Early CT and FDG-metabolic tumour volume changes show a significant correlation with survival in stage I-III small cell lung cancer: A hypothesis generating study

BACKGROUND: Many patients with stage I–III small cell lung cancer (SCLC) experience disease progression short after the completion of concurrent chemoradiotherapy (CRT). The purpose of the current study was to evaluate whether CT or FDG metabolic response early after the start of chemotherapy, but before the beginning of chest RT, is predictive for survival in SCLC. METHODS: Fifteen stage I–III SCLC patients treated with concurrent CRT with an FDG-PET and CT scan available before the start of chemotherapy and after or during the first cycle of chemotherapy, but before the start of radiotherapy, were selected. The metabolic volume (MV) was defined both within the primary tumour and in the involved nodal stations using the 40% (MV40) and 50% (MV50) threshold of the maximum SUV. Metabolic and CT response was assessed by the relative change in MV and CT volume, respectively, between both time points. The association between response and overall survival (OS) was analysed by univariate cox regression analysis. The minimum follow-up was 18 months. RESULTS: Reductions in MV40 and MV50 were −36 ± 38% (126.4 to 68.7 cm(3)) and −44 ± 38% (90.2 to 27.8 cm(3)), respectively. The median CT volume reduction was −40 ± 64% (190.6 to 113.8 cm(3)). MV40 and MV50 changes showed a significant association with survival (HR = 1.02, 95% CI: 1.00–1.04 (p = 0.042); HR = 1.02, 95% CI: 1.00–1.04 (p = 0.048), respectively), indicating a 2% increase in survival probability for 1% reduction in metabolic volume. The CT volume change was also significantly correlated with survival (HR = 1.01, 95% CI: 1.00–1.03, p = 0.007). CONCLUSIONS: This hypothesis generating study shows that both the early CT and the MV changes show a significant correlation with survival in SCLC. A prospective study is planned in a larger patient cohort to allow multivariate analysis, with the final aim to select patients early during treatment that could benefit from dose intensification or alternative treatment

Visually guided inspiration breath-hold facilitated with nasal high flow therapy in locally advanced lung cancer

Background and purpose Reducing breathing motion in radiotherapy (RT) is an attractive strategy to reduce margins and better spare normal tissues. The objective of this prospective study (NCT03729661) was to investigate the feasibility of irradiation of non-small cell lung cancer (NSCLC) with visually guided moderate deep inspiration breath-hold (IBH) using nasal high-flow therapy (NHFT). Material and methods Locally advanced NSCLC patients undergoing photon RT were given NHFT with heated humidified air (flow: 40 L/min with 80% oxygen) through a nasal cannula. IBH was monitored by optical surface tracking (OST) with visual feedback. At a training session, patients had to hold their breath as long as possible, without and with NHFT. For the daily cone beam CT (CBCT) and RT treatment in IBH, patients were instructed to keep their BH as long as it felt comfortable. OST was used to analyze stability and reproducibility of the BH, and CBCT to analyze daily tumor position. Subjective tolerance was measured with a questionnaire at 3 time points. Results Of 10 included patients, 9 were treated with RT. Seven (78%) completed the treatment with NHFT as planned. At the training session, the mean BH length without NHFT was 39 s (range 15-86 s), and with NHFT 78 s (range 29-223 s) (p = .005). NHFT prolonged the BH duration by a mean factor of 2.1 (range 1.1-3.9s). The mean overall stability and reproducibility were within 1 mm. Subjective tolerance was very good with the majority of patients having no or minor discomfort caused by the devices. The mean inter-fraction tumor position variability was 1.8 mm (-1.1-8.1 mm;SD 2.4 mm). Conclusion NHFT for RT treatment of NSCLC in BH is feasible, well tolerated and significantly increases the breath-hold duration. Visually guided BH with OST is stable and reproducible. We therefore consider this an attractive patient-friendly approach to treat lung cancer patients with RT in BH

PET imaging of hypoxia using [F-18]HX4: a phase I trial

 Download the images using these instructions and this DOI : 10.1007/s00259-010-1437-x Background and purposeNon-invasive PET imaging of tumour hypoxia could help in the selection of those patients who could benefit from chemotherapy or radiation with specific antihypoxic treatments such as bioreductive drugs or hypoxic radiosensitizers. In this phase I trial, we aimed to determine the toxicity of [18F]HX4, a member of the 2-nitroimidazole family, at different dose levels. The secondary aim was to analyse image quality related to the HX4 dose and the timing of imaging.MethodsPatients with a..

