Sarah O.S. Osman

Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation.

PURPOSE To investigate the effects of using volumetric modulated arc therapy (VMAT) and/or voluntary moderate deep inspiration breath-hold (vmDIBH) in the radiation therapy (RT) of left-sided breast cancer including the regional lymph nodes. MATERIALS AND METHODS For 13 patients, four treatment combinations were compared; 3D-conformal RT (i.e., forward IMRT) in free-breathing 3D-CRT(FB), 3D-CRT(vmDIBH), 2 partial arcs VMAT(FB), and VMAT(vmDIBH). Prescribed dose was 42.56 Gy in 16 fractions. For 10 additional patients, 3D-CRT and VMAT in vmDIBH only were also compared. RESULTS Dose conformity, PTV coverage, ipsilateral and total lung doses were significantly better for VMAT plans compared to 3D-CRT. Mean heart dose (D(mean,heart)) reduction in 3D-CRT(vmDIBH) was between 0.9 and 8.6 Gy, depending on initial D(mean,heart) (in 3D-CRT(FB) plans). VMAT(vmDIBH) reduced the D(mean,heart) further when D(mean,heart) was still >3.2 Gy in 3D-CRT(vmDIBH). Mean contralateral breast dose was higher for VMAT plans (2.7 Gy) compared to 3DCRT plans (0.7 Gy). CONCLUSIONS VMAT and 3D-CRT(vmDIBH) significantly reduced heart dose for patients treated with locoregional RT of left-sided breast cancer. When Dmean,heart exceeded 3.2 Gy in 3D-CRT(vmDIBH) plans, VMAT(vmDIBH) resulted in a cumulative heart dose reduction. VMAT also provided better target coverage and reduced ipsilateral lung dose, at the expense of a small increase in the dose to the contralateral breast.

IMRT for image-guided single vocal cord irradiation

PURPOSE We have been developing an image-guided single vocal cord irradiation technique to treat patients with stage T1a glottic carcinoma. In the present study, we compared the dose coverage to the affected vocal cord and the dose delivered to the organs at risk using conventional, intensity-modulated radiotherapy (IMRT) coplanar, and IMRT non-coplanar techniques. METHODS AND MATERIALS For 10 patients, conventional treatment plans using two laterally opposed wedged 6-MV photon beams were calculated in XiO (Elekta-CMS treatment planning system). An in-house IMRT/beam angle optimization algorithm was used to obtain the coplanar and non-coplanar optimized beam angles. Using these angles, the IMRT plans were generated in Monaco (IMRT treatment planning system, Elekta-CMS) with the implemented Monte Carlo dose calculation algorithm. The organs at risk included the contralateral vocal cord, arytenoids, swallowing muscles, carotid arteries, and spinal cord. The prescription dose was 66 Gy in 33 fractions. RESULTS For the conventional plans and coplanar and non-coplanar IMRT plans, the population-averaged mean dose ± standard deviation to the planning target volume was 67 ± 1 Gy. The contralateral vocal cord dose was reduced from 66 ± 1 Gy in the conventional plans to 39 ± 8 Gy and 36 ± 6 Gy in the coplanar and non-coplanar IMRT plans, respectively. IMRT consistently reduced the doses to the other organs at risk. CONCLUSIONS Single vocal cord irradiation with IMRT resulted in good target coverage and provided significant sparing of the critical structures. This has the potential to improve the quality-of-life outcomes after RT and maintain the same local control rates.

