Biomedical subjects

Roger Ove

Publications and source records attributed to Roger Ove.

7 recordsLinked to original sources

PubMed2006

Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.

BACKGROUND: We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS: Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS: The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P=0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P=0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P=0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS: Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Adult↗

PubMed2006

Intensity-modulated radiotherapy (IMRT) for carcinoma of the maxillary sinus: a comparison of IMRT planning systems.

The treatment of maxillary sinus carcinoma with forward planning can be technically difficult when the neck also requires radiotherapy. This difficulty arises because of the need to spare the contralateral face while treating the bilateral neck. There is considerable potential for error in clinical setup and treatment delivery. We evaluated intensity-modulated radiotherapy (IMRT) as an improvement on forward planning, and compared several inverse planning IMRT platforms. A composite dose-volume histogram (DVH) was generated from a complex forward planned case. We compared the results with those generated by sliding window fixed field dynamic multileaf collimator (MLC) IMRT, using sets of coplanar beams. All setups included an anterior posterior (AP) beam, and 3-, 5-, 7-, and 9-field configurations were evaluated. The dose prescription and objective function priorities were invariant. We also evaluated 2 commercial tomotherapy IMRT delivery platforms. DVH results from all of the IMRT approaches compared favorably with the forward plan. Results for the various inverse planning approaches varied considerably across platforms, despite an attempt to prescribe the therapy similarly. The improvement seen with the addition of beams in the fixed beam sliding window case was modest. IMRT is an effective means of delivering radiotherapy reliably in the complex setting of maxillary sinus carcinoma with neck irradiation. Differences in objective function definition and optimization algorithms can lead to unexpected differences in the final dose distribution, and our evaluation suggests that these factors are more significant than the beam arrangement or number of beams.

Female↗

PubMed2006

Doppler broadening effect on low-energy photon dose calculations using MCNP5 and PENELOPE.

Recent releases of the MCNP5 and PENELOPE Monte Carlo codes include the transport algorithm and momentum profiles that are necessary for accounting for Doppler broadening in Compton scattering processes. Such improvements might be particularly important in low-energy photon dose calculations. MCPLIB04 and PENDBASE (PENELOPE photon dataset) are based on the EPDL97 library with Compton momentum profiles, while MCPLIB03 and MCPLIB02 are based on the 1970's old library, with MCPLIB03 including the Compton momentum profiles. To isolate the dosimetric effects of Doppler broadening by the transport algorithm and Compton momentum profiles, we varied the choice of the above photon databases, in the same simulation geometry, using either version of MCNP5 or MCNP4 (no Doppler algorithm). We computed dose rate constants and dose distributions for r = 0.2-10 cm from a point source in a 50-cm-diameter sphere of water. Nine discrete energies for primary photon sources were chosen in the range of 10-150 keV. The results from both versions of MCNP with MCPLIB04 agreed with those of PENELOPE within statistical uncertainties (+/-1%) over the entire ranges of energies and radial distances investigated. MCNP5 with either MCPLIB03 or MCPLIB02 yielded almost identical data within statistical uncertainties (+/-1%) over the entire ranges of energies and radial distances investigated. This implies that in spite of the spectral broadening of scattered photons due to the orbital electron motion, the dosimetric effect of Doppler broadening for Compton interactions in water appears to be insignificant in the energy range investigated. The spectral dose analysis with and without the Doppler broadening supported this conclusion.

Algorithms↗

PubMed2004

Adenoviral vector-mediated augmentation of epidermal growth factor receptor (EGFr) enhances the radiosensitization properties of anti-EGFr treatment in prostate cancer cells.

