P. Graff

Intensity-modulated radiotherapy in head and neck cancer: Results of the prospective study GORTEC 2004–03

BACKGROUND AND PURPOSE In 2003, the French Authority for Health (HAS) recommended the use of intensity modulated radiotherapy (IMRT) in prospective trial before its routine use. The Oncology and Radiotherapy Group for Head and Neck Cancer (GORTEC) proposed to evaluate prospectively acute and late toxicities, locoregional control and overall survival for patients treated for head and neck cancer (HNC) with IMRT and bilateral neck irradiation. MATERIALS AND METHODS Between 2002 and 2008, 208 patients with HNC were treated with IMRT in 8 centres. There were 38 nasopharynx, 117 oropharynx, 25 pharyngo-larynx, 24 oral cavity and 4 unknown primary (28.5% stage I-II and 71% Stage III-IV). Ninety-three patients (46%) had postoperative IMRT and 78 patients (37.5%) received concurrent chemotherapy. The doses were 70 Gy to the gross tumour, 66 Gy to the high-risk postoperative sites and 50 Gy to the subclinical disease. Toxicities were graded according to the RTOG-EORTC scales. RESULTS The median follow-up was 25.3 months (range: 0.4-72 months). There were 29 local-regional failures: 24 were in-field, three were marginal and one was out-field. The two-year loco-regional control and overall survival were 86% and 86.7%, respectively. At 18 months, grade ≥ 2 xerostomia was 16.1%. A mean dose to the spared parotid below 28 Gy led to significantly less grade ≥ 2 xerostomia (8.5% vs 24%) with a relative risk of 1.2 [95% CI: 1.02-1.41, p = 0.03]. Grade ≥ 2 xerostomia increased by approximately 3% per Gy of mean parotid dose up to 28, Gy then 7% per Gy above 33 Gy. CONCLUSIONS IMRT for HN cancer seems to reduce late toxicities without jeopardising local control and overall survival.

Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer.

PURPOSE Recurrent head and neck cancer is associated to a poor survival prognosis. A high toxicity rate is demonstrated when surgery and/or radiotherapy and/or chemotherapy are combined. Furthermore, the duration of treatment is often not ethically compatible with the expected survival (median survival<1year). Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. After completion of a feasibility study, results of a multicentric study (Lille, Nancy & Nice) using SBRT with cetuximab are reported. The aim of the study was to deliver non toxic short course SBRT (2weeks) in order to get the same local control as the one demonstrated with longer protocols. METHODS AND MATERIALS Patients with inoperable recurrent, or new primary tumor in a previously irradiated area, were included (WHO<3). Reirradiation (RT) dose was 36Gy in six fractions of 6Gy to the 85% isodose line covering 95% of the PTV with 5 injections of concomitant cetuximab (CT). All patients had previous radiotherapy, 85% had previous surgery and 48% previous chemotherapy. RESULTS Between 11/2007 and 08/2010, 60 were included (46 men and 14 women), 56 received CT+RT, 3 were not treated and 1 received only CT. Median age was 60 (42-87)) and all 56 patients had squamous carcinoma and received concomitant cetuximab. Mean time between previous radiotherapy and the start of SBRT was 38months. Cutaneous toxicity was observed for 41 patients. There was one toxic death from hemorrhage and denutrition. Median follow-up was 11.4months. At 3months, response rate was 58.4% (95% CI: 43.2-72.4%) and disease control rate was 91.7% (95% CI: 80.0-97.7%). The one-year OS rate was 47.5% (95% CI: 30.8-62.4). CONCLUSION These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. This combination may be the reference treatment is this population.

The Residual Setup Errors of Different IGRT Alignment Procedures for Head and Neck IMRT and the Resulting Dosimetric Impact

PURPOSE To assess residual setup errors during head and neck radiation therapy and the resulting consequences for the delivered dose for various patient alignment procedures. METHODS AND MATERIALS Megavoltage cone beam computed tomography (MVCBCT) scans from 11 head and neck patients who underwent intensity modulated radiation therapy were used to assess setup errors. Each MVCBCT scan was registered to its reference planning kVCT, with seven different alignment procedures: automatic alignment and manual registration to 6 separate bony landmarks (sphenoid, left/right maxillary sinuses, mandible, cervical 1 [C1]-C2, and C7-thoracic 1 [T1] vertebrae). Shifts in the different alignments were compared with each other to determine whether there were any statistically significant differences. Then, the dose distribution was recalculated on 3 MVCBCT images per patient for every alignment procedure. The resulting dose-volume histograms for targets and organs at risk (OARs) were compared to those from the planning kVCTs. RESULTS The registration procedures produced statistically significant global differences in patient alignment and actual dose distribution, calling for a need for standardization of patient positioning. Vertically, the automatic, sphenoid, and maxillary sinuses alignments mainly generated posterior shifts and resulted in mean increases in maximal dose to OARs of >3% of the planned dose. The suggested choice of C1-C2 as a reference landmark appears valid, combining both OAR sparing and target coverage. Assuming this choice, relevant margins to apply around volumes of interest at the time of planning to take into account for the relative mobility of other regions are discussed. CONCLUSIONS Use of different alignment procedures for treating head and neck patients produced variations in patient setup and dose distribution. With concern for standardizing practice, C1-C2 reference alignment with relevant margins around planning volumes seems to be a valid option.

