Pharyngeal Constrictor Dose-Volume Histogram Metrics and Patient-Reported Dysphagia in Head and Neck Radiotherapy.

AIMS: Head and neck radiotherapy long-term survival continues to improve and the management of long-term side-effects is moving to the forefront of patient care. Dysphagia is associated with dose to the pharyngeal constrictors and can be measured using patient-reported outcomes to evaluate its effect on quality of life. The aim of the present study was to relate pharyngeal constrictor dose-volume parameters with patient-reported outcomes to identify prognostic dose constraints. MATERIALS AND METHODS: A 64-patient training cohort and a 24-patient testing cohort of oropharynx and nasopharynx cancer patients treated with curative-intent chemoradiotherapy were retrospectively examined. These patients completed the MD Anderson Dysphagia Inventory outcome survey at 12 months post-radiotherapy to evaluate late dysphagia: a composite score lower than 60 indicated dysphagia. The pharyngeal constrictor muscles were subdivided into four substructures: superior, middle, inferior and cricopharyngeal. Dose-volume histogram (DVH) metrics for each of the structure combinations were extracted. A decision tree classifier was run for each DVH metric to identify dose constraints optimising the accuracy and sensitivity of the cohort. A 60% accuracy threshold and feature selection method were used to ensure statistically significant DVH metrics were identified. These dose constraints were then validated on the 24-patient testing cohort. RESULTS: Existing literature dose constraints only had two dose constraints performing above 60% accuracy and sensitivity when evaluated on our training cohort. We identified two well-performing dose constraints: the pharyngeal constrictor muscle D63% < 55 Gy and the superior-middle pharyngeal constrictor combination structure V31Gy < 100%. Both dose constraints resulted in ≥73% mean accuracy and ≥80% mean sensitivity on the training and testing patient cohorts. In addition, a pharyngeal constrictor muscle mean dose <57 Gy resulted in a mean accuracy ≥74% and mean sensitivity ≥60%. CONCLUSION: Mid-dose pharyngeal constrictor muscle and substructure combination dose constraints should be used in the treatment planning process to reduce late patient-reported dysphagia.

Absolute Percentage of Pattern 4 Disease as a Prognostic Measure for Intermediate-risk Prostate Cancer Treated with Stereotactic Body Radiotherapy.

AIMS: Intermediate-risk prostate cancer is heterogenous. The absolute percentage of biopsied tissue positive for Gleason pattern 4 disease (APP4) is a possible prognostic measure. Here we sought to determine the impact of APP4 in a prospective multi-institutional pooled analysis of men with intermediate-risk prostate cancer treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Patients with intermediate-risk prostate cancer treated with SBRT (40 Gy in five fractions or 26 Gy in two fractions) with or without androgen deprivation therapy treated on prospective clinical trials were included. Pathology reports were queried to obtain APP4, calculated as the percentage of Gleason pattern 4 disease within the tumour(s) multiplied by the percentage of total biopsied tissue positive for disease divided by 100. The optimal APP4 cut-off points for biochemical failure and distant metastasis were calculated and used as a stratification in the cumulative incidence of biochemical failure and distant metastasis. Multivariable competing risk models were developed. RESULTS: In tota, 227 patients were included. The median follow-up was 56.5 months. The optimal APP4 cut-off points were 5% for biochemical failure and 20% for distant metastasis. At 4 years, the cumulative incidence of biochemical failure was 23.6% and 2.3% for APP4 >5% and ≤ 5%, respectively (P < 0.0001). The cumulative incidence of distant metastasis was 12.5% for APP4 >20% and 1% for APP4 ≤ 20% (P = 0.02). APP4 sub-stratified favourable intermediate-risk prostate cancer and unfavourable intermediate-risk prostate cancer into groups at similarly low and similarly high risk of biochemical failure and distant metastasis. On multivariable competing risk analysis, APP4 >5% (P = 0.0004) was significantly associated with biochemical failure, but APP4 (log) was not for distant metastasis (P = 0.08). CONCLUSION: APP4 may be an easily accessible promising prognostic measure for patients with intermediate-risk prostate cancer treated with SBRT. Incorporation of APP4 into prospective trials will help to determine its value.

