Sorting lung tumor volumes from 4D-MRI data using an automatic tumor-based signal reduces stitching artifacts.

PURPOSE: To investigate whether a novel signal derived from tumor motion allows more precise sorting of 4D-magnetic resonance (4D-MR) image data than do signals based on normal anatomy, reducing levels of stitching artifacts within sorted lung tumor volumes. METHODS: (4D-MRI) scans were collected for 10 lung cancer patients using a 2D T2-weighted single-shot turbo spin echo sequence, obtaining 25 repeat frames per image slice. For each slice, a tumor-motion signal was generated using the first principal component of movement in the tumor neighborhood (TumorPC1). Signals were also generated from displacements of the diaphragm (DIA) and upper and lower chest wall (UCW/LCW) and from slice body area changes (BA). Pearson r coefficients of correlations between observed tumor movement and respiratory signals were determined. TumorPC1, DIA, and UCW signals were used to compile image stacks showing each patient's tumor volume in a respiratory phase. Unsorted image stacks were also built for comparison. For each image stack, the presence of stitching artifacts was assessed by measuring the roughness of the compiled tumor surface according to a roughness metric (Rg). Statistical differences in weighted means of Rg between any two signals were determined using an exact permutation test. RESULTS: The TumorPC1 signal was most strongly correlated with superior-inferior tumor motion, and had significantly higher Pearson r values (median 0.86) than those determined for correlations of UCW, LCW, and BA with superior-inferior tumor motion (p < 0.05). Weighted means of ratios of Rg values in TumorPC1 image stacks to those in unsorted, UCW, and DIA stacks were 0.67, 0.69, and 0.71, all significantly favoring TumorPC1 (p = 0.02-0.05). For other pairs of signals, weighted mean ratios did not differ significantly from one. CONCLUSION: Tumor volumes were smoother in 3D image stacks compiled using the first principal component of tumor motion than in stacks compiled with signals based on normal anatomy.

The Diagnostic Value of MR Imaging in Determining the Lymph Node Status of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis.

Purpose To summarize existing evidence of thoracic magnetic resonance (MR) imaging in determining the nodal status of non-small cell lung cancer (NSCLC) with the aim of elucidating its diagnostic value on a per-patient basis (eg, in treatment decision making) and a per-node basis (eg, in target volume delineation for radiation therapy), with results of cytologic and/or histologic examination as the reference standard. Materials and Methods A systematic literature search for original diagnostic studies was performed in PubMed, Web of Science, Embase, and MEDLINE. The methodologic quality of each study was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies 2, or QUADAS-2, tool. Hierarchic summary receiver operating characteristic curves were generated to estimate the diagnostic performance of MR imaging. Subgroup analyses, expressed as relative diagnostic odds ratios (DORs) (rDORs), were performed to evaluate whether publication year, methodologic quality, and/or method of evaluation (qualitative [ie, lesion size and/or morphology] vs quantitative [eg, apparent diffusion coefficients in diffusion-weighted images]) affected diagnostic performance. Results Twelve of 2551 initially identified studies were included in this meta-analysis (1122 patients; 4302 lymph nodes). On a per-patient basis, the pooled estimates of MR imaging for sensitivity, specificity, and DOR were 0.87 (95% confidence interval [CI]: 0.78, 0.92), 0.88 (95% CI: 0.77, 0.94), and 48.1 (95% CI: 23.4, 98.9), respectively. On a per-node basis, the respective measures were 0.88 (95% CI: 0.78, 0.94), 0.95 (95% CI: 0.87, 0.98), and 129.5 (95% CI: 49.3, 340.0). Subgroup analyses suggested greater diagnostic performance of quantitative evaluation on both a per-patient and per-node basis (rDOR = 2.76 [95% CI: 0.83, 9.10], P = .09 and rDOR = 7.25 [95% CI: 1.75, 30.09], P = .01, respectively). Conclusion This meta-analysis demonstrated high diagnostic performance of MR imaging in staging hilar and mediastinal lymph nodes in NSCLC on both a per-patient and per-node basis. (©) RSNA, 2016 Online supplemental material is available for this article.

