Toward magnetic resonance-only simulation: segmentation of bone in MR for radiation therapy verification of the head.

PURPOSE: To develop a practical method to localize bones in magnetic resonance (MR) images, to create "computed tomography-like" MR images (ctMRI) that could be used for radiation therapy verification, and to generate MR-based digitally reconstructed radiographs (DRR). METHODS AND MATERIALS: Using T1-weighted MR images, an air mask was derived from the manual contouring of all airways within the head and neck region using axial images at 6 anatomic levels. Compact bone, spongy bone, and soft tissue masks were then automatically generated using the statistical data derived from MR intensities and the air mask. ctMRI were then generated by mapping the MR intensities of the voxels within these masks into the CT number ranges of corresponding tissues. MR-based DRRs created from ctMRI were quantitatively evaluated using the co-registered MR and CT head images of 20 stereotactic radiosurgery patients. Ten anatomical points, positioned on the skull segmented using a threshold of 300 HU, in CT and ctMRI, were used to determine the differences in distance between MR-based DRRs and CT-based DRRs, and to evaluate the geometric accuracy of ctMRI and MR-based DRRs. RESULTS: The bony structures were identified on ctMRI and were visible in the MR-based DRRs. From the 20 patient cases, the mean geometric difference and standard deviation between the 10 anatomical points on MR-based and CT-based DRRs was -0.05 ± 0.85 mm, respectively. This included uncertainty in image fusion. The maximum distance difference was 1.88 mm. CONCLUSIONS: A practical method was developed to segment bone from MR images. The ctMRI created can be used for radiation treatment verification when MR-only simulation is performed. MR-based DRRs can be used in place of CT-based DRRs.

Patient preferences for oropharyngeal cancer treatment de-escalation.

BACKGROUND: The excellent prognosis of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (SCCs) against severe chemoradiotherapy (CRT) toxicities has opened discussion of deintensification trials. The purpose of this study was to describe the perspective of patients with HPV-positive and HPV-negative disease toward such studies. METHODS: Fifty-one patients with oropharyngeal SCC (post-CRT) underwent semistructured interviews contrasting toxicities of radiotherapy (RT) alone and CRT. Patients were asked what potential difference in cancer survival was acceptable to prefer RT over CRT. Initially, survival rate was the same for both treatments, then the RT rate was reduced until the preference switched. Treatment experience and preference for deintensified CRT were collected. RESULTS: Ninety-percent of patients initially selected RT, but 69% switched to CRT after 0% to 5% reduction in survival. Patients that rated their treatment experience as mild would accept lower survival versus severe treatment (p = .02). Eighty-one percent of patients (33 of 40) indicated they preferred reduced chemotherapy in CRT. CONCLUSION: Patients accept little difference in survival between treatments to avoid toxicity.

A review of radiotherapy for merkel cell carcinoma of the head and neck.

Merkel cell carcinoma of the head and neck (MCCHN) presents a clinical challenge due to its aggressive natural history, unpredictable lymphatic drainage, and high degree of treatment related morbidity. Histological examination of the regional lymph nodes is very important in determining the optimal treatment and is usually achieved by sentinel lymph node biopsy. Radiotherapy plays a critical role in the treatment of most patients with MCCHN. Surgery with adjuvant radiotherapy to the primary tumour site is associated with high local control rates. If lymph nodes are clinically or microscopically positive, adjuvant radiotherapy is indicated to decrease the risk of regional recurrence. The majority of locoregional recurrences occur at the edge or just outside of the radiation field, reflecting both the inherent radiosensitivity of MCC and the importance of relatively large volumes to include "in-transit" dermal lymphatic pathways. When surgical excision of the primary or nodal disease is not feasible, primary radiotherapy alone should be considered as a potentially curative modality and confers good loco-regional control. Concurrent chemoradiotherapy is well tolerated and may further improve outcomes.

Kinetic stability of all-in-one parenteral nutrition admixtures in the presence of high dose Ca2+ additive under clinical application circumstances.

BACKGROUND: TPN infusions are usually administered during a treatment period of 10-24 hours per day due to the metabolic capacity of the liver. During this time interval physicochemically stable TPN solution (emulsion) is needed for the treatment. The purpose of the present study was to examine how the kinetic stability features of ready-made total parenteral nutrition admixtures containing olive oil and soybean oil will change under the usage-modeling 24-hour application with and without overdose Ca2+. METHODS: Particle size analysis and zeta potential measurements were carried out to evaluate the possible changes in the kinetic stability of the emulsions. RESULTS: Our results indicate that in two of the four mixtures bimodal droplet-size distribution figures were detected and appearance of fat particles over 5 µm can not be disclosed. The tendency for separation of large diameter droplets in the two types of oil-based emulsion systems was different. In case of soybean containing emulsion second peak of droplets appeared in the bottom of the container in contrast to the olive oil containing emulsions where the second peak appeared in the surface layer. Interestingly this phenomenon is independent of calcium-content. CONCLUSIONS: From therapeutic point the emulsions of the bigger droplets containing upper layer are safer because the potentially dangerous big droplets could remain in the infusion bag after the administration.