On-line cone beam CT image guidance for vocal cord tumor targeting☆

BACKGROUND AND PURPOSE We are developing a technique for highly focused vocal cord irradiation in early glottic carcinoma to optimally treat a target volume confined to a single cord. This technique, in contrast with the conventional methods, aims at sparing the healthy vocal cord. As such a technique requires sub-mm daily targeting accuracy to be effective, we investigate the accuracy achievable with on-line kV-cone beam CT (CBCT) corrections. MATERIALS AND METHODS CBCT scans were obtained in 10 early glottic cancer patients in each treatment fraction. The grey value registration available in X-ray volume imaging (XVI) software (Elekta, Synergy) was applied to a volume of interest encompassing the thyroid cartilage. After application of the thus derived corrections, residue displacements with respect to the planning CT scan were measured at clearly identifiable relevant landmarks. The intra- and inter-observer variations were also measured. RESULTS While before correction the systematic displacements of the vocal cords were as large as 2.4+/-3.3mm (cranial-caudal population mean+/-SD Sigma), daily CBCT registration and correction reduced these values to less than 0.2+/-0.5mm in all directions. Random positioning errors (SD sigma) were reduced to less than 1mm. Correcting only for translations and not for rotations did not appreciably affect this accuracy. The residue random displacements partly stem from intra-observer variations (SD=0.2-0.6mm). CONCLUSION The use of CBCT for daily image guidance in combination with standard mask fixation reduced systematic and random set-up errors of the vocal cords to <1mm prior to the delivery of each fraction dose. Thus, this facilitates the high targeting precision required for a single vocal cord irradiation.

Single vocal cord irradiation: A competitive treatment strategy in early glottic cancer

INTRODUCTION The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI). MATERIAL AND METHODS The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed. RESULTS A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved. CONCLUSIONS Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery.

Four-dimensional CT analysis of vocal cords mobility for highly focused single vocal cord irradiation

BACKGROUND AND PURPOSE To quantify respiratory motion of the vocal cords during normal respiration using 4D-CT. The final goal is to develop a technique for single vocal cord irradiation (SVCI) in early glottic carcinoma. Sparing the non-involved cord and surrounding structures has the potential to preserve voice quality and allow re-irradiation of recurrent and second primary tumors. MATERIAL AND METHODS Four-dimensional CTs of 1mm slice thickness from 10 early glottic carcinoma patients were acquired. The lateral dimensions of the air gap separating the vocal cords were measured anteriorly, at mid-level and posteriorly at each phase of the 4D-CTs. The corresponding anterior-posterior gaps were similarly measured. Cranio-caudal vocal cords movements during breathing were derived from the shifts of the arythenoids. RESULTS The population-averaged mean gap size+/-the corresponding standard deviation due to breathing (SD(B)) for the lateral gaps was 5.8+/-0.7mm anteriorly, 8.7+/-0.9mm at mid-level, and 11.0+/-1.3mm posteriorly. Anterior-posterior gap values were 21.7+/-0.7mm, while cranio-caudal shift SD(B) was 0.8mm. CONCLUSION Vocal cords breathing motions were found to be small relative to their separation. Hence, breathing motion does not seem to be a limiting factor for SVCI.

Accelerated partial breast irradiation (APBI): Are breath-hold and volumetric radiation therapy techniques useful?

Abstract Background. In a selective group of patients accelerated partial breast irradiation (APBI) might be applied after conservative breast surgery to reduce the amount of irradiated healthy tissue. The role of volumetric modulated arc therapy (VMAT) and voluntary moderately deep inspiration breath-hold (vmDIBH) techniques in further reducing irradiated healthy – especially heart – tissue is investigated. Material and methods. For 37 partial breast planning target volumes (PTVs), three-dimensional conformal radiotherapy (3D-CRT) (3–5 coplanar or non-coplanar 6 and/or 10 MV beams) and VMAT (two partial 6 MV arcs) plans were made on CTs acquired in free-breathing (FB) and/or in vmDIBH. Dose-volume parameters for the PTV, heart, lungs, and breasts were compared. Results. Better dose conformity was achieved with VMAT compared to 3D-CRT (conformity index 1.24 ± 0.09 vs. 1.49 ± 0.20). Non-PTV ipsilateral breast receiving ≥ 50% of the prescribed dose was on average reduced by 28% in VMAT plans compared to 3D-CRT plans. Mean heart dose (MHD) reduced from 2.0 (0.1–5.1) Gy in 3D-CRT(FB) to 0.6 (0.1–1.6) Gy in VMAT(vmDIBH). VMAT is beneficial for MHD reduction if MHD with 3D-CRT exceeds 0.5Gy. Cardiac dose reduction as a result of VMAT increases with increasing initial MHD, and adding vmDIBH reduces the cardiac dose further. Mean dose to the ipsilateral lung decreased from 3.7 (0.7–8.7) to 1.8 (0.5–4.0) Gy with VMAT(vmDIBH) compared to 3D-CRT(FB). VMAT resulted in a slight increase in the contralateral breast dose (DMean) always remaining < 1.9 Gy). Conclusions. For APBI patients, VMAT improves PTV dose conformity and delivers lower doses to the ipsilateral breast and lung compared to 3D-CRT. This goes at the cost of a slight but acceptable increase of the contralateral breast dose. VMAT reduces cardiac dose if MHD exceeds 0.5 Gy for 3D-CRT. Adding vmDIBH results in a further reduction of heart and ipsilateral lung dose.