Should breathing adapted radiotherapy also be applied for right-sided breast irradiation?

BACKGROUND: Voluntary moderate deep inspiration breath-hold (vmDIBH) is widely used for left sided breast cancer patients. The purpose of this study was to investigate the usefulness of vmDIBH in local and locoregional radiation therapy (RT) of right-sided breast cancer. MATERIALS AND METHODS: For fourteen right-sided breast cancer patients, 3D-conformal (3D-CRT) RT plans (i.e., forward IMRT) were calculated on free-breathing (FB) 3D-CRT(FB) and vmDIBHCT-scans, for local- as well as locoregional breast treatment, with and without internal mammary nodes (IMN). Dose volume parameters were compared. RESULTS: For local breast treatment, no relevant reduction in mean lung dose (MLD) was found. For locoregional breast treatment without IMN, the average MLD reduced from 6.5 to 5.4 Gy (p < 0.005) for the total lung and from 11.2 to 9.7 Gy (p < 0.005) for the ipsilateral lung. For locoregional breast treatment with IMN, the average MLD reduced from 10.8 to 9.1 Gy (p < 0.005) for the total lung and from 18.7 to 16.2 Gy (p < 0.005) for the ipsilateral lung, whilea small reduction in mean heart dose of 0.4 Gy (p = 0.07) was also found. CONCLUSIONS: Breathing adapted radiation therapy in left-sided breast cancer patients is becoming widely introduced. As a result of the slight reduction in lung dose found for locoregional right-sided breast cancer treatment in this study, a slightly lower risk of pneumonitis and secondary lung cancer (in ever smoking patients) can be expected.In addition, for some patients the heart dose will also be reduced by more than 0.5 up to 2.6 Gy. We therefore suggest to also apply breath-hold for locoregional irradiation of right-sided breast cancer patients.

Identification of modes of tumor regression in non-small cell lung cancer patients during radiotherapy.

PURPOSE: Observed gross tumor volume (GTV) shrinkage during radiotherapy (RT) raises the question of whether to adapt treatment to changes observed on the acquired images. In the literature, two modes of tumor regression have been described: elastic and non-elastic. These modes of tumor regression will affect the safety of treatment adaptation. This study applies a novel approach, using routine cone-beam computed tomography (CBCT) and deformable image registration to automatically distinguish between elastic and non-elastic tumor regression. METHODS: In this retrospective study, 150 locally advanced non-small cell lung cancer patients treated with 55 Gray of radiotherapy were included. First, the two modes of tumor regression were simulated. For each mode of tumor regression, one timepoint was simulated. Based on the results of simulated data, the approach used for analysis in real patients was developed. CBCTs were non-rigidly registered to the baseline CBCT using a cubic B-spline algorithm, NiftyReg. Next, the Jacobian determinants were computed from the deformation vector fields. To capture local volume changes, 10 Jacobian values were sampled perpendicular to the surface of the GTV, across the lung-tumor boundary. From the simulated data, we can distinguish elastic from non-elastic tumor regression by comparing the Jacobian values samples between 5 and 12.5 mm inside and 5 and 12.5 mm outside the planning GTV. Finally, morphometric results were compared between tumors of different histologies. RESULTS: Most patients (92.3%) in our cohort showed stable disease in the first week of treatment and non-elastic shrinkage in the later weeks of treatment. At week 2, 125 patients (88%) showed stable disease, three patients (2.1%) disease progression, and 11 patients (8%) regression. By treatment completion, 91 patients (64%) had stable disease, one patient (0.7%) progression and 46 patients (32%) regression. A slight difference in the mode of tumor change was observed between tumors of different histologies. CONCLUSION: Our novel approach shows that it may be possible to automatically quantify and identify global changes in lung cancer patients during RT, using routine CBCT images. Our results show that different regions of the tumor change in different ways. Therefore, careful consideration should be taken when adapting RT.