Active treatment in low-risk prostate cancer: a population-based study.

Background: Active surveillance instead of active treatment (at) is preferred for patients with low-risk prostate cancer (lr-pca), but practice varies widely. We conducted a population-based study to assess the proportion of patients who underwent at between January 2011 and December 2014, and to evaluate factors associated with at. Methods: The provincial cancer registry was linked to administrative health datasets to identify patients with lr-pca and to acquire demographic, tumour, and treatment data. The primary outcome was receipt of at during the first 12 months after diagnosis, defined as any receipt of external-beam radiotherapy, brachytherapy, radical prostatectomy, cryotherapy, or androgen deprivation. Univariate and multivariate logistic regression were used to analyze the correlation between patient and tumour factors and at. Results: Of 1565 patients with lr-pca, 554 (35.4%) underwent at within 12 months of diagnosis. Radical prostatectomy was the most common treatment (58%), followed by brachytherapy (29.6%). Younger age [odds ratio (or) 0.92; 95% confidence interval (ci): 0.91 to 0.94], lower score (≥3) on the Charlson comorbidity index (OR: 0.36; 95% ci: 0.19 to 0.68), T2 stage (or: 3.05; 95% ci: 2.03 to 4.58), higher prostate-specific antigen (psa) at diagnosis (or: 1.13; 95% ci: 1.06 to 1.21), radiation oncologist consultation (or: 3.35; 95% ci: 2.55 to 4.39), and earlier diagnosis year (2012 or: 0.46; 95% ci: 0.34 to 0.63; 2013 or: 0.45; 95% ci: 0.32 to 0.63; 2014 or: 0.33; 95% ci: 0.23 to 0.47) were associated with a higher probability of at. Conclusions: This contemporary population-based study demonstrates that approximately one third of patients with lr-pca undergo at. Patients of younger age, with less comorbidity, a higher tumour stage, higher psa, earlier year of diagnosis, and radiation oncologist consultation were more likely to undergo at. Further investigation is needed to identify strategies that could minimize overtreatment.

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials.

AIMS: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. MATERIALS AND METHODS: The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. RESULTS: In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS. CONCLUSION: The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

Endoscopic dilatation improves long-term dysphagia following head and neck cancer therapies: a randomized control trial.

Long-term pharyngeal dysphagia is a common complication following head and neck cancer (HNC) therapies. High-level evidence for pharyngoesophageal junction (POJ) dilatation as a treatment in this population is lacking. We aimed to evaluate the safety and efficacy of POJ dilatation in dysphagic HNC survivors. This single-center, single-blind, placebo-controlled trial (St George Hospital, Sydney, Australia) randomly assigned (1:1) HNC survivors with long-term dysphagia (≥12 months postcompleted HNC therapies) to receive either graded endoscopic dilatations or sham dilatation (placebo). Patients were blinded to intervention types. Two strata were used for permuted randomization: (1) HNC therapies (total laryngectomy vs. chemoradiation alone); (2) Prior POJ dilatation (nil vs. previous dilatation). The primary endpoint was a short-term clinical response in swallowing function (3 months), defined as (1) a decrease in Sydney Swallow Questionnaire score by ≥200 or a score ≤ ULN; and (2) satisfactory global clinical assessment. The secondary endpoints were dysphagia relapse and serious adverse events. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000707369). Between 13 January 2013 and 16 January 2017, 41 patients were randomly assigned to endoscopic dilatation (n = 21) or placebo (n = 20). The short-term response rate in the endoscopic dilatation group was 76% (n = 16), compared with 5% (n = 1) in the placebo group (P < 0.001). There were no serious adverse events. The finding of a mucosal tear postdilatation was associated strongly with clinical response (OR 13.4, 95% CI [2.4, 74.9], P = 0.003). Kaplan-Meier estimate of dysphagia relapse is 50% by 9.6 months (95% CI [6.0, 19.2]) from completion of dilatation. Endoscopic dilatation of the POJ is a safe and efficacious therapy for the treatment of long-term dysphagia in HNC survivors. Close follow-up and repeat dilatation are necessary given the high dysphagia relapse rate.