Impact of geometric variations on delivered dose in highly focused single vocal cord IMRT

Abstract Purpose. To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. Material and methods. Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. Results. Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by −0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and −1.0 ± 9.6%, respectively. Conclusions. On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol.

IMRT IN IMAGE-GUIDED SINGLE VOCAL CORD IRRADIATION

Purpose: We have been developing an image-guided single vocal cord irradiation technique to treat patients with stage T1a glottic carcinoma. Inthe present study, we comparedthe dose coverage to the affected vocal cord and the dose delivered to the organs at risk using conventional, intensity-modulated radiotherapy (IMRT) coplanar, and IMRT non-coplanar techniques. Methods and Materials: For 10 patients, conventional treatment plans using two laterally opposed wedged 6-MV photon beams were calculated in XiO (Elekta-CMS treatment planning system). An in-house IMRT/beam angle optimization algorithm was used to obtain the coplanar and non-coplanar optimized beam angles. Using these angles, the IMRT plans were generated in Monaco (IMRT treatment planning system, Elekta-CMS) with the implemented Monte Carlo dose calculation algorithm. The organs at risk included the contralateral vocal cord, arytenoids, swallowing muscles, carotid arteries, and spinal cord. The prescription dose was 66 Gy in 33 fractions. Results: For the conventional plans and coplanar and non-coplanar IMRT plans, the population-averaged mean dose ± standard deviation to the planning target volume was 67 ± 1 Gy. The contralateral vocal cord dose was reduced from 66 ± 1 Gy in the conventional plans to 39 ± 8 Gy and 36 ± 6 Gy in the coplanar and non-coplanar IMRT plans, respectively. IMRT consistently reduced the doses to the other organs at risk. Conclusions: Single vocal cord irradiation with IMRT resulted in good target coverage and provided significant sparing of the critical structures. This has the potential to improve the quality-of-life outcomes after RT and maintain the same local control rates. 2012 Elsevier Inc. Image-guided radiotherapy, Intensity-modulated radiotherapy, Early glottic carcinoma, Normal tissue sparing, Quality of life.

Inhibition of ataxia telangiectasia related-3 (ATR) improves therapeutic index in preclinical models of non-small cell lung cancer (NSCLC) radiotherapy

BACKGROUND AND PURPOSE To evaluate the impact of ATR inhibition using AZD6738 in combination with radiotherapy on the response of non-small cell lung cancer (NSCLC) tumour models and a murine model of radiation induced fibrosis. MATERIALS AND METHODS AZD6738 was evaluated as a monotherapy and in combination with radiation in vitro and in vivo using A549 and H460 NSCLC models. Radiation induced pulmonary fibrosis was evaluated by cone beam computed tomography (CBCT) and histological staining. RESULTS AZD6738 specifically inhibits ATR kinase and enhanced radiobiological response in NSCLC models but not in human bronchial epithelial cells (HBECs) in vitro. Significant tumour growth delay was observed in cell line derived xenografts (CDXs) of H460 cells (p<0.05) which were less significant in A549 cells. Combination of AZD6738 with radiotherapy showed no significant change in lung tissue density by CBCT (p>0.5) and histological scoring of radiation induced fibrosis (p>0.5). CONCLUSION Inhibition of ATR with AZD6738 in combination with radiotherapy increases tumour growth delay without observable augmentation of late radiation induced toxicity further underpinning translation towards clinical evaluation in NSCLC.

EP-1699: 10MV un-flattened photon beams in prostate and pelvic node VMAT SABR; is the high energy necessary?

ESTRO 35 2016 _____________________________________________________________________________________________________ Conclusion: With this method calculations inaccuracies caused by the high density materials are avoided. We recommend the discussion of the use of the technique proposed with the physician for each treatment of head and neck patient with dental prostheses. The techniques in this study are being developed currently for VMAT technique.