Adaptive radiotherapy for locally advanced non-small cell lung cancer, can we predict when and for whom?

BACKGROUND: Adaptive radiotherapy (ART) could be a tool to reduce toxicity and to facilitate dose escalation in stage III NSCLC. Our aim was to identify the most appropriate time and potential benefit of ART. MATERIAL AND METHODS: We analyzed volume reduction and dosimetric consequences of 41 patients who were treated with concurrent (cCRT) (n = 21) or sequential (sCRT) chemoradiotherapy to a median dose of 70 Gy, 2 Gy/F. At every treatment fraction a cone-beam CT (CBCT) was performed. The gross tumor volume (GTV-T) was adapted (exclusion of lymph nodes) to create the GTV-T-F1. Every fifth fraction (F5-F30), the GTV-T-F1 was adapted on the CBCT to create a GTV-T-Fx. Dose volume histograms were recalculated for every GTV-T-Fx, enabling to create lookup tables to predict the theoretical dosimetric advantage on common lung dose constraints. RESULTS: The average GTV reduction was 42.1% (range 4.0-69.3%); 50.1% and 33.7% for the cCRT and sCRT patients, respectively. A linear relationship between GTV-T-F1 volume and absolute volume decrease was found for both groups. The mean V5, V20, V30 and mean lung dose increased by 0.8, 3.1, 5.2 and 3.4%, respectively. A larger increase (p < 0.05) was observed for peripheral tumors and cCRT. Lookup tables were generated. CONCLUSION: ART offers the most beneficial dosimetric effects when performed around fraction 15, especially for patients with a large initial GTV-T treated by cCRT.

Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

Evaluation of the Sinmed Mastercouch as replacement for a standard couch.

BACKGROUND AND PURPOSE: Introducing into practice a new carbon-fibre couch necessitates its evaluation with regard to the present clinical situation. MATERIALS AND METHODS: In this study, a geometric and dosimetric evaluation has been made for the Sinmed Mastercouch as a replacement for the Elekta C-arm couch with Mylar-tennis racket combination. Geometrically, feasible gantry angles with regard to collision and beam intersection were discriminated as function of isocentric table rotation for 10 treatment isocentres. Dosimetrically, the build-up distortion and attenuation by the aforementioned tabletops and a carbon-fibre tabletop of an Elekta Precise simulator was measured. Finally, the clinical implications of these influences were assessed for a 3-field prostate treatment in three configurations: Mastercouch, C-arm couch and no-intersection situation. RESULTS: With regard to collision, the largest advantages are observed for the Mastercouch with the Omega-shaped treatment module compared to the C-arm couch for isocentres located in the upper part of the body, thanks to its shape and the absence of any metal. Dosimetrically, one has to take into account the build-up loss and attenuation by beam intersection with Mastercouch and the carbon-fibre edges of the tennis racket (C-arm couch). The clinical relevance of these dosimetric aspects depends on the dose delivered by the compromised beams.

Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal cancer.

PURPOSE: In rectal cancer, combined radiotherapy and chemotherapy, either pre- or postoperatively, is an accepted treatment. Late small bowel (SB) toxicity is a feared side effect and limits radiation-dose escalation in a volume-dependent way. A planning strategy for intensity- modulated arc therapy (IMAT) was developed, and IMAT was clinically implemented with the aim to reduce the volume of SB irradiated at high doses and thus reduce SB toxicity. We report on the treatment plans of the first 7 patients, on the comparison of IMAT with conventional 3D planning (3D), and on the feasibility of IMAT delivery. METHODS AND MATERIALS: Seven patients, who were referred to our department for preoperative (n = 4) or postoperative (n = 3) radiotherapy for rectal cancer, gave written consent for IMAT treatment. All patients had a planning CT in prone position. The delineation of the clinical target volume was done after fusion of CT and MRI, with the help of a radiologist. For the IMAT plan, arcs were generated using an anatomy-based segmentation tool. The optimization of the arcs was done by weight optimization (WO) and leaf position optimization (LPO), both of which were adapted for IMAT purposes. The 3D plans used one posterior and two lateral wedged beams, of which the outlines were shaped to the beam's-eye view projection of the planning target volume (PTV). Beam WO was done by constrained matrix inversion. For dose-volume histogram analysis, all plans were normalized to 45 Gy as median PTV dose. Polymer gel dosimetry (PGD) on a humanoid phantom was used for the validation of the total chain (planning to delivery). IMAT treatments were delivered by an Elekta SliPlus linear accelerator using prototype software with the same interlock class as in clinical mode. RESULTS: The IMAT plan resulted in 3 to 6 arcs, with a mean delivery time of 6.3 min and a mean of 456 monitor units (MU) for a 180 cGy fraction. The minimal dose in the PTV was not significantly different between 3D and IMAT plans. Inhomogeneity was highest for the IMAT plans (14.1%) and lowest for the 3D plans (9.9%). Mean dose to the SB was significantly lower for the IMAT plans (12.4 Gy) than for the 3D plans (17.0 Gy). The volume of SB receiving less than any dose level was lower for the IMAT plans than for 3D plans. Integral dose was lower in the IMAT plans than for the 3D plans (respectively 244 J and 262 J to deliver 45 Gy). Differences between the PGD measured dose and the calculated dose were as small for IMAT as for 3D treatments. CONCLUSION: IMAT plans are deliverable within a 5-10-minute time slot, and result in a lower dose to the SB than 3D plans, without creating significant underdosages in the PTV. PGD showed that IMAT delivery is as accurate as 3D delivery.

Intensity-modulated radiotherapy for recurrent and second primary head and neck cancer in previously irradiated territory.

PURPOSE: To evaluate re-irradiation using IMRT for recurrent and second primary head and neck cancer in previously irradiated territory. MATERIALS AND METHODS: Between 1997 and 2008, 84 patients with recurrent and second primary head and neck cancer were treated with IMRT to a median dose of 69 Gy. Median time interval between initial radiotherapy and re-irradiation was 49.5 (5.2-298.3) months. Salvage surgery preceded re-irradiation in 19 patients; 17 patients received concurrent chemotherapy. RESULTS: Median follow-up of living patients was 19.8 (1.9-76.1) months. Five-year locoregional control and overall survival were 40% and 20%, respectively. Five-year disease-specific survival and disease-free survival were 29% and 15%, respectively. Stage T4 (p=0.015), time interval between initial treatment and re-irradiation (p=0.011) and hypopharyngeal cancer (p=0.013) were independent prognostic factors for worse overall survival in multivariate analysis. Twenty-six and 11 patients developed Grade 3 acute and late toxicity, respectively. No Grade 5 acute toxicity was encountered. There were 2 fatal vascular ruptures during follow-up. CONCLUSIONS: High-dose IMRT for recurrent and second primary head and neck cancer in previously irradiated territory leads to approximately 20% long-term survival in a non-selected patient population. Identification of patients who would benefit most of curative IMRT is warranted.