Dynamic Contrast-Enhanced MRI-Derived Intracellular Water Lifetime (τ i ): A Prognostic Marker for Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND AND PURPOSE: Shutter-speed model analysis of dynamic contrast-enhanced MR imaging allows estimation of mean intracellular water molecule lifetime (a measure of cellular energy metabolism) and volume transfer constant (a measure of hemodynamics). The purpose of this study was to investigate the prognostic utility of pretreatment mean intracellular water molecule lifetime and volume transfer constant in predicting overall survival in patients with squamous cell carcinomas of the head and neck and to stratify p16-positive patients based upon survival outcome. MATERIALS AND METHODS: A cohort of 60 patients underwent dynamic contrast-enhanced MR imaging before treatment. Median, mean intracellular water molecule lifetime and volume transfer constant values from metastatic nodes were computed from each patient. Kaplan-Meier analyses were performed to associate mean intracellular water molecule lifetime and volume transfer constant and their combination with overall survival for the first 2 years, 5 years, and beyond (median duration, >7 years). RESULTS: By the last date of observation, 18 patients had died, and median follow-up for surviving patients (n = 42) was 8.32 years. Patients with high mean intracellular water molecule lifetime (4 deaths) had significantly (P = .01) prolonged overall survival by 5 years compared with those with low mean intracellular water molecule lifetime (13 deaths). Similarly, patients with high mean intracellular water molecule lifetime (4 deaths) had significantly (P = .006) longer overall survival at long-term duration than those with low mean intracellular water molecule lifetime (14 deaths). However, volume transfer constant was a significant predictor for only the 5-year follow-up period. There was some evidence (P < .10) to suggest that mean intracellular water molecule lifetime and volume transfer constant were associated with overall survival for the first 2 years. Patients with high mean intracellular water molecule lifetime and high volume transfer constant were associated with significantly (P < .01) longer overall survival compared with other groups for all follow-up periods. In addition, p16-positive patients with high mean intracellular water molecule lifetime and high volume transfer constant demonstrated a trend toward the longest overall survival. CONCLUSIONS: A combined analysis of mean intracellular water molecule lifetime and volume transfer constant provided the best model to predict overall survival in patients with squamous cell carcinomas of the head and neck.

High-grade glioma management and response assessment-recent advances and current challenges.

The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques-including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging-can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology.

Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.

BACKGROUND: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. PATIENTS AND METHODS: DNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison. RESULTS: Among 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles. CONCLUSION: The genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.

Intra-fraction motion during extreme hypofractionated radiotherapy of the prostate using pre- and post-treatment imaging.

AIMS: To determine intra-fraction displacement of the prostate during extreme hypofractionated radiotherapy using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers. MATERIALS AND METHODS: In total, 265 image pairs were obtained from 53 patients who underwent extreme hypofractionated radiotherapy to a dose of 35 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal X-rays before and after treatment and were used to determine intra-fraction prostate displacement. RESULTS: The mean intra-fraction prostate displacements were -0.03 ± 0.61 mm (one standard deviation), 0.21 ± 1.50 mm and -0.86 ± 1.73 mm in the left-right, superior-inferior and anterior-posterior directions, respectively. The mean intra-fraction displacement during the first two fractions was moderately correlated with the displacement in the remaining three fractions, with correlation coefficients of 0.63 (95% confidence interval 0.43-0.77) and 0.47 (95% confidence interval 0.22-0.65) in the superior-inferior and anterior-posterior directions, respectively. There was no significant correlation in the left-right direction with a coefficient of -0.04 (95% confidence interval -0.31-0.23). CONCLUSIONS: The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5 mm warrants further validation.