Dose-Response Analysis Describes Particularly Rapid Repopulation of Non-Small Cell Lung Cancer during Concurrent Chemoradiotherapy.

(1) Purpose: We analysed overall survival (OS) rates following radiotherapy (RT) and chemo-RT of locally-advanced non-small cell lung cancer (LA-NSCLC) to investigate whether tumour repopulation varies with treatment-type, and to further characterise the low α/ß ratio found in a previous study. (2) Materials and methods: Our dataset comprised 2-year OS rates for 4866 NSCLC patients (90.5% stage IIIA/B) belonging to 51 cohorts treated with definitive RT, sequential chemo-RT (sCRT) or concurrent chemo-RT (cCRT) given in doses-per-fraction ≤3 Gy over 16-60 days. Progressively more detailed dose-response models were fitted, beginning with a probit model, adding chemotherapy effects and survival-limiting toxicity, and allowing tumour repopulation and α/ß to vary with treatment-type and stage. Models were fitted using the maximum-likelihood technique, then assessed via the Akaike information criterion and cross-validation. (3) Results: The most detailed model performed best, with repopulation offsetting 1.47 Gy/day (95% confidence interval, CI: 0.36, 2.57 Gy/day) for cCRT but only 0.30 Gy/day (95% CI: 0.18, 0.47 Gy/day) for RT/sCRT. The overall fitted tumour α/ß ratio was 3.0 Gy (95% CI: 1.6, 5.6 Gy). (4) Conclusion: The fitted repopulation rates indicate that cCRT schedule durations should be shortened to the minimum in which prescribed doses can be tolerated. The low α/ß ratio suggests hypofractionation should be efficacious.

Early prediction of tumour-response to radiotherapy in NSCLC patients.

Objective. In this study we developed an automatic method to predict tumour volume and shape in weeks 3 and 4 of radiotherapy (RT), using cone-beam computed tomography (CBCT) scans acquired up to week 2, allowing identification of large tumour changes.Approach. 240 non-small cell lung cancer (NSCLC) patients, treated with 55 Gy in 20 fractions, were collected. CBCTs were rigidly registered to the planning CT. Intensity values were extracted in each voxel of the planning target volume across all CBCT images from days 1, 2, 3, 7 and 14. For each patient and in each voxel, four regression models were fitted to voxel intensity; applying linear, Gaussian, quadratic and cubic methods. These models predicted the intensity value for each voxel in weeks 3 and 4, and the tumour volume found by thresholding. Each model was evaluated by computing the root mean square error in pixel value and structural similarity index metric (SSIM) for all patients. Finally, the sensitivity and specificity to predict a 30% change in volume were calculated for each model.Main results. The linear, Gaussian, quadratic and cubic models achieved a comparable similarity score, the average SSIM for all patients was 0.94, 0.94, 0.90, 0.83 in week 3, respectively. At week 3, a sensitivity of 84%, 53%, 90% and 88%, and specificity of 99%, 100%, 91% and 42% were observed for the linear, Gaussian, quadratic and cubic models respectively. Overall, the linear model performed best at predicting those patients that will benefit from RT adaptation. The linear model identified 21% and 23% of patients in our cohort with more than 30% tumour volume reduction to benefit from treatment adaptation in weeks 3 and 4 respectively.Significance. We have shown that it is feasible to predict the shape and volume of NSCLC tumours from routine CBCTs and effectively identify patients who will respond to treatment early.

Outcomes of curative-intent radiotherapy in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).

Outcomes of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD n = 587) and interstitial lung disease (ILD n = 34) treated with curative-intent radiotherapy were retrospectively investigated. Presence of ILD but not decreased forced expiratory volume in 1-second correlated with poor overall survival. Increased breathlessness and oxygen requirements after radiotherapy were observed in severe/very severe COPD and ILD.

MRI and CBCT for lymph node identification and registration in patients with NSCLC undergoing radical radiotherapy.

