Deep inspiration breath hold in locally advanced lung cancer radiotherapy: validation of intrafractional geometric uncertainties in the INHALE trial.

OBJECTIVES: Patients with locally advanced non-small cell lung cancer (NSCLC) were included in a prospective trial for radiotherapy in deep inspiration breath hold (DIBH). We evaluated DIBH compliance and target position reproducibility. METHODS: Voluntary, visually guided DIBHs were performed with optical tracking. Patients underwent three consecutive DIBH CT scans for radiotherapy planning. We evaluated the intrafractional uncertainties in the position of the peripheral tumour, lymph nodes and differential motion between them, enabling PTV margins calculation. Patients who underwent all DIBH imaging and had tumour position reproducibility <8 mm were up-front DIBH compliant. Patients who performed DIBHs throughout the treatment course were overall DIBH compliant. Clinical parameters and DIBH-related uncertainties were validated against our earlier pilot study. RESULTS: 69 of 88 included patients received definitive radiotherapy. 60/69 patients (87%) were up-front DIBH compliant. DIBH plan was not superior in seven patients and three lost DIBH ability during the treatment, leaving 50/69 patients (72%) overall DIBH compliant.The systematic and random errors between consecutive DIBHs were small but differed from the pilot study findings. This led to slightly different PTV margins between the two studies. CONCLUSIONS: DIBH compliance and reproducibility was high. Still, this validation study highlighted the necessity of designing PTV margins in larger, representative patient cohorts. ADVANCES IN KNOWLEDGE: We demonstrated high DIBH compliance in locally advanced NSCLC patients. DIBH does not eliminate but mitigates the target position uncertainty, which needs to be accounted for in treatment margins. Margin design should be based on data from larger representative patient groups.

A modeling study of functional magnetic resonance imaging to individualize target definition of seminal vesicles for external beam radiotherapy.

BACKGROUND: Pre-treatment magnetic resonance imaging (MRI) can give patient-specific evaluation of suspected pathologically involved volumes in the seminal vesicles (SV) in prostate cancer patients. By targeting this suspicious volume we hypothesize that radiotherapy is more efficient without introducing more toxicity. In this study we evaluate the concept of using MRI-defined target volumes in terms of tumor control probability (TCP) and rectal normal tissue complication probability (NTCP). MATERIAL AND METHODS: Twenty-one high-risk prostate cancer patients were included. Pre-treatment CT images, T2 weighted (T2w) MRI and two multi-parametric MRI were acquired. Overlap between a suspicious volume in the SV observed on T2w images and a suspicious volume observed on either multi-parametric MRI was assumed to reflect a true malignant region (named 'MRI positive'). In addition the entire SV on the CT-scan was delineated. Three treatment plans of 2 Gy ×39 fractions were generated per patient: one covering the MRI positive volume in SV and prostate with margin of 11 mm to the MRI positive in the SV and two plans covering prostate and SV using 11 and 7 mm SV margin, respectively. All plans were prescribed the same PTV mean dose. Rectal NTCP grade ≥2 was evaluated with the Lyman-Kutcher-Burman model and TCP was estimated by a logistic model using the combined MRI positive volume in SV and prostate as region-of-interest. RESULTS: Fourteen of twenty-one patients were classified as MRI positive, six of which had suspicious volumes in all three MRI modalities. On average TCP for the plan covering prostate and the MRI positive volume was 3% higher (up to 11%) than the two other plans which was statistically significant. The increased TCP was obtained without increasing rectal NTCP grade ≥2. CONCLUSIONS: Using functional MRI for individualized target delineation in the SV may improve the treatment outcome in radiotherapy of prostate cancer without increasing the rectal toxicity.

Megavoltage image-based dynamic multileaf collimator tracking of a NiTi stent in porcine lungs on a linear accelerator.

PURPOSE: To investigate the accuracy and potential limitations of MV image-based dynamic multileaf collimator (DMLC) tracking in a porcine model on a linear accelerator. METHODS AND MATERIALS: A thermo-expandable NiTi stent designed for kilovoltage (kV) X-ray visualization of lung lesions was inserted into the bronchia of three anaesthetized Göttingen minipigs. A four-dimensional computed tomography scan was used for planning a five-field conformal treatment with circular multileaf collimator (MLC) apertures. A 22.5 Gy single fraction treatment was delivered to the pigs. The peak-to-peak stent motion was 3 to 8 mm, with breathing periods of 1.2 to 4 s. Before treatment, X-ray images were used for image-guided setup based on the stent. During treatment delivery, continuous megavoltage (MV) portal images were acquired at 7.5 Hz. The stent was segmented in the images and used for continuous adaptation of the MLC aperture. Offline, the tracking error in beam's eye view of the treatment beam was calculated for each MV image as the difference between the MLC aperture center and the segmented stent position. The standard deviations of the systematic error Σ and the random error σ were determined and compared with the would-be errors for a nontracking treatment with pretreatment image-guided setup. RESULTS: Reliable stent segmentation was obtained for 11 of 15 fields. Segmentation failures occurred when image contrast was dominated by overlapping anatomical structures (ribs, diaphragm) rather than by the stent, which was designed for kV rather than MV X-ray visibility. For the 11 fields with reliable segmentation, Σ was 0.5 mm/0.4 mm in the two imager directions, whereas σ was 0.5 mm/1.1 mm. Without tracking, Σ and σ would have been 1.7 mm/1.4 mm and 0.8 mm/1.4 mm, respectively. CONCLUSION: For the first time, in vivo DMLC tracking has been demonstrated on a linear accelerator showing the potential for improved targeting accuracy. The study mimicked the envisioned patient workflow of future patient treatments. Clinical implementation of MV image-based tracking would require markers designed for MV visibility.

Assessment of optical coherence tomography imaging in the diagnosis of non-melanoma skin cancer and benign lesions versus normal skin: observer-blinded evaluation by dermatologists and pathologists.

BACKGROUND: Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES: To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess the diagnostic accuracy of OCT in differentiating NMSC from benign lesions and normal skin. METHODS AND MATERIALS: OCT and polarization-sensitive (PS) OCT from 104 patients were studied. Observer-blinded evaluation of OCT images from 64 BCCs, 1 baso-squamous carcinoma, 39 AKs, two malignant melanomas, nine benign lesions, and 105 OCT images from perilesional skin was performed; 50 OCT images of NMSC and 50 PS-OCT images of normal skin were evaluated twice. RESULTS: Sensitivity was 79% to 94% and specificity 85% to 96% in differentiating normal skin from lesions. Important features were absence of well-defined layering in OCT and PS-OCT images and dark lobules in BCC. Discrimination of AK from BCC had an error rate of 50% to 52%. CONCLUSION: OCT features in NMSC are identified, but AK and BCC cannot be differentiated. OCT diagnosis is less accurate than clinical diagnosis, but high accuracy in distinguishing lesions from normal skin, crucial for delineating tumor borders, was obtained.