Prediction of disease-free survival in patients with squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Patients with HNSCC have a poor prognosis and development of imaging biomarkers that predict long-term outcome might aid in planning optimal treatment strategies. Therefore, the purpose of the present study was to predict disease-free survival in patients with HNSCC by using pretreatment K(trans) measured from dynamic contrast-enhanced MR imaging. MATERIALS AND METHODS: Sixty-six patients with HNSCC were recruited from January 2005 to October 2008. Three patients were excluded because they underwent upfront neck dissection, and 6 patients were excluded due to suboptimal MR imaging data or being lost to follow-up. Disease-free survival was measured in the remaining 57 patients from the end date of chemoradiation therapy. In patients who died, the end point was the date of death, while in surviving patients the date of last clinical follow-up was used as the end point. Pretreatment K(trans) and nodal volume were computed from the largest metastatic node, and median pretreatment K(trans) and volume were used to divide patients into 2 groups (at or above the threshold value [group I] and below the threshold value [group II]. Disease-free survival was analyzed by the Kaplan-Meier method, and the results were compared by using a logrank test with K(trans) and nodal volume as predictors. A P value <.05 was considered significant. RESULTS: Thirteen of 57 patients had died of HNSCC by the last follow-up period (March 31, 2009). Patients with higher pretreatment K(trans) values had prolonged disease-free survival compared with patients with lower K(trans) values (P=.029). However, there was no significant difference in disease-free survival when nodal volume was used as a predictor (P=.599). CONCLUSIONS: Pretreatment K(trans) may be a useful prognostic marker in HNSCC.

Injection augmentation of arytenoids after partial laryngectomy: case series.

BACKGROUND: We undertook collagen injection laryngoplasty to achieve arytenoid augmentation in patients with dysphagia and persistent aspiration following partial laryngectomy, and we evaluated the efficacy of arytenoid augmentation in aiding neoglottic closure and ensuring airway safety. METHODS: Two patients with persistent swallowing impairment after partial laryngectomy were studied. Swallowing was evaluated using fibre-optic endoscopy, and modified barium swallow study. Collagen was then injected into the arytenoid mucosa to achieve neoglottic competence. RESULTS: The patients were followed up for up to two years. Both patients showed a marked improvement in neoglottic competence, as evaluated by fibre-optic and flexible endoscopy at three-month and one-year follow-up appointments. CONCLUSION: Arytenoid augmentation by injection laryngoplasty can be considered a safe and effective surgical tool for the treatment of dysphagia with persistent aspiration following partial laryngectomy.

Androgen deprivation therapy for prostate cancer-review of indications in 2010.

The discovery of androgen deprivation therapy (ADT) has been one of the most important advances in the treatment of prostate cancer. Here, the indications for the use of ADT are reviewed, together with the data supporting each indication. The settings for ADT use include cytoreduction; combined ADT and radiotherapy; pathologic node-positive disease; and recurrent, metastatic, or progressive prostate cancer.

Application of machine learning methodology for PET-based definition of lung cancer.

We applied a learning methodology framework to assist in the threshold-based segmentation of non-small-cell lung cancer (NSCLC) tumours in positron-emission tomography-computed tomography (PET-CT) imaging for use in radiotherapy planning. Gated and standard free-breathing studies of two patients were independently analysed (four studies in total). Each study had a pet-ct and a treatment-planning ct image. The reference gross tumour volume (GTV) was identified by two experienced radiation oncologists who also determined reference standardized uptake value (SUV) thresholds that most closely approximated the GTV contour on each slice. A set of uptake distribution-related attributes was calculated for each PET slice. A machine learning algorithm was trained on a subset of the PET slices to cope with slice-to-slice variation in the optimal suv threshold: that is, to predict the most appropriate suv threshold from the calculated attributes for each slice. The algorithm's performance was evaluated using the remainder of the pet slices. A high degree of geometric similarity was achieved between the areas outlined by the predicted and the reference SUV thresholds (Jaccard index exceeding 0.82). No significant difference was found between the gated and the free-breathing results in the same patient. In this preliminary work, we demonstrated the potential applicability of a machine learning methodology as an auxiliary tool for radiation treatment planning in NSCLC.

Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Tumor microenvironment, including blood flow and permeability, may provide crucial information regarding response to chemoradiation therapy. Thus, the objective of this study was to investigate the efficacy of pretreatment DCE-MR imaging for prediction of response to chemoradiation therapy in HNSCC. MATERIALS AND METHODS: DCE-MR imaging studies were performed on 33 patients with newly diagnosed HNSCC before neoadjuvant chemoradiation therapy by using a 1.5T (n = 24) or a 3T (n = 9) magnet. The data were analyzed by using SSM for estimation of K(trans), v(e), and tau(i). Response to treatment was determined on completion of chemoradiation as CR, with no evidence of disease (clinically or pathologically), or PR, with pathologically proved residual tumor. RESULTS: The average pretreatment K(trans) value of the CR group (0.64 +/- 0.11 minutes(-1), n = 24) was significantly higher (P = .001) than that of the PR (0.21 +/- 0.05 minutes(-1), n = 9) group. No significant difference was found in other pharmacokinetic model parameters: v(e) and tau(i), between the 2 groups. Although the PR group had larger metastatic nodal volume than the CR group, it was not significantly different (P = .276). CONCLUSIONS: These results indicate that pretreatment DCE-MR imaging can be potentially used for prediction of response to chemoradiation therapy of HNSCC.

Assessment of tumor angiogenesis as a prognostic factor of survival in patients with oligodendroglioma.

According to World Health Organization (WHO) and Daumas-Duport grading systems, progression of oligodendrogliomas (ODGs) to a higher grade (WHO grade III, grade B) is associated with increased angiogenesis. Based on multivariate assessment of molecular, pathological, and radiological parameters, we further assessed the influence of tumor angiogenesis on tumor progression and patient survival. Patients with a diagnosis of ODG, consecutively treated in a single institution, were reviewed and reclassified according to WHO and Daumas-Duport grading systems. MRI scans were reviewed to assess contrast enhancement and necrosis. Tissue sections were used for pathology review and to evaluate immunostaining of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGF-R), Ki-67, and CD34. Multivariate analysis was performed to assess the impact of tumor angiogenesis-related pathological and radiological factors on patient survival. One hundred thirty-four patients with pure ODG were included in this study. Multivariate analysis identified four independent poor prognostic factors: necrosis, absence of seizure, increased vascularization, and age >55 years. A subgroup of patients with tumor necrosis, increased vascularization, and absence of seizures had a significantly worse outcome than predicted, with a median overall survival of 14.2 months. VEGF expression was significantly higher in this subgroup and correlated with disease progression regardless of histologic grade. Based on the presence of radiological or pathological necrosis, contrast enhancement or endothelial hyperplasia, and absence of seizures, a high risk group of ODG can be identified with significantly worse overall survival. Also, VEGF over-expression in ODG constitutes an early marker for predicting tumor progression.

Adjuvant treatment of anaplastic oligodendrogliomas and oligoastrocytomas.

BACKGROUND: AO and AOA are known to be chemosensitive tumors. However, the impact of adding chemotherapy to surgery and radiotherapy has not been studied. Also, the value of chromosome 1p and 19q deletions as prognostic and predictive markers is only beginning to be defined. OBJECTIVES: After surgery, to compare radiotherapy (RT) plus chemotherapy versus RT alone (standard of care) in adults with newly diagnosed AO or mixed AOA. To investigate the prognostic and predictive value of loss of heterozygosity of chromosomes 1p and 19q. Outcomes analyzed include overall survival (OS), progression-free survival (PFS), and treatment toxicity greater than or equal to grade 3. SEARCH STRATEGY: Cochrane Central Register for Controlled Trials (CENTRAL, Issue 4,2006), MEDLINE (1966 to 2006) and EMBASE (1988 to 2006) were searched. Reference lists from relevant studies were scanned for any additional relevant articles. SELECTION CRITERIA: RCTs of adults with AO or mixed AOA comparing surgery plus RT versus surgery plus RT plus chemotherapy were included. No specific chemotherapy regimens were excluded. DATA COLLECTION AND ANALYSIS: Relevant studies were critically appraised and data was extracted. Based on the differences in patient selection with respect to the definition of AO (2 versus 3 high risk anaplastic features) and sequence of treatment (RT and chemotherapy), the results from the two RCTs were not able to be considered for meta-analysis. MAIN RESULTS: Two RCTs have tested surgery plus RT plus early procarbazine, lomustine, and vincristine (PCV) chemotherapy versus surgery plus RT alone. Neither study observed a survival benefit with the addition of early PCV chemotherapy. However, both studies found a statistically significant increase in PFS associated with the administration of PCV chemotherapy before surgery or after surgery and RT, with the benefit ranging from 10 to 11 months. Co-deletion of chromosomes 1p and 19q identifies a favorable subgroup of tumors with better overall survival outcomes. The predictive value of 1p and 19q co-deletions is less clear with one study observing a longer PFS with chemotherapy, while the other study did not. AUTHORS' CONCLUSIONS: Early PCV chemotherapy in addition to standard treatment of surgery and RT does not improve OS in patients with AO or AOA. However, it does improve PFS. It also is associated with significant toxicities. Tumors with 1p and 19q co-deletions are associated with better OS and may indicate a more chemo-responsive tumor.

