Wiviann Ottosson

Adaptation requirements due to anatomical changes in free-breathing and deep-inspiration breath-hold for standard and dose-escalated radiotherapy of lung cancer patients

ABSTRACT Background. Radiotherapy of lung cancer patients is subject to uncertainties related to heterogeneities, anatomical changes and breathing motion. Use of deep-inspiration breath-hold (DIBH) can reduce the treated volume, potentially enabling dose-escalated (DE) treatments. This study was designed to investigate the need for adaptation due to anatomical changes, for both standard (ST) and DE plans in free-breathing (FB) and DIBH. Material and methods. The effect of tumor shrinkage (TS), pleural effusion (PE) and atelectasis was investigated for patients and for a CIRS thorax phantom. Sixteen patients were computed tomography (CT) imaged both in FB and DIBH. Anatomical changes were simulated by CT information editing and re-calculations, of both ST and DE plans, in the treatment planning system. PE was systematically simulated by adding fluid in the dorsal region of the lung and TS by reduction of the tumor volume. Results. Phantom simulations resulted in maximum deviations in mean dose to the GTV-T (GTV-T) of −1% for 3 cm PE and centrally located tumor, and + 3% for TS from 5 cm to 1 cm diameter for an anterior tumor location. For the majority of the patients, simulated PE resulted in a decreasing GTV-T with increasing amount of fluid and increasing GTV-T for decreasing tumor volume. Maximum change in GTV-T of -3% (3 cm PE in FB for both ST and DE plans) and + 10% (2 cm TS in FB for DE plan) was observed. Large atelectasis reduction increased the GTV-T with 2% for FB and had no effect for DIBH. Conclusion. Phantom simulations provided potential adaptation action levels for PE and TS. For the more complex patient geometry, individual assessment of the dosimetric impact is recommended for both ST and DE plans in DIBH as well as in FB. However, DIBH was found to be superior over FB for DE plans, regarding robustness of GTV-T to TS.

Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study

BACKGROUND AND PURPOSE Local recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose-escalation driven by FDG-avid volumes, while respecting normal tissue constraints and requiring no increase in mean lung dose. Dose-escalation driven by FDG-avid volumes, delivering mean doses of 95Gy (tumour) and 74Gy (lymph nodes), was pursued and compared to standard 66Gy/33F plans. MATERIAL AND METHODS Dose plans for the first thirty patients enroled were analysed. Standard and escalated plans were created for all patients, blinded to randomization, and compared for each patient in terms of the ability to escalate while protecting normal tissue. RESULTS The median dose-escalation in FDG-avid areas was 93.9Gy (tumour) and 73.0Gy (lymph nodes). Escalation drove the GTV and CTV to mean doses for the tumour of 87.5Gy (GTV-T) and 81.3Gy (CTV-T) in median. No significant differences in mean dose to lung and heart between standard and escalated were found, but small volumes of e.g. the bronchi received doses between 66 and 74Gy due to escalation. CONCLUSIONS FDG-driven inhomogeneous dose-escalation achieves large increment in tumour and lymph node dose, while delivering similar doses to normal tissue as homogenous standard plans.

Deformable image registration for geometrical evaluation of DIBH radiotherapy treatment of lung cancer patients

Respiration and anatomical variation during radiotherapy (RT) of lung cancer yield dosimetric uncertainties of the delivered dose, possibly affecting the clinical outcome if not corrected for. Adaptive radiotherapy (ART), based on deformable image registration (DIR) and Deep-Inspiration-Breath-Hold (DIBH) gating can potentially improve the accuracy of RT. Purpose: The objective was to investigate the performance of contour propagation on repeated CT and Cone Beam CT (CBCT) images in DIBH compared to images acquired in free breathing (FB), using a recently released DIR software. Method: Three locally advanced non-small cell lung cancer patients were included, each with a planning-, midterm- and final CT (pCT, mCT, fCT) and 7 CBCTs acquired weekly and on the same day as the mCT and fCT. All imaging were performed in both FB and DIBH, using Varian RPM system for respiratory tracking. Delineations of anatomical structures were performed on each image set. The CT images were retrospective rigidly and deformable registered to all obtained images using the Varian Smart Adapt v. 11.0. The registered images were analysed for volume change and Dice Similarity Coefficient (DSC). Result: Geometrical similarities were found between propagated and manually delineated structures, with a slightly favour of FB imaging. Special notice should be taken to registrations where image artefacts or low tissue contrast are present. Conclusion: This study does not support the hypothesis that DIBH images perform better image registration than FB images. However DIR is a feasible tool for ART of lung cancer.