Does IGRT ensure target dose coverage of head and neck IMRT patients

PURPOSE To determine if image-guided radiotherapy (IGRT) ensures dose coverage to the target, and to assess the dosimetric impact of anatomic changes using megavoltage cone-beam CT (MVCBCT) for patient positioning during head and neck IMRT. METHODS AND MATERIALS Forty-eight MVCBCT from 10 head and neck IMRT/IGRT patients were analyzed off-line. Target volumes and organs at risk (OARs) contours delineated on CT were transferred and adjusted on MVCBCT images. Each MVCBCT was processed to allow dose recalculation, resulting in 469 dose-volume histograms (DVHs). The concept of dosimetric latitude was introduced to provide a clinical perspective. RESULTS MVCBCT target DVHs showed a moderate level of difference in D95 (dose to ≥95% of volume), generally less than a 5% difference from the planned dose. Delivered-dose increases to the spinal cord and brainstem showed no apparent time trend. The 4mm margin around OARs was a useful precaution to prevent exceeding critical dose thresholds. The parotid glands showed progressive increases in mean dose related to shrinkage of the external contours. CONCLUSION IGRT repositioning ensured target volume coverage, but significant dose variations were observed for OARs. The dosimetric impact of anatomic changes during radiotherapy was of lesser importance than the effects of IGRT repositioning.

Evaluation of the Block Matching deformable registration algorithm in the field of head-and-neck adaptive radiotherapy

BACKGROUND AND PURPOSE To compare the accuracy of the Block Matching deformable registration (DIR) against rigid image registration (RIR) for head-and-neck multi-modal images CT to cone-beam CT (CBCT) registration. MATERIAL AND METHODS Planning-CT and weekly CBCT of 10 patients were used for this study. Several volumes, including medullary canal (MC), thyroid cartilage (TC), hyoid bone (HB) and submandibular gland (SMG) were transposed from CT to CBCT images using either DIR or RIR. Transposed volumes were compared with the manual delineation of these volumes on every CBCT. The parameters of similarity used for analysis were: Dice Similarity Index (DSI), 95%-Hausdorff Distance (95%-HD) and difference of volumes (cc). RESULTS With DIR, the major mean difference of volumes was -1.4 cc for MC, revealing limited under-segmentation. DIR limited variability of DSI and 95%-HD. It significantly improved DSI for TC and HB and 95%-HD for all structures but SMG. With DIR, mean 95%-HD (mm) was 3.01 ± 0.80, 5.33 ± 2.51, 4.99 ± 1.69, 3.07 ± 1.31 for MC, TC, HB and SMG, respectively. With RIR, it was 3.92 ± 1.86, 6.94 ± 3.98, 6.44 ± 3.37 and 3.41 ± 2.25, respectively. CONCLUSION Block Matching is a valid algorithm for deformable multi-modal CT to CBCT registration. Values of 95%-HD are useful for ongoing development of its application to the cumulative dose calculation.

Management of Patients with Head and Neck Tumours Presenting at Diagnosis with a Synchronous Second Cancer at Another Anatomic Site

AIMS To understand management strategies and outcomes of patients diagnosed with a head and neck tumour and a synchronous second cancer developed at another anatomic site. MATERIALS AND METHODS Retrospective analysis of all patients diagnosed with a head and neck carcinoma and a synchronous cancer and engaged in curative-intent treatments. To evaluate therapeutic strategies, each patients treatment process was divided into sequential therapeutic modalities and corresponding targets (head and neck and/or synchronous tumour) were identified. Patient outcome was analysed with an intent-to-treat approach. RESULTS Forty-three patients were entered into the study (mean age=57.4 years). Synchronous tumours concerned the lung (57.8%), oesophagus (31.1%) or other sites (11.1%). Treatments were complex, including one to four consecutive modalities, with a mean duration of 4.6 months. When both tumours were advanced, treatments were frequently initiated with dual-spectrum chemotherapy (66.7%). In other situations, a locoregional treatment was often (81.1%) proposed immediately. When both tumours were in early stages, this initial locoregional treatment could be extended to target both tumours together (30.0%). For patients whose tumours differed in severity, this locoregional treatment targeted only one tumour (85%); priority was given to the most advanced one (76.5%). Nine patients had definitive treatment interruption. Associated risk factors were a low body mass index (P=0.03) and advanced-stage tumours (P=0.01). Thirty-one patients died (72.1%) with a median time to death of 7.7 months. The median follow-up for survivors was 46.2 months. Three-year overall survival was 33.9%. Low body mass index (P=0.001), advanced-stage synchronous tumours (P=0.03) and oesophageal primaries (P=0.03) altered the overall survival. Three-year locoregional and metastatic progression-free survival was 40.8 and 62.5%, respectively. Low body mass index (P=0.01) and advanced-stage synchronous tumours (P=0.01) increased the risk of disease failure. CONCLUSIONS Head and neck tumours diagnosed with a synchronous cancer are a complex challenge. Despite a severe prognosis, patients who are not underweight, presenting with lower-stage tumours (especially the synchronous tumour) and without oesophageal involvement could most benefit from aggressive treatments.