PURPOSE: This study compared MRI to CBCT for the identification and registration of lymph nodes (LN) in patients with locally advanced (LA)-NSCLC, to assess the suitability of targeting LNs in future MR-image guided radiotherapy (MRgRT) workflows. METHOD: Radiotherapy radiographers carried out Visual Grading Analysis (VGA) assessment of image quality, LN registration and graded their confidence in registration for each of the 24 LNs on CBCT and two MR sequences, MR1 (T2w Turbo Spin Echo) and MR2 (T1w DIXON water only image). RESULTS: Pre-registration image quality assessment revealed MR1 and MR2 as significantly superior to CBCT in terms of image quality (p ≤ 0.01). No significant differences were noted in interobserver variability for LN registration between CBCT, MR1 and MR2. Observers were more confident in their MR registrations compared to their CBCT based LN registrations (p ≤ 0.02). SUMMARY: Interobserver setup correction variability was not found to be significantly different between CBCT and MR. Image quality and registration confidence were found to be superior for MRI sequences. This is a promising step towards MR-guided radiotherapy for the treatment of LA-NSCLC.

Initial Clinical Experience of MR-Guided Radiotherapy for Non-Small Cell Lung Cancer.

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and Elekta Unity. The challenges and potential solutions associated with MRgRT in lung cancer will also be highlighted.

Identification of patterns of tumour change measured on CBCT images in NSCLC patients during radiotherapy.

In this study, we propose a novel approach to investigate changes in the visible tumour and surrounding tissues with the aim of identifying patterns of tumour change during radiotherapy (RT) without segmentation on the follow-up images. On-treatment cone-beam computed tomography (CBCT) images of 240 non-small cell lung cancer (NSCLC) patients who received 55 Gy of RT were included. CBCTs were automatically aligned onto planning computed tomography (planning CT) scan using a two-step rigid registration process. To explore density changes across the lung-tumour boundary, eight shells confined to the shape of the gross tumour volume (GTV) were created. The shells extended 6 mm inside and outside of the GTV border, and each shell is 1.5 mm thick. After applying intensity correction on CBCTs, the mean intensity was extracted from each shell across all CBCTs. Thereafter, linear fits were created, indicating density change over time in each shell during treatment. The slopes of all eight shells were clustered to explore patterns in the slopes that show how tumours change. Seven clusters were obtained, 97% of the patients were clustered into three groups. After visual inspection, we found that these clusters represented patients with little or no density change, progression and regression. For the three groups, the survival curves were not significantly different between the groups, p-value = 0.51. However, the results show that definite patterns of tumour change exist, suggesting that it may be possible to identify patterns of tumour changes from on-treatment CBCT images.

Looking through the eyes of the multidisciplinary team: the design and clinical evaluation of a decision support system for lung cancer care.

BACKGROUND: Decision-making in lung cancer is complex due to a rapidly increasing amount of diagnostic data and treatment options. The need for timely and accurate diagnosis and delivery of care demands high-quality multidisciplinary team (MDT) collaboration and coordination. Clinical decision support systems (CDSSs) can potentially support MDTs in constructing a shared mental model of a patient case. This enables the team to assess the strength and completeness of collected diagnostic data, stratification for the right personalized therapy driven by clinical stage and other treatment-influencing factors, and adapt care management strategies when needed. Current CDSSs often have a suboptimal fit into the decision-making workflow, which hampers their impact in clinical practice. METHODS: A CDSS for multidisciplinary decision-making in lung cancer was designed to support the abovementioned goals through presentation of relevant clinical data in line with existing mental model structures of the MDT members. The CDSS was tested in a simulated multidisciplinary tumor board meeting for primary diagnosis and treatment selection, based on de-identified primary lung cancer cases (n=8). Decision course analysis, eye-tracking data and questionnaires were used to assess the impact of the CDSS on constructing shared mental models to improve the decision-making process and outcome. RESULTS: The CDSS supported the team in their self-correcting capacity for accurate diagnosis and TNM classification. It enabled cross-validation of diagnostic findings, surfaced discordance between diagnostic tests and facilitated cancer staging according the diagnostic evidence, as well as spotting contra-indications for personalized treatment selection. CONCLUSIONS: This study shows the potential of CDSS on clinical decision making, when these systems are properly designed in line with clinical thinking. The presented setup enables assessment of the impact of CDSS design on clinical decision making and optimization of CDSSs to maximize their effect on decision quality and confidence.

