Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes.

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (µs') at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation delivery.

This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements.

Dosimetric evaluation of parallel opposed spatially fractionated radiation therapy of deep-seated bulky tumors.

Application of a single fraction of parallel opposed GRID beams as a means of increasing the efficiency of radiation delivery to deep-seated tumors has been investigated. This evaluation was performed by measurement of dosimetric characteristics of the GRID radiation field in parallel opposed and single beam geometry. The limitations of the parallel opposed technique in terms of field size and tumor thickness have been evaluated for the conditions of acceptable spatial modulation. The results of this investigation have demonstrated an increase in therapeutic advantage for the parallel opposed technique over the single beam method when treating a deep seated tumor.

Dosimetric validation of the MCNPX Monte Carlo simulation for radiobiologic studies of megavoltage grid radiotherapy.

PURPOSE: To validate the MCNPX Monte Carlo simulation for radiobiologic studies of megavoltage grid radiotherapy. METHODS AND MATERIALS: EDR2 films, a scanning water phantom with microionization chamber and MCNPX Monte Carlo code, were used to study the dosimetric characteristics of a commercially available megavoltage grid therapy collimator. The measured dose profiles, ratios between maximum and minimum doses at 1.5 cm depth, and percentage depth dose curve were compared with those obtained in the simulations. The simulated two-dimensional dose profile and the linear-quadratic formalism of cell survival were used to calculate survival statistics of tumor and normal cells for the treatment of melanoma with a list of doses of the fractionated grid therapy. RESULTS: A good agreement between the simulated and measured dose data was found. The therapeutic ratio based on normal cell survival has been defined and calculated for treating both the acute and late responding melanoma tumors. The grid therapy in this study was found to be advantageous for treating the acutely responding tumors, but not for late responding tumors. CONCLUSIONS: Monte Carlo technique was demonstrated to be able to provide the dosimetric characteristics for grid therapy. The therapeutic ratio was dependent not only on the single alpha/beta value, but also on the individual alpha and beta values. Acutely responding tumors and radiosensitive normal tissues are more suitable for using the grid therapy.

Dosimetric characteristics of a newly designed grid block for megavoltage photon radiation and its therapeutic advantage using a linear quadratic model.

Grid radiation therapy with megavoltage x-ray beam has been proven to be an effective technique for management of large, bulky malignant tumors. The clinical advantage of GRID therapy, combined with conventional radiation therapy, has been demonstrated using a prototype GRID block [Mohiuddin, Curtis, Grizos, and Komarnicky, Cancer 66, 114-118 (1990)]. Recently, a new GRID block design with improved dosimetric properties has become commercially available from Radiation Product Design, Inc. (Albertive, MN). This GRID collimator consists of an array of focused apertures in a cerrobend block arranged in a hexagonal pattern having a circular cross-section with a diameter and center-to-center spacing of 14.3 and 21.1 mm, respectively, in the plane of isocenter. In this project, dosimetric characteristics of the newly redesigned GRID block have been investigated for a Varian 21EX linear accelerator (Varian Associates, Palo Alto, CA). These determinations were performed using radiographic films, thermoluminescent dosimeters in Solid Water phantom materials, and an ionization chamber in water. The output factor, percentage depth dose, beam profiles, and isodose distributions of the GRID radiation as a function of field size and beam energy have been measured using both 6 and 18 MV x-ray beams. In addition, the therapeutic advantage obtained from this treatment modality with the new GRID block design for a high, single fraction of dose has been calculated using the linear quadratic model with alpha/beta ratios for typical tumor and normal cells. These biological characteristics of the new GRID block design will also be presented.