[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Combined PET/CT imaging has been proposed as an integral part of radiotherapy treatment planning (TP). Contrast-enhanced CT (ceCT) images are frequently acquired as part of the PET/CT examination to support target delineation. The aim of this dosimetric planning study was to investigate the error introduced by using a ceCT for intensity modulated radiotherapy (IMRT) TP with Monte Carlo dose calculation for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Nine patients with NSCLC prior to chemo-RT were included in this retrospective study. For each patient non-enhanced, low-dose CT (neCT), ceCT and [(18)F]-FDG-PET emission data were acquired within a single examination. Manual contouring and TP were performed on the ceCT. An additional set of independent target volumes was auto-segmented in PET images. Dose distributions were recalculated on the neCT. Differences in dosimetric parameters were evaluated. RESULTS: Dose differences in PTV and lungs were small for all patients. The maximum difference in all PTVs when using ceCT images for dose calculation was -2.1%, whereas the mean difference was less than -1.7%. Maximum differences in the lungs ranged from -1.8% to 2.1% (mean: -0.1%). In four patients an underestimation of the maximum spinal cord dose between 2% and 3.2% was observed, but treatment plans remained clinically acceptable. CONCLUSIONS: Monte Carlo based IMRT planning for NSCLC patients using ceCT allows for correct dose calculation. A direct comparison to neCT-based treatment plans revealed only small dose differences. Therefore, ceCT-based TP is clinically safe as long as the maximum acceptable dose to organs at risk is not approached.
[Show abstract][Hide abstract] ABSTRACT: The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy. However, a considerable number of patients are not eligible for standard lung surgery due to poor pulmonary function or comorbidities. We evaluated the efficacy and tolerability of intensity-modulated stereotactic radiotherapy (IMSRT) with moderate hypofractionation for these patients. Twelve patients were selected for IMSRT. 4D-CT planning was performed by gating CT-scanning positioning. The applied doses ranged between 10x4.5 Gy (80% ID) (N=1), 12x4.5 Gy (95% ID) (N=1) and 10x5.5 Gy (95% ID) (N=10). Long-term follow-up was performed including spirometry and CT for evaluation of local, locoregional and distant control. Even in patients with poor pulmonary function IMRST was safe and well tolerated. No severe acute adverse effects were observed. Estimated local control at 2 years was 90%. Moreover, IMSRT does not induce a significant deterioration of pulmonary function. IMRST is safe and feasible even for patients with very poor pulmonary function. The applied dose provides a high local control rate, although the biological equivalent dose (BED) is lower compared to the average of other SRT regimens. Therefore, IMRST may be an efficient alternative for all NSCLC stage I patients with contraindications to standard lobectomy especially in patients with small tumors in high-risk localisations.
[Show abstract][Hide abstract] ABSTRACT: Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine.
This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy, in patients aged 18 years or older with pathological stage II-III locally advanced rectal cancer from 35 German institutions. Patients in the capecitabine group were scheduled to receive two cycles of capecitabine (2500 mg/m(2) days 1-14, repeated day 22), followed by chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) days 1-38), then three cycles of capecitabine. Patients in the fluorouracil group received two cycles of bolus fluorouracil (500 mg/m(2) days 1-5, repeated day 29), followed by chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 mg/m(2) daily), then two cycles of bolus fluorouracil. The protocol was amended in March, 2005, to allow a neoadjuvant cohort in which patients in the capecitabine group received chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) daily) followed by radical surgery and five cycles of capecitabine (2500 mg/m(2) per day for 14 days) and patients in the fluorouracil group received chemoradiotherapy (50·4 Gy plus infusional fluorouracil 1000 mg/m(2) days 1-5 and 29-33) followed by radical surgery and four cycles of bolus fluorouracil (500 mg/m(2) for 5 days). Patients were randomly assigned to treatment group in a 1:1 ratio using permuted blocks, with stratification by centre and tumour stage. The primary endpoint was overall survival; analyses were done based on all patients with post-randomisation data. Non-inferiority of capecitabine in terms of 5-year overall survival was tested with a 12·5% margin. This trial is registered with ClinicalTrials.gov, number NCT01500993.
Between March, 2002, and December, 2007, 401 patients were randomly allocated; 392 patients were evaluable (197 in the capecitabine group, 195 in the fluorouracil group), with a median follow-up of 52 months (IQR 41-72). 5-year overall survival in the capecitabine group was non-inferior to that in the fluorouracil group (76% [95% CI 67-82] vs 67% [58-74]; p=0·0004; post-hoc test for superiority p=0·05). 3-year disease-free survival was 75% (95% CI 68-81) in the capecitabine group and 67% (59-73) in the fluorouracil group (p=0·07). Similar numbers of patients had local recurrences in each group (12 [6%] in the capecitabine group vs 14 [7%] in the fluorouracil group, p=0·67), but fewer patients developed distant metastases in the capecitabine group (37 [19%] vs 54 [28%]; p=0·04). Diarrhoea was the most common adverse event in both groups (any grade: 104 [53%] patients in the capecitabine group vs 85 [44%] in the fluorouracil group; grade 3-4: 17 [9%] vs four [2%]). Patients in the capecitabine group had more hand-foot skin reactions (62 [31%] any grade, four [2%] grade 3-4 vs three [2%] any grade, no grade 3-4), fatigue (55 [28%] any grade, no grade 3-4 vs 29 [15%], two [1%] grade 3-4), and proctitis (31 [16%] any grade, one [<1%] grade 3-4 vs ten [5%], one [<1%] grade 3-4) than did those in the fluorouracil group, whereas leucopenia was more frequent with fluorouracil than with capecitabine (68 [35%] any grade, 16 [8%] grade 3-4 vs 50 [25%] any grade, three [2%] grade 3-4).
Capecitabine could replace fluorouracil in adjuvant or neoadjuvant chemoradiotherapy regimens for patients with locally advanced rectal cancer.
Roche Pharma AG (Grenzach-Wyhlen, Germany).
The Lancet Oncology 04/2012; 13(6):579-88. DOI:10.1016/S1470-2045(12)70116-X · 24.73 Impact Factor