FDG and (18)F-FLT PET/CT were performed at baseline and during therapy (weeks 2 and 4). Tumor response was assessed semiquantitatively and using visual response criteria., Results: The median and range for primary tumor volume (cm(3)) at baseline on (18)F-FDG were 28 and 2-241, respectively, and on (18)F-FLT 31 and 2-184, respectively. At week 2, (18)F-FDG was 26 (range, 2-164), and (18)F-FLT was 11 (range, 0-111). At week 4, (18)F-FDG was 19 (1-147), and (18)F-FLT was 7 (0-48). The median and range of maximum standardized uptake value (SUVmax) at baseline on (18)F-FDG were 14 and 4-31, respectively, and on (18)F-FLT 6 and 2-12, respectively. Week 2 (18)F-FDG median SUVmax was 10 (2-31), and (18)F-FLT median SUVmax was 3 (1-15); week 4 (18)F-FDG median SUVmax was 10 (2-15), and (18)F-FLT median SUVmax was 2 (2-9). There was fair agreement between visual tumor response on (18)F-FDG and (18)F-FLT during therapy (Cohen's unweighted κ statistic, 0.27 at week 2 and 0.355 at week 4). Cerebral metastases were detected on 1 baseline (18)F-FLT scan, resulting in palliative management. Progressive disease was detected on week 2 scans in 3 patients, resulting in changes to radiation therapy (2 patients) and treatment intent (1 patient)., Conclusion: This study demonstrates that (18)F-FLT PET/CT is a more sensitive tracer of early treatment response than (18)F-FDG PET/CT. The ability of these tracers to detect distinct biologic processes may lead to their use as biomarkers for personalized radiation therapy and prognosis in the future., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Historically, it has been difficult to monitor the acute impact of anticancer therapies on hematopoietic organs on a whole-body scale. Deeper understanding of the effect of treatments on bone marrow would be of great potential value in the rational design of intensive treatment regimens. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a functional radiotracer used to study cellular proliferation. It is trapped in cells in proportion to thymidine-kinase 1 enzyme expression, which is upregulated during DNA synthesis. This study investigates the potential of (18)F-FLT to monitor acute effects of chemotherapy on cellular proliferation and its recovery in bone marrow, spleen, and liver during treatment with 2 different chemotherapy regimens., Methods: Sixty patients with non-small cell lung cancer underwent concurrent radical chemoradiotherapy to 60 Gy in 6 wk with either cisplatin/etoposide (C/E, n = 28) weeks 1 and 5 or weekly carboplatin/paclitaxel (C/P, n = 32) regimens. (18)F-FLT and (18)F-FDG PET with CT were performed at baseline, week 2 (day 9 for (18)F-FLT and day 10 for (18)F-FDG PET), and week 4 (day 23 for (18)F-FLT and day 24 for (18)F-FDG PET). Visual and semiquantitative standardized uptake value (SUV) measurements were performed in bone marrow outside the radiotherapy field, liver, spleen, and small bowel. These were correlated to blood counts and smears in a subset of patients., Results: The C/E group exhibited a drop in bone marrow (18)F-FLT uptake at week 2 (median SUVmax [maximum SUV] decrease to 31%, 8.7-6.0, P < 0.001), with recovery at week 4, reflecting the absence of chemotherapy between these times. By contrast, the weekly C/P group showed gradually declining bone marrow uptake (P > 0.05). Spleen uptake in both cohorts decreased at week 2, with intense rebound activity at week 4 (SUVmax week 4 at 58% above baseline: 2.4-3.8, for C/E, respectively, 30% for C/P: 2.7-3.5, P < 0.001). Liver uptake changed little. (18)F-FLT changes preceded neutrophil count reductions. (18)F-FDG uptake in marrow liver and spleen changed much less than (18)F-FLT., Conclusion: (18)F-FLT imaging may be used to quantify impairment and recovery of bone marrow by specific chemotherapy regimens and may also enable imaging of organ-specific processes such as spleen activation. (18)F-FLT is superior to (18)F-FDG for this purpose. This technology may support novel treatment planning and monitoring approaches in oncology patients., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Aim: A survey of management of lung cancer diagnosed in Victoria in 2003 was commissioned by the Victorian Cooperative Oncology Group to identify gaps in the management of this disease. Results from a similar survey in 1993 were available to identify differences in the disease, management and outcomes. This paper details results of the surgically managed subset within the larger study., Methods: All patients diagnosed with lung cancer in the first 6 months of 2003 were identified from the Victorian Cancer Registry. Registry research staff completed a detailed questionnaire using primary source documents from hospitals and consulting rooms. The survey data were then de-identified with respect to patient and treating clinician prior to statistical analysis by the investigators., Results: From eligible cases identified, non-small cell lung cancer was confirmed in 655 cases with a minimum of 6 years of follow-up. Thoracotomy was performed in 145 cases (22%), but only 130 received the intended resection. Compared with 1993, significant differences were increased use of preoperative positron emission tomography (PET) scanning (79% vs 0%), relatively fewer resections (20% vs 25%), lower pneumonectomy rate (14% vs 25%) and higher sub-lobar resection rate (22% vs 11%). The 30-day mortality remained below 2%. Positive resection margin (21%) and abandoned resection rates (10%) were much higher than expected. Overall 5-year survival was 42%, unchanged from 1993., Conclusion: Irrespective of widespread introduction of PET scanning, thoracotomy without resection was common. While operative mortality and overall survival were well within benchmark standards, futile thoracotomy and positive resection margin rates were unacceptably high., (© 2013 Wiley Publishing Asia Pty Ltd.)

Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients., Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy., Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability., Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Opinion Statement: Brain metastases occur in 20-40 % of lung cancer patients. The use of whole brain radiation therapy (WBRT) has been shown to ameliorate many neurological symptoms, facilitate corticosteroid reduction, enhance quality of life (QOL), and prolong survival. The acute and early delayed side effects of WBRT are generally mild and inconsequential, whereas late complications often are progressive, irreversible, and may have a profound effect on neurocognitive function and QOL. Nevertheless, WBRT remains the cornerstone for treatment of multiple brain metastases due to its efficacy and the paucity of other treatment options. In avoidance of WBRT and its potential toxicity, patients of good performance status and ≤3 metastases may be treated reasonably with focal therapy alone (surgery or radiosurgery) without a compromise in survival. In patients with multiple brain metastases and those undergoing prophylactic cranial irradiation (PCI), established methods to mitigate the late complications of WBRT include total dose observation, dose per fraction restrictions, and avoidance of concomitant chemotherapy. Current areas of active research that hold great potential for benefit include hippocampal-sparing radiotherapy and the use of neuroprotective agents.

Objectives: To identify areas to improve patient management in lung cancer, which remains the greatest cause of death from cancer in Australia., Design and Setting: Retrospective survey of all cases of lung cancer reported to the Victorian Cancer Registry from 1 January to 30 June 2003 and followed up for 5 years., Main Outcome Measures: Patient and disease characteristics, investigations, staging, treatment, cause of death, survival., Results: 841 patients were included. Smoking data were available for 799, of whom 63 (7.9%) had never smoked. Of 655 non-small cell lung cancer (NSCLC) cases, 198 (30.2%) were treated with curative intent, 125 (19.1%) by surgery and 73 (11.1%) by radiotherapy with or without chemotherapy. Only 7 (6.9%) of surgical patients with complete R0 resection had adjuvant chemotherapy. Of 101 small cell lung cancer (SCLC) cases, a third had limited stage disease which was mostly treated with curative intent by chemotherapy with or without radiotherapy. Patients whose cases were discussed at a multidisciplinary meeting (MDM) were significantly more likely to receive anticancer treatment and had longer survival; on multivariate analysis, MDM discussion was an independent prognostic factor. Compared with a similar survey 10 years earlier, the median age of patients diagnosed with lung cancer had increased by almost 3 years, the proportion of affected men decreased and adenocarcinoma was more frequent, while 10% of patients continued to have no pathologically confirmed diagnosis and 26% continued to receive no anticancer treatment. The number of patients with NSCLC who went on to a definitive surgical procedure fell with no detriment to survival, which likely reflected better staging with the introduction of positron emission tomography scanning., Conclusions: Opportunities to improve patient management included increasing the proportion with a pathologically confirmed diagnosis and greater use of postsurgical adjuvant chemotherapy. A high proportion of patients received no treatment, with underuse of chemotherapy and radiotherapy. Critically, the low rate of case discussions at MDMs needs to increase. However, effective strategies are required to identify cases early, as over two-thirds currently present with incurable disease.