Evaluation of microscopic disease in oral tongue cancer using whole-mount histopathologic techniques: implications for the management of head-and-neck cancers.

PURPOSE: To map the distribution of microscopic disease (MD) in head-and-neck cancer by analyzing digital images of whole-mounted serial sections of tongue cancer specimens. METHODS AND MATERIALS: Ten T1-3 oral tongue cancer specimens were evaluated. The specimens were sliced into 3-mm blocks from which one or more 4-µm slides were taken and digitized to create whole-mounted serial sections. Gross tumor and microscopic disease were digitally contoured on each slide. Lines perpendicular to the gross tumor volume (GTV) edge were created at 0.05-mm intervals and the distance between GTV and MD measured. RESULTS: Of 88 slides assessed, 44 (50%) had evidence of MD. Of the 63,809 perpendicular lines drawn along the GTV edges, 2320 (3.6%) encountered microscopic disease along their path. The majority of MD abutted the GTV, and only 26.7% was noncontiguous with the GTV edge. The maximum distance from the border was 7.8 mm. Ninety-nine percent of all MD was within 4.75 mm and 95% was within 3.95 mm of the GTV. CONCLUSION: In this study we were able to assess the distribution of MD more accurately than has been possible with routine pathologic techniques. The results indicate that when the GTV is correctly identified, there is very little MD to be found outside this volume. This has implications for the volume of tissue resected at surgery and the volume included in the clinical target volume in conformal radiotherapy planning.

5-year review of a unique multidisciplinary nonmelanoma skin cancer clinic.

BACKGROUND: A multidisciplinary nonmelanoma skin cancer (NMSC) clinic is held weekly at our center, where all new patients are jointly assessed by dermatology/dermatopathology, radiation oncology, and plastic surgery. A new patient database was established in 2004. The purpose of this study was to provide a preliminary report on the patients seen in the NMSC clinic and the treatment recommendations rendered. METHODS: The new patient database was reviewed from January 2004 to December 2008, and patient demographics, tumor characteristics, and treatment recommendations were extracted. Cochran-Mantel-Harnszel (CMH) testing and chi-square analysis were used to detect any associations or relationships between variables within the database. A p value of less than .05 was considered significant. RESULTS: During the 5-year study period, 2,146 new patients were seen in the NMSC clinic. The majority of patients presented with basal cell carcinoma (64%) or squamous cell carcinoma (22%), with a median tumor size of 1 to 2 cm (range 0 to > 9 cm). Tumors were located in the head and neck region (80%), extremities (14%), and torso (6%). Previous treatment included biopsy only (62%), surgery (20%), electrodesiccation and curettage (11%), topical imiquimod (3%), and radiotherapy (1%). Treatment recommendations included surgery (55%) (with either simple excision [31%] or excision with margin control under frozen-section guidance [24%]), radiotherapy (19%), topical imiquimod (10%), observation (7%), and electrodesiccation and curettage (4%). CONCLUSIONS: The NMSC clinic at our center sees a high volume of patients who benefit from the multidisciplinary assessment provided. Treatment recommendations were based on patient and disease characteristics as well as patient preference.

On comparing the quality of head and neck IMRT plans delivered with two different linear accelerator manufacturers.

The purpose of this work was to determine whether 2 different types of linear accelerators manufacturers with similar MLC leaf widths deliver equivalent IMRT distributions for head and neck radiotherapy patients. In this study, plans delivered with Siemens linacs were re-optimized with an Elekta linac and vice versa. To test for significance, paired t-tests were computed to examine differences in target and normal tissue doses and monitor units. Dose distributions, dose-volume histograms, and dose to targets and normal tissues were found to be equivalent irrespective of the linac type. However, approximately 15% more monitor units were delivered when planned on the Elekta machine (p < 0.002). Both linear accelerators provide plans of comparable dosimetric quality; however, Elekta machines deliver slightly more monitor units than Siemens machines. This increase is likely due differences in geometric properties of the machine head designs, as modeled in the treatment planning system.

Accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer: long-term results.

PURPOSE: To retrospectively review the results of a single-institution series of accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer (NSCLC) in patients who are medically inoperable or who refuse surgery. METHODS AND MATERIALS: Peripherally located T1 to T3 N0 M0 tumors were treated with 48 to 60 Gy in 12 to 15 fractions between 1996 and 2007. No elective nodal irradiation was delivered. Patient, tumor, and treatment information was abstracted from the medical records. RESULTS: A total of 124 tumors were treated in 118 patients (56 male and 62 female). Median age at diagnosis was 76.3 years (range, 49-90 years). In all, 113 patients (95.8%) were not surgical candidates because of medical comorbidities. The 2- and 5-year overall survival (OS) rates were 51.0% and 23.3%, respectively, and the 2- and 5-year cause-specific survival (CSS) rates were 67.6% and 59.8%, respectively. The 2- and 5-year actuarial local control (LC) rates were 76.2% and 70.1%, respectively. Univariate analysis revealed that tumor size less than 3 cm compared with greater than 3 cm resulted in significantly improved OS (40.0% vs. 5.0% at 5 years; p = 0.0002), CSS (69.7% vs. 45.1% at 5 years; p = 0.0461), and a trend toward better LC (82.5% vs. 66.9% at 2 years, 76.6% vs. 60.8% at 5 years; p = 0.0685). Treatment was well tolerated and there were no treatment delays because of acute toxicity. CONCLUSIONS: Accelerated hypofractionated radiotherapy with 48 to 60 Gy using fractions of 4 Gy per day provides very good results for small tumors in medically inoperable patients with early-stage NSCLC.

Automated radiation targeting in head-and-neck cancer using region-based texture analysis of PET and CT images.

PURPOSE: A co-registered multimodality pattern analysis segmentation system (COMPASS) was developed to automatically delineate the radiation targets in head-and-neck cancer (HNC) using both (18)F-fluoro-deoxy glucose-positron emission tomography (PET) and computed tomography (CT) images. The performance of the COMPASS was compared with the results of existing threshold-based methods and radiation oncologist-drawn contours. METHODS AND MATERIALS: The COMPASS extracted texture features from corresponding PET and CT voxels. Using these texture features, a decision-tree-based K-nearest-neighbor classifier labeled each voxel as either "normal" or "abnormal." The COMPASS was applied to the PET/CT images of 10 HNC patients. Automated segmentation results were validated against the manual segmentations of three radiation oncologists using the volume, sensitivity, and specificity. The performance of the COMPASS was compared with three PET-based threshold methods: standard uptake value of 2.5, 50% maximal intensity, and signal/background ratio. RESULTS: The tumor delineations of the COMPASS were both quantitatively and qualitatively more similar to those of the radiation oncologists than the delineations from the other methods. The specificity was 95% +/- 2%, 84% +/- 9%, 98% +/- 3%, and 96% +/- 4%, and the sensitivity was 90% +/- 12%, 93% +/- 10%, 48% +/- 20%, and 68% +/- 25% for the COMPASS, for a standard uptake value of 2.5, 50% maximal intensity, and signal/background ratio, respectively. The COMPASS distinguished HNC from adjacent normal tissues with high physiologic uptake and consistently defined tumors with large variability in (18)F-fluoro-deoxy glucose uptake, which are often problematic with the threshold-based methods. CONCLUSION: Automated segmentation using texture analysis of PET/CT images has the potential to provide accurate delineation of HNC. This could lead to reduced interobserver variability, reduced uncertainty in target delineation, and improved treatment planning accuracy.

18F-fluorodeoxyglucose positron emission tomography-computed tomography for suspected recurrent papillary thyroid cancer: early experience at Sunnybrook Health Sciences Centre.

OBJECTIVES: To report the initial experience with combined 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) imaging for suspected recurrent papillary differentiated thyroid cancer (DTC) at Sunnybrook Health Sciences Centre (SHSC), Toronto. DESIGN: Single institution retrospective study. METHODS: Consecutive patients from SHSC who underwent FDG PET/CT imaging for suspected recurrent DTC over a period of 2.5 years were identified and their charts reviewed. MAIN OUTCOME MEASURE: Qualitative appraisal of FDG PET/CT imaging in suspected recurrent DTC. RESULTS: Sixteen patients (14F, 2M) were identified accounting for 17 FDG PET/CT scans. Three scans (18%) in 3 different patients were reported as suspicious for recurrent disease in the neck (1-3 lesions) and were considered "positive". All were subsequently confirmed pathologically (4-13 positive lymph nodes post operatively). Prior conventional imaging was abnormal in two patients. Two patients had an elevated non-stimulated thyroglobulin (TG) < 10 ng/mL (4.9 and 9.4). The remaining patient had a TG < 0.3 ng/mL but was anti-TG antibody positive (84 IUx10-3/L). With a median follow up of 15 months (range 7-36) there were no false positive or negative scans. Incidental pathology (breast cancer, large bowel polyps) was identified on a further 2/17 scans (12%). CONCLUSIONS: FDG PET/CT imaging is able to detect recurrent DTC in patients with low TG levels. It can complement conventional imaging findings and exclude distant FDG-avid metastases prior to surgery. It may underestimate the number of positive lymph nodes in the neck. Occult pathology may be identified with whole body FDG PET/CT.