PURPOSE: To determine whether an adenoviral vector approach to the augmentation of epidermal growth factor receptor (EGFr) expression results in increased antiproliferative and radiosensitization properties of anti-EGFr antibody therapy in prostate cancer cells. METHODS AND MATERIALS: DU145 and LNCaP human prostate cancer cells were used to test the above question in vitro. An adenoviral vector was utilized to transduce cells with an EGFr transgene (AdEGFr). Immunoblots were performed to measure EGFr expression and EGFr tyrosine phosphorylation. Radiolabeled ligand studies were employed to test binding of epidermal growth factor to EGFr. Scatchard analyses allowed for quantification of the number of EGFrs. Standard immunohistochemistry was performed to assess EGFr expression. Cellular proliferation was assessed after various combinations of treatment. RESULTS: Studies of prostate carcinoma cells infected with AdEGFr demonstrated an increase in EGFr expression. This increase in expression correlated with increased function of EGFr. Specifically, increased EGFr expression also resulted in increased ligand binding, ligand-induced internalization of EGFr, and ligand-induced EGFr tyrosine kinase activity that could be blocked with pre-exposure to IMC-C225 (an anti-EGFr monoclonal antibody). Transduction of the LNCaP cells with AdEGFr did not increase the antiproliferative effects of IMC-C225, but did significantly increase IMC-C225-induced radiosensitization as determined by cell proliferation. CONCLUSIONS: Augmentation of EGFr expression, through an adenoviral vector approach in prostate carcinoma cells, resulted in cells that demonstrated greater IMC-C225-induced radiosensitization compared to cells that were not treated with AdEGFr.

Adenoviridae↗

PubMed2003

Sequential annealing-gradient Gamma-Knife radiosurgery optimization.

Simulated annealing and gradient methods are commonly employed for inverse planning of radiotherapy delivery schemes. Annealing is effective in finding an approximation of the global solution, suffering from slow late convergence and in some cases poor dose homogeneity. Gradient methods converge well but not necessarily to the global minimum. We explored simulated annealing followed by gradient optimization to improve on either method alone, using radiosurgery as the model system. Simulated annealing and gradient inverse planning programs using the same objective function were adapted for radiosurgical optimization. The objective function chosen is a least-squares dose-matching function, with differential weighting of tissues. A simple test target allowing local minima in the objective function was evaluated. Two hundred trials using the gradient method were done. The gradient method approximated the global solution only 12% of the time, commonly finding a local minimum. The annealing-gradient technique converged to the global minimum in 78 out of 80 trials, more efficiently than annealing alone. Dose homogeneity was improved. In conclusion, sequential annealing-gradient optimization can improve on either method alone. The technique may be extensible to radiotherapy inverse planning in general, with benefit expected for problems characterized by slow gradient method convergence and local minima.

Algorithms↗

PubMed2003

Molecular targets as therapeutic strategies in the management of breast cancer.

Although the molecular and genetic determinants of most sporadic breast cancers remain unknown, increasing understanding of molecular and genetic events affecting breast carcinogenesis has provided information about the potential roles of specific biomarkers in tumour development and spread. It is now recognised that mutations of some tumour suppressor genes appear to play important early roles in the formation of some breast cancers. In addition, alterations in proto-oncogenes may contribute to the development of some breast cancers. The study of breast tumour biology at the molecular level has led to the development of targeted drug design, which provides a variety of agents targeted at specific molecules for the prevention, diagnosis and treatment of breast cancer. This review will describe the recognised molecular targets in breast cancer.

Angiogenesis Inhibitors↗

PubMed2002

Tumor control probability for selective boosting of hypoxic subvolumes, including the effect of reoxygenation.

PURPOSE: To study the effect on tumor control probability of selectively boosting the dose to hypoxic subvolumes. METHODS AND MATERIALS: A Monte Carlo model was developed that separates the tumor into two compartments, one of which receives a primary dose, and one of which receives a higher boost dose. During radiation delivery, each compartment consists of three clonogen subpopulations: those that are well oxygenated, those that are temporarily hypoxic (geometrically transient hypoxia), and those that are permanently hypoxic (geometrically stable hypoxia). The spatial location of temporary hypoxia within the tumor volume varies over time, whereas, the spatial location of permanent hypoxia does not. The effect of reoxygenation was included. Clonogen proliferation was not included in the model. RESULTS: A modest boost dose (120%-150% of the primary dose) increases tumor control probability to that found in the absence of permanent hypoxia. The entire hypoxic subvolume need not be included to obtain a significant benefit. However, only tumors with a geometrically stable hypoxic volume will have an improved control rate. CONCLUSIONS: Tumors with an identifiable geometrically stable hypoxic volume will have an improved control rate if the dose to the hypoxic volume is escalated. Further work is required to determine the spatiotemporal evolution of the hypoxic volumes before and during the course of radiotherapy.

Algorithms↗