Conventional Versus Automated Implantation of Loose Seeds in Prostate Brachytherapy: Analysis of Dosimetric and Clinical Results

PURPOSE To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation. METHODS AND MATERIALS 574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival. RESULTS 419 (73%) and 155 (27%) patients with low-risk and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P<.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed. CONCLUSION Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis<3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.

Radiothérapie adaptative des cancers ORL : un outil permettant d’identifier les patients nécessitant une adaptation de leur traitement

PURPOSE The purpose of this work was to implement a simple dosimetric alert tool in a retrospective study for six patients suffering from head and neck cancer to detect when a patient might require an adaptive radiotherapy. MATERIALS AND METHODS The dosimetric tool generates a 3D cartography of two dosimetric complementary information: a dose variation tolerance map and a dose differential map. The tolerance map is calculated on the initial scanner (CTinit) using the planned dose distribution. It shows for each voxel of each delineated volume the availability for local dose variations during the course of radiotherapy without exceeding the dose threshold. The differential dose map is generated on the tomographic image CBCT (CBCTtreatment). It shows dose variations between the planned and the actual delivered dose distribution for each voxel. By comparing both maps, when a voxel presents a value superior to the corresponding dose variation tolerance, an alert is generated and the anatomical areas concerned are visually indicated to the physician. RESULTS The application of the dosimetric tool on six patients with head and neck cancers reveals the ability of the tool to detect cases requiring a new treatment plan. Two patients whose the tumour shrinkage produced an increase of the delivered dose to the spinal cord beyond 45 Gy have been detected. CONCLUSION The development of the dosimetric tool allows the automatic detection, with no delineation needs, of patients suffering from head and neck cancers requiring an adaptive strategy.

A spatially encoded dose difference maximal intensity projection map for patient dose evaluation: A new first line patient quality assurance tool

PURPOSE To develop a spatially encoded dose difference maximal intensity projection (DD-MIP) as an online patient dose evaluation tool for visualizing the dose differences between the planning dose and dose on the treatment day. METHODS Megavoltage cone-beam CT (MVCBCT) images acquired on the treatment day are used for generating the dose difference index. Each index is represented by different colors for underdose, acceptable, and overdose regions. A maximal intensity projection (MIP) algorithm is developed to compress all the information of an arbitrary 3D dose difference index into a 2D DD-MIP image. In such an algorithm, a distance transformation is generated based on the planning CT. Then, two new volumes representing the overdose and underdose regions of the dose difference index are encoded with the distance transformation map. The distance-encoded indices of each volume are normalized using the skin distance obtained on the planning CT. After that, two MIPs are generated based on the underdose and overdose volumes with green-to-blue and green-to-red lookup tables, respectively. Finally, the two MIPs are merged with an appropriate transparency level and rendered in planning CT images. RESULTS The spatially encoded DD-MIP was implemented in a dose-guided radiotherapy prototype and tested on 33 MVCBCT images from six patients. The user can easily establish the threshold for the overdose and underdose. A 3% difference between the treatment and planning dose was used as the threshold in the study; hence, the DD-MIP shows red or blue color for the dose difference > 3% or < or = 3%, respectively. With such a method, the overdose and underdose regions can be visualized and distinguished without being overshadowed by superficial dose differences. CONCLUSIONS A DD-MIP algorithm was developed that compresses information from 3D into a single or two orthogonal projections while hinting the user whether the dose difference is on the skin surface or deeper.

Radiothérapie conformationnelle avec modulation d’intensité des cancers des voies aérodigestives supérieures : dose de tolérance de l’œil et des voies optiques

Radiation-induced damage of ocular, orbital and eyelid structures are mainly reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume relationships are, however, inaccurate due to the small volume of most of the organs at risk involved and limited ability of irradiation techniques to spare these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The ability of newest radiation techniques including IMRT and proton therapy to generate steep dose gradients may yield more accurate models in the future. Some toxicities are severe and irreversible, leading to vision loss, as in the case of radiation-induced optic neuropathy for which curative treatments are suboptimal. Other toxicities can lead to reversible vision loss but can be surgically corrected, as is the case for radiation-induced cataract. In this paper, we will review the dose effects for the ocular; orbital and eyelid structures.