Background and Purpose: To investigate the hypothesis that primary tumor volume is prognostic independent of T and N stages in patients with non-small cell lung cancer (NSCLC) treated by definitive radiotherapy., Materials and Methods: Multicenter prospective observational study. Patient eligibility: pathologically proven stage I-III non-small cell lung cancer planned for definitive radiotherapy (minimum 50 Gy in 20 fractions) using CT-based contouring. Volumes of the primary tumor and enlarged nodes were measured according to a standardized protocol. Survival was adjusted for the effect of T and N stage., Results: There were 509 eligible patients. Five-year survival rates for tumor volume grouped by quartiles were, for increasing tumor volume, 22%, 14%, 15% and 21%. Larger primary tumor volume was associated with shorter survival (HR=1.060 (per doubling); 95% CI 1.01-1.12; P=0.029). However, after adjusting for the effects of T and N stage, there was no evidence for an association (HR=1.029, 95% CI, 0.96-1.10, P=0.39). There was evidence, however, that larger primary tumor volume was associated with an increased risk of dying, independently of T and N stage, in the first 18 months but not beyond., Conclusions: In patients treated by non-surgical means we were unable to show that lung tumor volume, overall, provides additional prognostic information beyond the T and N stage (TNM, 6th edition). There is evidence, however, that larger primary tumor volume adversely affects outcome only within the first 18 months. Larger tumor size alone should not by itself exclude patients from curative (chemo)radiotherapy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: We investigated the incremental management impact and prognostic value of staging with (18)F-FDG PET/CT in patients with non-small cell lung cancer (NSCLC) being considered for potentially curative therapies., Methods: Information on 168 consecutive patients with NSCLC being considered for surgery or definitive radiotherapy with curative intent before PET/CT was entered into a prospective database. The pre-PET/CT management plan, based on conventional imaging (conventional CT, appropriately supplemented by bone scintigraphy or other modalities), was defined prospectively by referring clinicians before PET/CT results became available. After PET/CT, actual clinical management was recorded, and patients were followed up until 5 y or death. The appropriateness of PET/CT management plans was assessed by biopsy when available, clinical follow-up, and survival analysis., Results: Stage was discordant on PET/CT and conventional imaging in 50.6% of patients (41.1% upstaged, 9.5% downstaged), with high management impact (change in treatment modality or curative intent) in 42.3% of patients. Both conventional imaging stage and PET/CT stage were strongly predictive of overall survival (OS) but there were greater differences between hazard rates and separations in the OS curves for stage groupings determined using PET/CT. OS was also strongly predicted by PET/CT-directed choice of therapy (P < 0.0001)., Conclusion: PET/CT frequently affects patient management and strongly predicts OS in NSCLC, supporting the appropriateness of such changes.

Introduction: This study aimed to establish from the published literature the efficacy of a positron emission tomography (PET)-based strategy for the staging of small-cell lung cancer compared to conventional methods, the potential impact on patient management and outcomes, and cost implications for the Australian health system., Methods: EMBASE, Current Contents, PubMed, and OVID, databases were searched using relevant search terms. Reference lists of identified studies were examined for additional pertinent papers. Literature review identified 22 relevant studies containing data for 1663 patients. Studies were evaluated regarding the adequacy of pathological or clinical correlation of imaging findings. Efficacy of PET-staging was analyzed. The Medicare benefits schedule was used to compare costs of the two strategies., Results: Published data confirm that PET staging has a sensitivity approaching 100% and specificity exceeding 90%. Data suggest that compared to conventional staging, PET can alter management (including radiotherapy portal changes) in at least 28% of patients, can result in the addition of life-prolonging radiotherapy in 6%, and avert unnecessary radiotherapy with associated toxicity in 9%. PET-based staging costs 1603 Australian dollars (AUD) and conventional staging 1610 AUD per patient. An additional 540,354 AUD may be saved annually through avoidance of unnecessary radiotherapy., Conclusions: PET-based staging seems superior to conventional staging, and can significantly alter patient management particularly with regard to the inclusion, omission, and portal design of radiotherapy. The initial costs of the two strategies do not seem significantly different. PET may ultimately reduce healthcare costs through avoidance of inappropriate thoracic radiotherapy. The major advantages of PET-staging may, however, lie in averting unnecessary toxicity and in the appropriate addition of thoracic radiotherapy with potential survival gains.