Treatment planning dosimetric parameters for a (90)Y coil source used in intravascular brachytherapy.

BACKGROUND: (90)Y coil sources have been used in animal and clinical trials for treatment of restenosis in intravascular brachytherapy (IVBT). This study aims to determine the American Association of Physicists in Medicine (AAPM) Task Group-60 (TG-60) dosimetric quantities in regions surrounding the balloon wall for use in treatment planning computer systems. METHODS: The Monte Carlo method was used to determine the dose distribution, using MCNP4B2 code. The coil source was modeled by a hollow cylinder of 2.9 cm length centered in a balloon (2.5 mm diameter) filled with carbon dioxide (CO(2)) at 5 atm. Scoring voxels consisted of contiguous annular disk shells with 0.1 mm spacing in the radial direction and 0.2 mm spacing in the longitudinal direction. The scoring region ranges from the center of the source to 1.0 cm in the longitudinal direction, and from 0.13 to 1 cm in the radial direction. In the plane containing the source axis, the Monte Carlo-generated doses in rectilinear coordinates are converted to polar coordinates. RESULTS: The dose rate of the source is provided in both Cartesian and polar coordinates. The dose rate constant [D(r(0),theta(0))], anisotropy function [F(r,theta)], and radial dose function [g(r)] were generated from these values and listed in tabular format. At shallow angles and longer distances from the source center, large values of the anisotropy function resulted, deviating two orders of magnitude from unity. CONCLUSIONS The doses given to the intima, media, and adventitia are very crucial quantities in IVBT. The calculated TG-60 dosimetric quantities, used commonly in conventional brachytherapy applications, provide a means for the user to determine the three-dimensional dose surrounding the balloon catheter. These parameters can be used in future treatment planning system for IVBT. We also discuss the need to develop a new formalism specific to longer sources used in IVBT.

Potential molecular prognostic markers in head and neck squamous cell carcinomas.

BACKGROUND: Current management strategies for squamous cell carcinoma of the head and neck (HNSCC) rely on an understanding of the natural history of the disease, along with the use of prognostic factors to guide selection of appropriate treatment. However, it is recognized that tumor heterogeneity limits the reliable use of currently available prognostic markers. With the evolving understanding of the genetic and molecular basis of human malignancies, there has been much interest in determining whether specific molecular changes in HNSCC might guide treatment decisions. METHODS: A literature review of potential molecular markers relevant to HNSCC was undertaken and evaluated. It is evident that the published information is promising but, oftentimes, limited by a scarcity of large, uniformly staged and treated patients, from which the value of novel molecular markers can be assessed. RESULTS: On the basis of the review of more than 100 articles, some of the emerging molecular markers that might provide independent prognostic information include epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), cyclin D1, and p53. This review will discuss the current status of these molecular factors and consequent implications for novel therapeutic approaches for patients with HNSCC. CONCLUSION: With the evolving understanding that human malignancies have developed and progressed on the basis of accumulated molecular abnormalities, there is an existing body of work trying to determine whether such abnormalities can predict clinical behavior of HNSCC. Such studies have to be conducted rigorously to derive useful information. Nevertheless, the role of such molecular markers, and the possibility to exploit them for therapeutic gain, is already at the horizon.

Ytterbium-169: a promising new radionuclide for intravascular brachytherapy.

PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.02