Nikki Plumridge

High rates of tumor growth and disease progression detected on serial pretreatment fluorodeoxyglucose-positron emission tomography/computed tomography scans in radical radiotherapy candidates with nonsmall cell lung cancer.

The authors studied growth and progression of untreated nonsmall cell lung cancer (NSCLC) by comparing diagnostic and radiotherapy (RT) planning fluorodeoxyglucose (FDG)‐positron emission tomography (PET)/computed tomography (CT) scans before proposed radical chemo‐RT.

The use of fused PET/CT images for patient selection and radical radiotherapy target volume definition in patients with non-small cell lung cancer: Results of a prospective study with mature survival data

BACKGROUND AND PURPOSE This prospective study investigated the impact of radiotherapy (RT)-planning FDG-PET/CT on management of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Patients still eligible for radical RT after conventional staging underwent RT-planning PET/CT and, if disease was still treatable to 60 Gy, they entered our planning study, where visually-contoured tumour volumes derived with and without PET information were compared. If PET/CT detected advanced disease, palliative therapy was given. Overall survival (OS) for palliative and curative patients was compared. RESULTS Of 76 eligible patients, only 50 (66%) received radical chemoRT after PET/CT while 26 (34%) received palliative therapies because PET/CT detected advanced disease. Without PET, FDG-avid tumour would reside outside the planning target volume (PTV) in 36% of radical cases and in 25% <90% of the PTV would have received >95% prescribed dose. OS for all patients was 56.8% and 24.9% at 1 and 4 years, respectively. OS for patients given chemoRT was 77.5% and 35.6% at 1 and 4 years, respectively and was 32% for stage IIIA patients at 4 years. OS for patients treated palliatively was inferior (P<0.001); 16.3% and 4.1% at 1 and 4 years, respectively. CONCLUSIONS Planning PET/CT frequently changed management and was associated with excellent survival. Survival data from this study were presented in part at the 2011 World Lung Cancer Conference, Amsterdam and planning data at the 2010 Annual Scientific Meeting of the American Society for Therapeutic Radiology and Oncology, Chicago.

Differential 18F-FDG and 18F-FLT Uptake on Serial PET/CT Imaging Before and During Definitive Chemoradiation for Non–Small Cell Lung Cancer

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 18F-FDG and 3′-deoxy-3′-18F-fluorothymidine (18F-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. 18F-FDG and 18F-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 (cm3) at baseline on 18F-FDG were 28 and 2–241, respectively, and on 18F-FLT 31 and 2–184, respectively. At week 2, 18F-FDG was 26 (range, 2–164), and 18F-FLT was 11 (range, 0–111). At week 4, 18F-FDG was 19 (1–147), and 18F-FLT was 7 (0–48). The median and range of maximum standardized uptake value (SUVmax) at baseline on 18F-FDG were 14 and 4–31, respectively, and on 18F-FLT 6 and 2–12, respectively. Week 2 18F-FDG median SUVmax was 10 (2–31), and 18F-FLT median SUVmax was 3 (1–15); week 4 18F-FDG median SUVmax was 10 (2–15), and 18F-FLT median SUVmax was 2 (2–9). There was fair agreement between visual tumor response on 18F-FDG and 18F-FLT during therapy (Cohens unweighted κ statistic, 0.27 at week 2 and 0.355 at week 4). Cerebral metastases were detected on 1 baseline 18F-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 18F-FLT PET/CT is a more sensitive tracer of early treatment response than 18F-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.

The impact of time between staging PET/CT and definitive chemo-radiation on target volumes and survival in patients with non-small cell lung cancer

BACKGROUND AND PURPOSE To investigate the impact of treatment delays on radiation therapy (RT) target volumes and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who underwent two baseline FDG PET/CT scans. MATERIAL AND METHODS Patients underwent a staging (PET1) and RT planning (PET2) FDG PET/CT scan. At PET1 all patients were eligible for radical chemo-RT. OS and progression-free survival (PFS) were compared for patients remaining eligible for radical RT and those treated palliatively because PET2 showed progression. RT target volumes were contoured using PET1 and PET2. Normal tissue doses were compared for patients remaining eligible for radical RT. RESULTS Eighty-two patients underwent PET2 scans between October 2004 and February 2007. Of these, 21 had a prior PET1 scan, median 23 days apart (range 8-176 days). Six patients (29%) were unsuitable for radical RT after PET2; five received palliative treatment and one received no treatment. Patients treated palliatively had significantly worse OS and PFS than patients treated radically p<0.001. Mean RT tumour volume increased from 105cc to 198cc (p<0.005) between scans. CONCLUSIONS Disease progression while awaiting initiation of curative RT in NSCLC is associated with larger treatment volumes and worse survival.

Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung.

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.

Ga-68 MAA Perfusion 4D-PET/CT Scanning Allows for Functional Lung Avoidance Using Conformal Radiation Therapy Planning

Background: Ga-68-macroaggregated albumin (68Ga-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 (SUVmax). 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.

Cone‐beam computed tomography for lung cancer – validation with CT and monitoring tumour response during chemo‐radiation therapy

Cone‐beam computed tomography (CBCT) is a valuable image‐guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non‐small cell lung cancer (NSCLC) tumour volumes compared to the anatomical ‘gold standard’, CT. Tumour regression or progression on CBCT was also analysed.

Preoperative chemotherapy for non-small-cell lung cancer

232 www.thelancet.com Vol 384 July 19, 2014 rates following chemotherapy range from 2% to 14%. While the authors have provided information on incomplete resection rates, no information has been provided on disease progression rates during preoperative chemotherapy and subsequent operabil ity rates. Quantifying this risk would be useful for patients and clinicians in making decisions regarding the timing of chemotherapy. Although the meta-analysis indicates an overall population survival benefit of preoperative chemotherapy, the question remains whether the subset of patients who progress might have benefitted more from the sequence of defi nitive surgery followed by adjuvant chemotherapy. At an individual patient level, the lost opportunity for curative resection can be devastating. Given the risk of disease progression with preoperative systemic therapy, the comparable outcomes with adjuvant systemic therapy and the fact that primary surgical resection provides accurate pathological staging rather than clinical staging, our preferred approach is to recommend surgery followed by adjuvant chemotherapy.