Severe late toxicity after CCRT is common. Older age, advanced T-stage, and larynx/hypopharynx primary site were strong independent risk factors. Neck dissection after CCRT was associated with an increased risk of these complications.

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A B S T R A C T PurposeTo investigate the feasibility of intensity-modulated radiation therapy (IMRT) with or without chemotherapy, and to assess toxicities, failure patterns, and survivals in patients with nasopharyngeal carcinoma (NPC). Patients and MethodsRadiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any Nϩ disease and 59.4 Gy given to subclinical disease, delivered over 33 treatment days. Patients with stage T2b or greater or with Nϩ disease also received concurrent cisplatin (100 mg/m 2 ) on days 1, 22, and 43 followed by adjuvant cisplatin (80 mg/m 2 ) on day 1; fluorouracil (1,000 mg/m 2 /d) on days 1 through 4 administered every 4 weeks for three cycles. Tumor, clinical status, and acute/late toxicities were assessed. The primary objective was to test the transportability of IMRT to a multi-institutional setting. February 2003 and November 2005, 68 patients with stages I through IVB NPC (of which 93.8% were WHO types 2 and 3) were enrolled. Prescribed IMRT (target delineation) was given to 83.8%, whereas 64.9% received chemotherapy per protocol. The estimated 2-year local progression-free (PF), regional PF, locoregional PF, and distant metastasis-free rates were 92.6%, 90.8%, 89.3%, and 84.7%, respectively. The estimated 2-year PF and overall survivals were 72.7% and 80.2%, respectively. Acute grade 4 mucositis occurred in 4.4%, and the worst late grade 3 toxicities were as follows: esophagus, 4.7%; mucous membranes, 3.1%; and xerostomia, 3.1%. The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only two patients complained of grade 3 xerostomia, and none had grade 4 xerostomia. Results Between ConclusionIt was feasible to transport IMRT with or without chemotherapy in the treatment of NPC to a multi-institutional setting with 90% LRPF rate reproducing excellent reports from single institutions. Minimal grade 3 and lack of grade 4 xerostomia were encouraging.

Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.

A greyscale-based fully automatic deformable image registration algorithm, originally known as the 'demons' algorithm, was implemented for CT image-guided radiotherapy. We accelerated the algorithm by introducing an 'active force' along with an adaptive force strength adjustment during the iterative process. These improvements led to a 40% speed improvement over the original algorithm and a high tolerance of large organ deformations. We used three methods to evaluate the accuracy of the algorithm. First, we created a set of mathematical transformations for a series of patient's CT images. This provides a 'ground truth' solution for quantitatively validating the deformable image registration algorithm. Second, we used a physically deformable pelvic phantom, which can measure deformed objects under different conditions. The results of these two tests allowed us to quantify the accuracy of the deformable registration. Validation results showed that more than 96% of the voxels were within 2 mm of their intended shifts for a prostate and a head-and-neck patient case. The mean errors and standard deviations were 0.5 mm+/-1.5 mm and 0.2 mm+/-0.6 mm, respectively. Using the deformable pelvis phantom, the result showed a tracking accuracy of better than 1.5 mm for 23 seeds implanted in a phantom prostate that was deformed by inflation of a rectal balloon. Third, physician-drawn contours outlining the tumour volumes and certain anatomical structures in the original CT images were deformed along with the CT images acquired during subsequent treatments or during a different respiratory phase for a lung cancer case. Visual inspection of the positions and shapes of these deformed contours agreed well with human judgment. Together, these results suggest that the accelerated demons algorithm has significant potential for delineating and tracking doses in targets and critical structures during CT-guided radiotherapy.

Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.