Purpose: To study the relationship between fluorodeoxyglucose (FDG) uptake in pulmonary tissue after radical radiation therapy (RT) and the presence and severity of radiation pneumonitis., Methods and Materials: In 88 consecutive patients, (18)F-FDG-positron emission tomography was performed at a median of 70 days after completion of RT. Patients received 60 Gy in 30 fractions, and all but 15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory changes occurring within the radiation treatment volume were scored, using a visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by an observer blinded to the PET radiotoxicity score., Results: There was a significant association between the worst RTOG pneumonitis grade occurring at any time after RT and the positron emission tomograph (PET) radiotoxicity grade (one-sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For every one-level increase in the PET toxicity scale, the risk of a higher RTOG radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity score showed no significant correlation with the duration of radiation pneumonitis., Conclusions: The intensity of FDG uptake in pulmonary tissue after RT determined using a simple visual scoring system showed significant correlation with the presence and severity of radiation pneumonitis. (18)F-FDG-PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To measure long-term survival following combined chemotherapy and radiotherapy for inoperable non-small cell lung cancer., Design and Setting: Two prospective Phase I/II studies in the multidisciplinary Lung Service of a dedicated cancer hospital in Victoria, commencing in 1996 and 1997-1998., Patients: 33 patients referred for treatment of histologically or cytologically proven inoperable non-small cell lung cancer, who had no evidence of distant metastases, Karnofsky performance status > 70%, weight loss < 10%, and no prior treatment for lung cancer. Patients were followed until death or for a minimum of 9 years., Interventions: Patients in both studies were treated concomitantly with chemotherapy and radiotherapy 60 Gy in 30 fractions over 6 weeks. Chemotherapy in the first study (LURTCE) consisted of cisplatin and etoposide; in the second study (LURTCF), chemotherapy consisted of escalating doses of carboplatin and fluorouracil., Main Outcome Measure: Overall survival., Results: Six of 33 patients were still alive 9 years after commencement of treatment. Median survival for the whole group was 2.1 years (95% CI, 1.3-3.1 years), with 18% (95% CI, 8%-35%) of patients still alive at 5 years (plateau)., Conclusion: Long-term survival can be achieved in some patients with inoperable non-small cell lung cancer treated by radical chemoradiation alone, suggesting the possibility of cure.

Background: Tumor volume has been shown to be a prognostic factor for the response of some tumors to radiotherapy. TNM stage has prognostic value for patients treated surgically for non-small cell lung cancer (NSCLC), but its value is less clear for patients treated by nonsurgical means. This may be because tumor size is not a consistent determinant of T stage or stage group. As part of the preliminary analyses for the Trans-Tasman Radiation Oncology Group 99-05 study, the authors performed this analysis to determine to what extent stage reflects tumor volume., Methods: In this prospective multicenter observational study, patients had to have histologically proven NSCLC, no evidence of disease beyond the primary site or thoracic lymph nodes, and been planned for radical radiotherapy with or without chemotherapy. Tumor volume measurements were based on computed tomography-based treatment planning images., Results: Four hundred four patients were available for analysis. There was a strong correlation between (log) maximum tumor diameter and (log) tumor volume (r = 0.93, p < 0.001). Although there was a highly significant trend of increasing volume with increasing T stage and stage group, when tumors were categorized into four groups according to increasing volume, there was only 55% concordance with T stage and 67% concordance with stage group., Conclusions: There is limited correlation between tumor size and disease stage in patients with NSCLC. This justifies documentation and investigation of size as a potential prognostic factor independent of stage. Maximum tumor diameter may be an adequate substitute for volume as a measurement of size.