Acuros(R)dose verification of ultrasmall lung lesions with EBT-XD film in a homogeneous and heterogeneous anthropomorphic phantom setup

Purpose Modern type 'c' dose calculation algorithms like Acuros(R)can predict dose for lung tumors larger than approximately 4 cm(3)with a relative uncertainty up to 5%. However, increasingly better tumor diagnostics are leading to the detection of very small early-stage lung tumors that can be treated with stereotactic body radiotherapy (SBRT) for inoperable patients. This raises the question whether dose algorithms like Acuros(R)can still accurately predict dose within 5% for challenging conditions involving small treatment fields. Current recommendations for Quality Assurance (QA) and dose verification in SBRT treatments are to use phantoms that are as realistic as possible to the clinical situation, although water-equivalent phantoms are still largely used for dose verification. In this work we aim to demonstrate that existing dose verification methods are inadequate for accurate dose verification in very small lung tumors treated with SBRT. Method The homogeneous PTW Octavius4D phantom with the Octavius 1000 SRS detector ("Octavius4D phantom") and the heterogeneous CIRS Dynamic Thorax phantom ('CIRS phantom') were used for dose measurements. The CIRS phantom contained different lung-equivalent film-holding cylindrical phantom inserts ("film inserts") with water-equivalent spherical targets with diameters 0.5, 0.75, 1, 2, and 3 cm. Plans were calculated for 6 and 10 MV for each spherical target in the CIRS phantom, resulting in 14 treatment plans. The plans were delivered to both Octavius4D and CIRS phantom to compare measured dose in a commonly used homogeneous and more realistic heterogeneous phantom setup. In addition, treatment plans of seven clinical lung cancer patients with lung tumors below approximately 1.0 cm(3)were irradiated in the heterogeneous CIRS phantom. The actual tumor size within the clinical treatment plans determined the choice of the spherical target size, such that both measurement geometry and clinical target volumes match as closely as possible. The Acuros(R)dose algorithm (version 15.5.11) was used for all dose calculations reporting dose-to-medium using a 0.1-cm-grid size. Results The measurement discrepancies in the homogeneous Octavius4D phantom for the fourteen treatment plans were within 1.5%. Dose discrepancies between measurement and treatment planning systems (TPS) for the heterogeneous CIRS phantom increased for both 6 and 10 MV with decreasing target diameters up to 23.7 +/- 1.0% for 6 MV and 8.8 +/- 1.1% for 10 MV for the smallest target of 0.5 cm in diameter with a 2-mm-CTV-PTV margin. For the seven clinical plans this trend of increasing dose difference with decreasing tumor size is less pronounced although the smallest tumors show the largest differences between measurement and TPS up to 16.6 +/- 0.9%. Conclusion Current verification methods using homogenous phantoms are not adequate for lung tumors with diameters below approximately 0.75 cm. The current Acuros(R)dose calculation algorithm underestimates dose in very small lung tumors. Dose verification of small lung tumors should be performed in an anthropomorphic lung phantom incorporating a water-equivalent target that matches clinical tumor size as closely as possible.</p

Response Assessment Using F-18-FDG PET Early in the Course of Radiotherapy Correlates with Survival in Advanced-Stage Non-Small Cell Lung Cancer

This study investigates the possibility of early response assessment based on the FDG-uptake during (chemo-)radiotherapy with respect to overall survival in non-small cell lung cancer. METHODS: FDG-PET/CT imaging was performed prior to radiotherapy and repeated in the second week of radiotherapy treatment for 34 consecutive lung cancer patients treated with (chemo-)radiotherapy. CT volume and SUV parameters of the primary tumor were quantified on both time points. Changes in volume and SUV parameters were correlated to two-year overall survival. RESULTS: The average decrease of mean SUV in the primary tumor of patients with a 2-year survival was 19±16% and significantly higher (p<0.001) compared to the non-survivors with an increase of 2±12%. A sensitivity and specificity of 63% and 93%, respectively, to separate the two groups was reached for a decrease in mean SUV of 15%. Survival curves were different using this cut-off value (p=0.001). The hazard ratio for a 1% decrease in SUV mean was 1.032 (95% CI: 1.010 – 1.055). Changes in tumor volume defined on CT were not correlated to overall survival. CONCLUSION: Early treatment response assessment during radiotherapy with repeated FDG-PET imaging is possible in sequential chemo-radiation as well as concurrent chemo-radiation therapy. A decrease in FDG uptake of the primary tumor correlates with higher long-term overall survival