Accelerated hypofractionation for early-stage non-small-cell lung cancer.

PURPOSE: To describe the outcome of treating early-stage non-small-cell lung cancer (NSCLC) with an accelerated hypofractionated course of radiotherapy. METHODS AND MATERIALS: A policy of treating early-stage NSCLC with a dose of 48 Gy in 12 once-daily fractions without elective irradiation of radiologically uninvolved regional nodes was adopted in 1996. We describe the outcome in 33 patients with NSCLC treated with this dose-fractionation schedule. RESULTS: The median patient age was 72.0 years. Most patients (75.8%) were not surgical candidates because of medical comorbidities or old age. For staging, 97.0% underwent CT of the thorax, and mediastinoscopy was performed in 6.1%. All patients had Stage T1-T2N0, except for 4 patients with positive nodes based on pathologically involved or clinically enlarged lymph nodes adjacent to the primary tumor. The overall survival rate was 80.1% at 1 year and 46.0% at 2 years. The median survival was 22.6 months. The cause-specific survival rate was 89.8% at 1 year and 54.1% at 2 years. The recurrence-free survival rate was 66.4% at 1 year and 40.0% at 2 years. Lateral radiotherapy field margins of <2 cm predicted for inferior overall survival, cause-specific survival, and recurrence-free survival on univariate and multivariate analyses (p <0.05). The most commonly reported toxicities were acute dermatitis (30.3%) and late cutaneous/subcutaneous fibrosis (24.2%). CONCLUSION: Accelerated hypofractionation for early-stage NSCLC appears to be safe and produces promising early results. Very small radiotherapy field margins may lead to an inferior outcome. Prospective studies are needed to determine the optimal dose-fractionation schedule.

The impact of (18)FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined non-small-cell lung carcinoma: a prospective study.

PURPOSE: To prospectively study the impact of coregistering (18)F-fluoro-deoxy-2-glucose hybrid positron emission tomographic (FDG-PET) images with CT images on the planning target volume (PTV), target coverage, and critical organ dose in radiation therapy planning of non-small-cell lung carcinoma. METHODS AND MATERIALS: Thirty patients with poorly defined tumors on CT, referred for radical radiation therapy, underwent both FDG-PET and CT simulation procedures on the same day, in radiation treatment position. Image sets were coregistered using external fiducial markers. Three radiation oncologists independently defined the gross tumor volumes, using first CT data alone and then coregistered CT and FDG-PET data. Standard margins were applied to each gross tumor volume to generate a PTV, and standardized treatment plans were designed and calculated for each PTV. Dose-volume histograms were used to evaluate the relative effect of FDG information on target coverage and on normal tissue dose. RESULTS: In 7 of 30 (23%) cases, FDG-PET information changed management strategy from radical to palliative. In 5 of the remaining 23 (22%) cases, new FDG-avid nodes were found within 5 cm of the primary tumor and were included in the PTV. The PTV defined using coregistered CT and FDG-PET would have been poorly covered by the CT-based treatment plan in 17--29% of cases, depending on the physician, implying a geographic miss had only CT information been available. The effect of FDG-PET on target definition varied with the physician, leading to a reduction in PTV in 24-70% of cases and an increase in 30-76% of cases. The relative change in PTV ranged from 0.40 to 1.86. On average, FDG-PET information led to a reduction in spinal cord dose but not in total lung dose, although large differences in dose to the lung were seen for a few individuals. CONCLUSION: The coregistration of planning CT and FDG-PET images made significant alterations to patient management and to the PTV. Ultimately, changes to the PTV resulted in changes to the radiation treatment plans for the majority of cases. Where possible, we would recommend that FDG-PET data be integrated into treatment planning of non-small-cell lung carcinoma, particularly for three-dimensional conformal techniques.