Background: Many experienced oncologists have encountered patients with proven non-small cell lung cancer (NCLC) who received modest doses of palliative radiotherapy (RT) and who unexpectedly survived for > 5 years; some were apparently cured. We used a very large prospective database to estimate the frequency of this phenomenon and to look for correlative prognostic factors., Methods: Patients with histologically or cytologically proven NSCLC, treated with palliative RT to a dose of < or = 36 Gy, were identified from a prospective database containing details of 3035 new patients registered from 1984-1990., Results: An estimated 1.1% (95% confidence interval, 0.7-1.6%) of 2337 palliative RT patients survived for 5 or more years after commencement of RT, including 18 patients who survived progression-free for 5 years. Estimated median survival was 4.6 months. Five-year survivors had significantly better Eastern Cooperative Oncology Group performance status at presentation than non-5-year survivors (P = 0.024) and were less likely to have distant metastases (P = 0.020). RT dose did not appear to be a significant prognostic factor. Patients who survived 5 years without progression had an estimated 78% probability of remaining free from progression in the next 5 years., Conclusions: Approximately 1% of patients with proven NSCLC survived for > 5 years after palliative RT, and many of these patients appeared to have been cured by a treatment usually considered to be without curative potential. Because of the potential for long-term survival, doses to late-reacting normal tissues should be kept within tolerance when prescribing palliative RT in NSCLC.

Background: We previously reported that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) response correlated strongly with survival after radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer (NSCLC). PET-response, survival and patterns of failure data are presented with long-term follow-up., Methods: Pre- and post-treatment FDG-PET scans were performed for 88 patients after concurrent platinum-based radical chemo/RT (n = 73) or radical RT alone (n = 15). PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD)., Results: RT was 60 Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median of 70 days after treatment. PET responses were: CMR, n = 40 (45%); PMR, n = 32 (36%); SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow-up PET was 23 months; median follow-up duration 35 months. One and 2 year survival after follow-up PET was 68% and 45%, respectively. Median survival for CMR and non-CMR patients was 31 and 11 months, respectively (p = 0.0001). One-year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2 years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR patients had higher rates of local failure (HR 2.15, p = 0.009) and distant metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR patients (50%) had PMD, with local failure (n = 8), distant metastasis (n = 2) or both (n = 10)., Conclusions: Attainment of CMR after radical RT/chemoRT for NSCLC bestows superior freedom from local and distant relapse; late local relapse is common.

F-18 fluorodeoxyglucose-positron emission tomography (PET) was investigated in patients with suspected residual disease or intrathoracic recurrence after pneumonectomy. Patients were identified from a prospective database. Impact of PET on staging and patient management was assessed. Clinical outcome was used to assess appropriateness of management. PET was performed in 17 cases, either post-operatively (n = 8), or later for suspected recurrence (n = 9) in patients with good performance status and without extensive disease on conventional imaging. PET changed treatment in 10 cases (59%). In five patients (29%), PET changed treatment intent (curative versus non-curative) from radical radiotherapy (RT) to palliative RT (n = 1), or observation or supportive care (n = 3), or from palliative to radical RT (n = 1). In a further patient with unexplained pain, PET appropriately showed no evidence of disease. In additional five cases (29%), PET influenced choice of RT dose and the use of concurrent chemotherapy (n = 3) or target volume (n = 2). Patients without tumour or with limited disease on PET had favourable outcomes whereas those with extensive disease suffered early tumour progression. PET was discordant with conventional assessment in >50% of cases. PET may be valuable after pneumonectomy if the patient is being considered for adjuvant or salvage radiotherapy although specificity may be reduced due to post-operative inflammatory changes.