Protecting the Heart: A Practical Approach to Account for the Full Extent of Heart Motion in Radiation Therapy Planning.

PURPOSE: Emerging evidence suggests that the heart is more radiosensitive than previously assumed; therefore, accounting for heart motion in radiation therapy planning is becoming more critical. In this study, we determined how much heart delineations based on 3-dimensional (3D) computed tomography (CT), 4-dimensional (4D) average projection (AVG), and maximum intensity projection (MIP) images should be extended to represent the full extent of heart motion during 4D imaging acquisition. METHODS AND MATERIALS: The 3D and 4D CT scans of 10 lung cancer patients treated with stereotactic ablative radiation therapy were used. Median surfaces were derived from heart delineations of 3 observers on the 3D CT, AVG, MIP, and 25% exhale scans. Per patient, the 25% exhale contour was propagated on every phase of the 4D scan. The union of all 4D phase delineations (U4D) represented the full extent of heart motion during imaging acquisition. Surface distances from U4D to 3D, AVG, and MIP volumes were calculated. Distances in the most extreme surface points (1.5 cm most superoinferior, 10% most right/left/anteroposterior) were used to derive margins accounting only for systematic (delineation) errors. RESULTS: Heart delineations on the MIP were the closest to the full extent of motion, requiring only ≤2.5-mm margins. Delineations on the AVG and 3D scans required margins up to 3.4 and 7.1 mm, respectively. The largest margins were for the inferior, right, and anterior aspects for the delineations on the 3D, AVG, and MIP scans, respectively. CONCLUSION: Delineations on 3D, AVG, or MIP scans required extensions for representing the heart's full extent of motion, with the MIP requiring the smallest margins. Research including daily imaging to determine the random components for the margins and dosimetric measurements to determine the relevance of creating a planning organ at risk volume of the heart is required.

Comparison between Conventional IMRT Planning and a Novel Real-Time Adaptive Planning Strategy in Hypofractionated Regimes for Prostate Cancer: A Proof-of-Concept Planning Study.

In prostate cancer external beam radiation therapy (EBRT), intra-fraction prostate drifts may compromise the treatment efficacy by underdosing the target and/or overdosing the organs at risk. In this study, a recently developed real-time adaptive planning strategy for intensity-modulated radiation therapy (IMRT) for prostate cancer was evaluated in hypofractionated regimes against traditional treatment planning based on a treatment volume margin expansion. The proposed workflow makes use of a "library of plans" corresponding to possible intra-fraction prostate positions. During delivery, at each beam end, the plan prepared for the position of the prostate closest to the current one is selected and the corresponding beam delivered. This adaptive planning strategy was compared with the traditional approach on a clinical prostate cancer case where different prostate shift magnitudes were considered. Five, six and fifteen fraction hypofractionated schemes were considered for each of these scenarios. When shifts larger than the treatment margin were present, using the traditional approach the seminal vesicles were underdosed by 3-4% of the prescribed dose. The adaptive approach instead allowed for correct target dose coverage and lowered the dose on the rectum for each dosimetric endpoint on average by 3-4% in all the fractionation schemes. Standard intensity-modulated radiation therapy planning did not always guarantee a correct dose distribution on the seminal vesicles and the rectum. The adaptive planning strategy proposed resulted insensitive to the intra-fraction prostate drifts, produced a dose distribution in agreement with the dosimetric requirements in every case analysed and significantly lowered the dose on the rectum.

Real-time adaptive planning method for radiotherapy treatment delivery for prostate cancer patients, based on a library of plans accounting for possible anatomy configuration changes.

BACKGROUND AND PURPOSE: In prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one. MATERIAL AND METHODS: Our adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A "library" of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed. RESULTS: For the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved. CONCLUSIONS: In our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level.

Emerging Role of MRI for Radiation Treatment Planning in Lung Cancer.

Magnetic resonance imaging (MRI) provides excellent soft-tissue contrast and allows for specific scanning sequences to optimize differentiation between various tissue types and properties. Moreover, it offers the potential for real-time motion imaging. This makes magnetic resonance imaging an ideal candidate imaging modality for radiation treatment planning in lung cancer. Although the number of clinical research protocols for the application of magnetic resonance imaging for lung cancer treatment is increasing (www.clinicaltrials.gov) and the magnetic resonance imaging sequences are becoming faster, there are still some technical challenges. This review describes the opportunities and challenges of magnetic resonance imaging for radiation treatment planning in lung cancer.

Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.

UNLABELLED: 18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated. METHODS: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. RESULTS: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis. CONCLUSION: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.

Detection and grading of soft tissue sarcomas of the extremities with (18)F-3'-fluoro-3'-deoxy-L-thymidine.

PURPOSE: The aim of the study was to investigate the feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS). EXPERIMENTAL DESIGN: Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems. RESULTS: Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (* = 0.550-0.747). CONCLUSIONS: FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.

Is 18F-3'-fluoro-3'-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer?

UNLABELLED: The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC underwent whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of 18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420 MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET was performed 60 min after 18F-FLT injection. Two viewers independently categorized the localization and intensity of tracer uptake for all lesions. All 18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was compared with clinical TNM staging based on the findings of history, physical examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated. RESULTS: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was 80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the 9 patients who did not receive pretreatment, using 18F-FDG PET as the reference standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of 8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET, at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F-FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range of 2.8-13.9 (n = 6; P = 0.027). CONCLUSION: 18F-FLT PET is not useful for staging and restaging NSCLC.

3'-18F-fluoro-3'-deoxy-L-thymidine: a new tracer for staging metastatic melanoma?

UNLABELLED: In this study, the feasibility of 3'-(18)F-fluoro-3'-deoxy-L-thymidine PET ((18)F-FLT PET) for staging patients with clinical stage III melanoma was investigated. METHODS: Ten patients with melanoma and metastases to the locoregional draining lymph nodes, clinical stage III-based on physical examination, chest radiography, lactate dehydrogenase, and histopathologic confirmation-underwent a whole-body (18)F-FLT PET scan 1 h after injection of a median 400-MBq dose (range, 185-430 MBq) of (18)F-FLT. All (18)F-FLT PET lesions were verified using the American Joint Committee on Cancer Staging System, which includes physical examination, spiral CT, ultrasound, chest radiography, and histopathologic examinations. Size and mitotic rate of metastatic lymph nodes and skin metastases were determined. RESULTS: All histopathologic samples and (18)F-FLT PET lesions were categorized over anatomic regions and correlated. All locoregional metastases were correctly visualized by (18)F-FLT PET. Region-based sensitivity for detection of lymph node metastatic disease was 88%. There were 3 true-negative and 2 false-positive lesions. The detection limit for lymph node metastases appeared to be approximately 6 mm or a mitotic rate of 9 mitoses per 2 mm(2). Two patients were upstaged by (18)F-FLT PET, which was confirmed by CT. In 3 patients, (18)F-FLT PET detected a total of 3 additional lesions with therapeutic consequences, without influencing staging. These lesions were initially missed by clinical staging. CONCLUSION: (18)F-FLT PET seems promising for (re)staging purposes in clinical stage III melanoma. Further research is needed, in which (18)F-FLT PET should be compared with (18)F-FDG PET.

18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET.

UNLABELLED: The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with (18)F-FDG PET. METHODS: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation-corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F-FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT PET. Two-tailed P values < 0.05 were considered significant. RESULTS: (18)F-FDG PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients. One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of 2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7 (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P < 0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for (18)F-FLT (P < 0.05). CONCLUSION: The numbers of laryngeal cancers detected with (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of (18)F-FDG is higher than that of (18)F-FLT.