The advantage of deep-inspiration breath-hold and cone-beam CT based soft-tissue registration for locally advanced lung cancer radiotherapy

BACKGROUND AND PURPOSE Three cone-beam computed tomography (CBCT) registration strategies combined with deep-inspiration breath-hold (DIBH) and free-breathing (FB) were explored, in terms of obtaining the smallest planning target volume (PTV). MATERIAL AND METHODS CBCT images were acquired pre- and post-treatment in FB and DIBH, for 17 locally advanced lung cancer patients. Bony registration on the spine, and soft-tissue registrations on the primary gross tumor volume (GTV-T) and GTV-Total, including malignant lymph nodes (GTV-N), were retrospectively analyzed. Setup-margins and resulting PTVs were calculated. RESULTS For the spine, the smallest residual misalignments were observed in FB, independently of registration method. For GTV-T and GTV-N, soft-tissue registrations were superior to bony registration, independently of FB or DIBH. Compared to FB, PTV-Totals were during DIBH reduced by 13% and 8% for the soft-tissue and bony registrations, respectively. If intra-fractional motion was included, the corresponding gain of DIBH was reduced to 9% and 7%, respectively. Superiority of DIBH was mainly due to larger clinical target volumes in FB. CONCLUSIONS Despite larger setup uncertainties compared to FB, DIBH resulted in smaller PTV-Totals for all registration methods. Soft-tissue registrations were superior to bony registration, independently of FB and DIBH. During DIBH, undesirable arching of the back was identified. Daily CBCT pre-treatment target verification is advised.

Monte Carlo calculations support organ sparing in Deep-Inspiration Breath-Hold intensity-modulated radiotherapy for locally advanced lung cancer

BACKGROUND AND PURPOSE Studies indicate that Deep-Inspiration Breath-Hold (DIBH) is advantageous over Free-Breathing (FB) for locally advanced lung cancer radiotherapy. However, these studies were based on simplified dose calculation algorithms, potentially critical due to the heterogeneous nature of the lung region. Using detailed Monte-Carlo (MC) calculations, a comparative study of DIBH vs. FB was therefore designed. MATERIAL AND METHODS Eighteen locally advanced lung cancer patients underwent FB and DIBH CT imaging and treatment planning with the Anisotropic-Analytical-Algorithm (AAA) for intensity-modulated-radiotherapy or volumetric-modulated-arc-therapy using 66Gy in 33 fractions. All plans were re-calculated with MC. RESULTS Relative to FB, the total lung volume increased 86.8% in DIBH, while the gross tumor volume decreased 14.8%. MC revealed equally under- and over-dosage of the target for FB and DIBH, compared to AAA. For the Organs-At-Risk (OARs), DIBH reduced the mean heart dose by 25.5% (AAA) vs. 12.6% (MC), the total lung V5Gy/V20Gy by 9.0/20.0% (AAA) vs. 11.6/19.9% (MC). CONCLUSIONS MC calculations revealed (i) that DIBH compared with FB can significantly reduce the dose to the OARs even if the treatment planning is carried out with AAA, and (ii) inferior target dose coverage compared to AAA, irrespectively of FB and DIBH. The dose deviations were similar for FB and DIBH. The observed inferior target dose coverage relates therefore to the treatment planning algorithm rather than breathing technique.

Dose verification of radiotherapy for lung cancer by using plastic scintillator dosimetry and a heterogeneous phantom

Bone, air passages, cavities, and lung are elements present in patients, but challenging to properly correct for in treatment planning dose calculations. Plastic scintillator detectors (PSDs) have proven to be well suited for dosimetry in non-reference conditions such as small fields. The objective of this study was to investigate the performance of a commercial treatment planning system (TPS) using a PSD and a specially designed thorax phantom with lung tumor inserts. 10 treatment plans of different complexity and phantom configurations were evaluated. Although the TPS agreed well with the measurements for the least complex tests, deviations of tumor dose > 4% were observed for some cases. This study underpins the dosimetric challenge in TPS calculations for clinically relevant heterogeneous geometries. The scintillator system, together with the special phantom, provides a promising tool for evaluation of complex radiotherapy dose calculations and delivery.