Study Objectives: To quantify clinician knowledge and bias regarding the role of chemotherapy for stage IV non-small cell lung cancer (NSCLC)., Design, Setting, and Participants: A 16-question, multiple-choice questionnaire was sent to all Australian general internists, pulmonary and palliative care physicians, medical and radiation oncologists, and thoracic surgeons to assess beliefs concerning the role of chemotherapy in metastatic NSCLC. An overall assessment of "pessimism" and "optimism" regarding the role of chemotherapy in metastatic NSCLC was made, and knowledge of specific outcome measures was evaluated., Measurements and Results: A total of 1,325 questionnaires were mailed, with 679 replies (51%) received and 544 replies (41%) assessable. Overall, 60% of respondents were deemed to have good knowledge. There was a wide variation in knowledge between specialist groups (p < 0.0001), with more medical oncologists (76%) but fewer thoracic surgeons (35%) and general internists (50%) with good knowledge. Fewer medical oncologists (6%) were classified as pessimistic compared with palliative care physicians (31%), radiation oncologists (28%), or pulmonary physicians (22%). Sixty-eight percent of respondents agreed that most patients receiving chemotherapy have symptomatic improvement. More medical oncologists (77%) and pulmonary physicians (73%), but fewer general internists (55%) and palliative care physicians (57%) agreed with this. Medical oncologists were far more likely to agree that chemotherapy was of benefit in patients aged > or = 70 years compared with any of the other specialist groups., Conclusions: There were significant differences regarding the perceived role of chemotherapy in metastatic disease between the various specialty groups involved in the treatment of NSCLC. Many clinicians had a poor understanding of contemporary data regarding the use of chemotherapy in metastatic NSCLC. This study raises substantial issues regarding the beliefs of clinicians treating NSCLC and emphasizes the importance of multidisciplinary assessment.

Purpose: To determine if the addition of carboplatin chemotherapy to whole brain irradiation improves response and survival in patients with brain metastases from non-small cell lung cancer (NSCLC)., Patients and Methods: Forty-two patients with brain metastases from NSCLC and performance status ECOG 0-2 were randomised to receive either whole brain radiotherapy (WBRT) alone (20Gy in five fractions) or the same radiotherapy plus concomitant carboplatin (70 mg/m(2) intravenously for 5 days)., Results: The median survival was 4.4 months in the radiotherapy alone (RT) arm and 3.7 months in the combined treatment (RTC) arm (P = 0.64). The objective response rates of 10% on the RT arm and 29% on the RTC arm were not significantly different (P = 0.24). The trial was closed early because of poor accrual., Conclusions: Although no firm conclusions can be made regarding the efficacy of the combined treatment, this prospective study highlights the poor objective response rates and relatively poor symptom control despite standard treatment of brain metastases from NSCLC.

Purpose: To investigate the relationship between positron emission tomography (PET) detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy for non-small-cell lung cancer. The prognostic significance of these changes was also studied., Methods: In 73 consecutive patients, (18)F-fluorodeoxyglucose (FDG) PET was performed at a median of 70 days after completion of radical radiotherapy. Radiation-induced inflammatory change was scored for normal tissues within the radiation treatment volume using a 0-3 grading scale. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and posttreatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model., Results: Increased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial tumor response on both PET (p = 0.0044) and computed tomography (p = 0.029). Prognostic stratification provided by PET response was both significant and of a similar magnitude in patients with low- and high-grade radiotoxicity., Conclusion: Postradiotherapy inflammatory changes detected by FDG-PET are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET is not compromised by inflammatory changes if a meticulous visual response assessment technique is used.

Purpose: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non-small-cell lung cancer (NSCLC)., Patients and Methods: Seventy-three patients with NSCLC underwent [(18)F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival., Results: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P <.0001)., Conclusion: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.

The prognostic significance of extracranial distant metastasis detected by positron emission tomography (PET) was investigated in patients with non-small cell lung cancer (NSCLC). Forty-two patients staged with 18F-fluorodeoxyglucose-PET-detected distant metastasis before planned surgery (n = 7) or radical radiotherapy (RT)/chemoradiotherapy (n = 35) for NSCLC were identified from a prospective database. The influence of metastasis number and other prognostic factors was investigated using Cox's regression analysis. Treatment after PET included surgery (n = 2), radical RT (n = 5), palliative RT (n = 25), chemotherapy (n = 8) or supportive care (n = 2). All but 4 patients had died by the last follow-up. Median survival was 9 months overall, 12 months for 27 patients with single PET-detected metastasis and 5 months for 15 patients with > 1 metastasis (p = 0.009). It was found that the Eastern Cooperative Oncology Group performance status (p = 0.027) but not pre-PET stage, weight loss or metastasis site correlated with survival. PET-detected metastatic tumor burden appeared to influence survival and should be evaluated as a prognostic factor in NSCLC.

Purpose: At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients., Methods and Materials: Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I--III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss., Results: Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss; 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p = 0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival., Conclusion: Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging.